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Antiretroviral therapy adherence and retention in care in middle-income and low-income countries: Current status of knowledge and research priorities
Abstract
Adherence to combination antiretroviral therapy (cART) is one of the most important contributing factors to positive clinical outcomes in patients with HIV, and long-term retention of patients in low-income and middle-income countries is emerging as an important issue in rapidly expanding cART programs. This review presents recent developments in both treatment adherence and retention of patients in low-income and middle-income countries.
Adherence is among the most modifiable variables in treatment, but there still is no 'gold standard' measurement. Best estimates demonstrate that adherence in resource-limited settings is equal or superior to that in resource-rich settings, possibly due to focused efforts on support groups and community acceptance of adherence behaviors. However, long-term data show that sustained efforts to ensure high cART adherence and evidence of intervention effects are critical, but that resource-intensive interventions are not warranted in settings where cART adherence is high. Furthermore, well conducted evaluation of culturally sensitive interventions to maximize pre-cART and post-cART initiation retention is badly needed in low-income and middle-income settings.
Further research is needed to identify risk factors and to improve adherence and retention among children, adolescents, and adults through use of social networks or emerging technologies for patients at risk for poor adherence.
... This has led to drug resistance, HIV disease progress, and increasing mortality (Kiwanuka et al., 2018;Linnemayr et al., 2017). Ensuring strict adherence to ART regimens remains a formidable challenge in SSA (Martin & Upvall, 2016;Nachega et al., 2010;Van der Kop et al., 2013). Figure 1 shows the percentage of adults and children on ART in selected countries in SSA. ...
... It is important to note that there many factors that affect adherence to ART including forgetting doses, being aware from home, changes in daily routines, lack of interest to take medications, alcohol use, and lack of clear information on medications (Kim et al., 2015). Research has shown that treatment adherence is one of the most important predictors of treatment effectiveness, viral suppression of HIV replication, ART drug resistance, and disease progression (Axelsson et al., 2015;Fox et al., 2016;Nachega et al., 2010). The text-messaging intervention is an emerging tool in managing people living with HIV to adhere to treatment. ...
... However, there is a lack of evidence on the benefit of DHI in the area of ART adherence. Significant challenges include the large numbers of people on ART who face economic constraints to sustained treatment access (Déglise et al., 2012;Nachega et al., 2010). On the other hand, the mobile phone network has spread rapidly throughout SSA and communications through text messages has become extremely popular. ...
BACKGROUND: Human Immunodeficiency Virus (HIV) infection is one of the most devastating human pandemics in Sub-Saharan Africa (SSA) and this is the region most hit by pandemic. Adherence to Antiretroviral Therapy (ART remains challenging and varies between 27% and 80% compared to the required level of 95%. Lack of adherence is of one the major causes of treatment failures. Given the increase in the use of mobile phones in Africa, text messaging is seen as a potential strategy to improve medication adherence although there is little evidence to support this argument. The aim of this review is to evaluate the efficacy of text messaging interventions to improve adherence to antiretroviral treatment. METHODS: The Effective Public Health Practice Project (APHPP) tool was used to ensure that included Randomized Controlled Trials (RCT) studies follow vigorous methodological standards including selection bias, study design, confounders, blinding, data collection methods, and withdrawal and dropout. Selected bibliographic databases MEDLINE, Web of Science, and CINAHL Plus were searched for relevant articles published in English and dated between 2005 and 2018. Six trials met the inclusion criteria as set out in the protocol. Due to the inconsistency and the likely observed heterogeneity, narrative synthesis of evidence was carried out. RESULTS: The results from 2/3 of included studies provided evidence that text messages reminders improve adherence to antiretroviral treatment whereas 1/3 produced contradictory results. Nevertheless, weekly Short Messaging Service (SMS) reminders were more effective than daily (SMS) in achieving 95% self-reported adherence to antiretroviral treatment and in reducing the frequency of treatment interruptions. The results indicated that patients receiving text messages had their plasma HIV viral load suppressed, median CD4+ cell counts increased and were on 100% on time picking up monthly ART refills compared to the control. CONCLUSION: Included studies in this review provided evidence that simple SMS reminders were important in improving and sustaining optimal ART adherences. Text messaging is seen as potential strategy to improve medication adherence. Therefore, it should be included in health systems strategies to help improve sustainable development goals. The results suggest that preventing treatment failure can be achieved by SMS reminders in a resource limited setting.
... Consistently high to almost perfect levels of optimal adherence (between 70% and the standard benchmark of 95% ART doses) are required to prevent drug resistance, disease progression and achieve viral suppression (Nachega et al., 2010b;Paterson et al., 2000). Optimal ART adherence refers to taking medication as prescribed by the healthcare provider and attending clinic appointments and pharmacy refills as scheduled (Vreeman et al., 2014). ...
... Pill count adherence is the percentage of medications dispensed that are taken by the patient. This process-oriented measure is based on recommended cutoffs for the percentage of adherence, that is, optimal adherence at >95% adherence and non-adherent if adherence is less than or equal to 95% (Nachega et al., 2010b). The cutoff for adherence was 95% in 6 studies, and 90% in one study (Table 1). ...
... Most treatment supporters are community health workers (CHW), friends, community, and family members. This finding not only aligns with UNAIDS' current focus on investing in communities to make a difference in the fight against HIV, but also highlights the importance of family and community based informal relationships of support and underscores the value of patient's respect and trust in ensuring the effectiveness of TSIs (Kunutsor et al., 2011;Nachega et al., 2010b;UNAIDS, 2019). Trusted family and community-based relationships of support are associated with patient autonomy and improved treatment self-efficacy (Kredo et al., 2013). ...
This systematic review and meta-analysis evaluated the effectiveness of treatment supporter interventions (TSI) in improving ART adherence and viral suppression among adults living with HIV (PLWH) in sub-Saharan Africa. This review included ten randomized controlled trials (RCT) and six cohort studies comparing treatment support interventions to the standard of care (SOC). Primary outcomes include pill count ART adherence and viral load suppression (VLS). Pooled relative risk ratios (PRR) with 95% confidence intervals were generated using random-effects models. Stratified analyses and meta-regressions were conducted to determine the effect of study type, follow-upperiod, and patient treatment supporters on ART adherence. Treatment supporters included partners, friends, family members, trained community health workers, and HIV positive peers. TSIs were associated with a 7.6% higher ART adherence compared to the SOC group (PRR = 1.076, [95% CI = 1.005, 1.151]). VLS was 5% higher in the treatment group compared to the SOC group (PRR = 1.05, [95% CI = 1.061, 1.207]). There was a significant, positive association between TSIs and VLS in community-based delivery settings but not in facility-based settings. TSIs were statistically significant for VLS in cohort study designs (RR = 1.073, [95% CI = 1.028, 1.121]) but not in RCTs. Findings suggest that TSIs critical in facilitating optimal ART adherence and VLS among PLWHs.
... and are similarly prone to the claim that they may be unable to sustain adherence to treatment, and therefore experience inferior treatment outcomes in relation to other groups. These accusations may be linked to assumptions about pre-or post-migration stresses [11], treatment interruptions [12] during previous episodes of forced displacement, and the inherent hardships [13] of life in asylum. These arguments are disputed by advocates who invoke human rights principles such as access to essential medicines [ 14], humanitarian law that instructs States to provide refugees with a standard of public relief equivalent to what is received by host nationals [15,16], and the demonstrated feasibility of delivering HAART to similar groups [17,18]. ...
... The original and backwards-translated English versions were reconciled prior to pre-testing and pilot-testing. Key self-reported adherence measures included a retrospective four-day dose-by-dose recall [12] and a retrospective one-month general recall measured on a visual analogue scale (VAS) [13]. Adherence to pharmacy refill schedule was assessed using a pharmacy-based measure of HAART prescription refills and calculated as the proportion of prescribed refills collected divided by the total required refills up to 24 months prior to the interview date. ...
... In studies of refugees who have been resettled. virological outcomes were also good (12)(13)(14)(15)(16). In sub-Saharan African HIV treatment programmes as a whole. ...
In response to a major gap in evidence regarding treatment outcomes among asylum-based refugees. the primary objective of the thesis was to investigate adherence to highly active antiretroviral therapy (HAART) and virological outcomes among refugees and to compare these outcomes with local host communities in one urban, Southeast Asia setting (Sungai Buloh, Kuala Lumpur, Malaysia) and one remote sub-Saharan refugee camp (Kakuma. Kenya) setting. Given limited resources for expanding treatment, questions have been raised as to whether refugees can achieve sufficient levels of adherence and viral suppression to justify sustaining and expanding access. Data sources included a structured questionnaire with self-reported adherence measures, a pharmacy-based prescription refill measure, HIV viral loads, and indepth interviews. Analyses made use of quantitative and qualitative approaches. The thesis begins by presenting the rationale, aims, research questions, and a description of preparatory work. Paper One presents the results of a systematic review of the literature on adherence to HAART and treatment outcomes among conflict-affected and forcibly displaced populations. finding only 17 reports, five of which included less than <100 clients, adherence estimates in the range of 87-99.5%, and good treatment outcomes. Papers Two and Three present the quantitative findings from both settings, finding no differences in outcomes between refugees and the host community in either setting, but a large difference between the settings. In Malaysia, 83% of clients on HAART for 2:25 weeks were suppressed while only II % were suppressed in Kenya. Female sex, longer time from HIV diagnosis to HAART start, and optimal adherence pharmacy refill schedule were protective in the Malaysian setting while temporary migration for 2: I month (in the previous year) and 2: I hour average transit time to clinic were independent risk factors. Larger household sizes were protective in the Kenyan setting. Paper Four offers an account of patient experiences based on the qualitative findings from both settings, and suggests that systemic barriers and resilient strategies were prevalent in both settings; however. intensive systemic barriers appeared to overwhelm personal resilience in the camp setting. Paper Five positions the work in the context of previous and future research and makes recommendations for programs and policy. The thesis concludes by suggesting that. just as good treatment outcomes were shown to be achievable in a range of forcibly displaced groups. asylum-based refugees were also capable of treatment success and maintain outcomes similar to those of the host communities. There is a clear public health and humanitarian interest in guaranteeing access to ART, promoting optimal adherence. and sustaining viral suppression in all who are in need of treatment. When problems in achieving and sustaining viral suppression occurred, they were not typically due to previous forced displacement, or refugee status itself. Overall, refugees ought to have equal access to HIV treatment based on the principles of fairness, human rights, and individual and population-based public health benefits. Since HIV-positive individuals on HAART with good adherence will rarely transmit HIV to their sexual partners, it is in the enlightened self-interest of host country governments to support HIV programs that serve HIV -positive refugees and host clients equally.
... Other factors which were statistically insignificant in this study were; ethnicity, religion, marital status, level of education, living condition and source of support. Although in some studies association between marital status and adherence levels were also not established, in Zambia unmarried people were found more non-adherent [8,10,11]. Similarly, some studies did not yield any association between education level and adherence levels, but others have documented significance [8,10,12,13]. Pertaining to source of support, it is highlighted that there was a significant association between availability of social support in taking ARV treatment and adherence to treatment in Ethiopia [8]. ...
... Although in some studies association between marital status and adherence levels were also not established, in Zambia unmarried people were found more non-adherent [8,10,11]. Similarly, some studies did not yield any association between education level and adherence levels, but others have documented significance [8,10,12,13]. Pertaining to source of support, it is highlighted that there was a significant association between availability of social support in taking ARV treatment and adherence to treatment in Ethiopia [8]. ...
... Other studies have also concurred that depression is associated with non-adherence [8]. The association between emotional status particularly depression and non-adherence is further re-iterated elsewhere [10]. ...
... 11 Despite reportedly high levels of adherence to antiretroviral therapy (ART) globally (>95%), diminishing adherence levels over time remains a concern, primarily the loss of patients during scaling up of HIV programmes. 12 Evidence-based strategies to mitigate adherence challenges for individuals on HIV treatment include facility and community-based interventions, which includes individual or group adherence counselling, pharmacist counselling and medication fast-tracking, mHealth, home-based/community-based strategies, financial incentives, nutritional support, motivational interviewing and awarding of disability grants. 13 Individual counselling, peer-led support groups and different models of group adherence counselling interventions, such as teen clubs, are the most common interventions for ALHIV. ...
... The literature search will be guided by the following inclusion criteria: 1. Published studies in peer-reviewed journals and grey literature. 2. The study population includes ALHIV aged [10][11][12][13][14][15][16][17][18][19] years, both perinatally and behaviourally infected adolescents included. 3. Reported the association between the intervention, and viral suppression, retention and adherence. ...
Introduction
Adolescents represent one of the most underserved population groups among people living with HIV. With successes in the elimination of mother to child transmission initiatives and advances in paediatric HIV treatment programmes, a large population of HIV-infected children are surviving into adolescence. Adolescence presents unique challenges that increase the risk of non-suppressed viral loads in adolescents living with HIV (ALHIV). There is a need to develop, implement and test interventions to improve viral suppression among ALHIV. Systematic reviews of recent studies present scarce and inconclusive evidence of effectiveness of current interventions, especially for adolescents. This protocol provides a description of a planned review of interventions to improve treatment outcomes among unsuppressed ALHIV.
Methods and analysis
A comprehensive search string will be used to search six bibliographic databases: PubMed/MEDLINE, Sabinet, EBSCOhost, CINAHL, Scopus and ScienceDirect, for relevant studies published between 2010 and 2020 globally, and grey literature. Identified articles will be exported into Mendeley Reference Management software and two independent reviewers will screen the titles, abstracts and full texts for eligibility. A third reviewer will resolve any discrepancies between the two initial reviewers. Studies reporting on interventions to improve viral suppression, retention and adherence for adolescents will be considered for inclusion. The systematic review will be performed and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols. Where feasible, a meta-analysis will be conducted using Stata Statistical Software: Release V.16. The quality of the studies and risk of bias will be assessed using the Critical Appraisal Skills Programme checklists and Risk of Bias in Non-randomised Studies of Interventions tool, respectively.
Ethics and dissemination
The systematic review entails abstracting and reviewing already publicly available data rather than any involvement of participants, therefore, no ethical clearance will be required. Results will be shared with relevant policy-makers, programme managers and service providers, and published and share through conferences and webinars.
PROSPERO registration number
CRD42021232440.
... 24 Given its ease of implementation and use of already existing resources. [24][25][26] At this time, there are no gold standard methods for assessing adherence. 25 In the present study, the adherence of CPT by selfreported measurement was 205 (67.8%). ...
... [24][25][26] At this time, there are no gold standard methods for assessing adherence. 25 In the present study, the adherence of CPT by selfreported measurement was 205 (67.8%). This finding was consistent with those similar studies done in Uganda 65.7% 12 and the University of Gondar. ...
Purpose
This study aimed to assess the factors that affect adherence to co-trimoxazole preventive therapy (CPT) among human immunodeficiency virus (HIV)-positive adults in an antiretroviral therapy (ART) clinic at the University of Gondar Compressive Specialized Teaching Hospital (UOGCSTH).
Methods
A hospital-based cross-sectional study was conducted from March 1 to April 30, 2018, at the ART clinic at UOGCSTH. Data were collected using face-to-face interviews with pretested and standard questionnaires. Binary and multivariable logistic regression analyses were used to assess the association between different variables. P<0.05 was used to declare the association.
Results
The prevalence of adherence to CPT by self-reporting measurement was 205 (67.8%). Factors such as level of education, taking street drugs (alcohol and khat), spouse knowledge about clients on CPT, knowledge of the benefit of CPT, duration of CPT, missed dose, got proper information on how to take CPT, and counseling done on refill were found to be significantly associated with adherence to CPT.
Conclusion and Recommendations
The overall adherence to CPT was fair in our study. To improve the adherence, continuous education and counseling, giving group service support for clients and having a separate counseling room are some of the possible solutions.
... 7 Concerns have been raised about waning adherence over time, including loss of patients from HIV programmes when scaling up. 8 Recommendations for monitoring long-term retention rates, and the development of evidence-based interventions to address problems, especially among adolescents, have been put forward. 8 Namibia has adopted the fast track goals of the Joint United Nations Programme on HIV and AIDS to control the HIV epidemic by 2030. ...
... 8 Recommendations for monitoring long-term retention rates, and the development of evidence-based interventions to address problems, especially among adolescents, have been put forward. 8 Namibia has adopted the fast track goals of the Joint United Nations Programme on HIV and AIDS to control the HIV epidemic by 2030. The fast track goals are aimed at ensuring that 90% of people living with HIV (PLHIV) are identified; 90% of those identified are effectively linked and retained on ART and that 90% of these achieve viral suppression. ...
Background:
Adolescents living with HIV (ALHIV) are notably underserved by the national HIV programmes globally because of their unique needs. Of particular concern is limited access to and availability of adolescent-friendly antiretroviral therapy (ART) services, which contribute to poor retention in care in many sub-Saharan African countries. A Teen Club intervention was introduced in 2010 in Windhoek, Namibia, to improve retention in care among ALHIV through psychosocial support in a peer-group environment.
Objectives:
To compare the effects of the Teen Club intervention against standard care on retention in HIV care amongst adolescents at a Paediatric ART clinic.
Method:
A retrospective cohort analysis of adolescents aged 10-19 years receiving ART between July 2015 and June 2017 was conducted. Routine patient data were extracted from an electronic database and patient registers. A sample of 385 participants was analysed: 78 in the Teen Club and 307 in standard care. Retention was measured by assessing attendance to prescribed clinic visits up to 24 months. Comparisons were assessed with the Chi-square test, and Kaplan-Meier survival analysis was conducted to analyse differences in retention rates.
Results:
The overall retention rate at 24 months among all adolescents was 90.1%, with no statistically significant difference between those in Teen Club (91%) and those in standard care (89%) (p = 0.956). Younger adolescents (10-14 years) had better retention rates at 24 months compared to older adolescents (15-19 years) (94% vs. 86%; p = 0.016). Retention rates were significantly higher for adolescents on first-line ART regimen (vs. second line: hazard ratio [HR] = 0.333; 95% confidence interval [CI] = 0.125-0.889); on ART ≥ 12 months (vs. < 12 months: HR =0.988; 95% CI = 0.977-0.999); and those to whom their HIV status was disclosed (HR = 0.131; 95% CI = 0.025-0.686).
Conclusion:
Group-based adherence support interventions did not improve retention rates for younger adolescents in specialised paediatric ART clinics but may still hold the potential for improving retention rates of older adolescents.
... With money, PLHIV are able to meet routine transport costs and ensure food security and access to medicines amid stockouts, which are highlighted as significant barriers to ART adherence in Africa. 6,19,21,22,34 Using money, clients are able to manage uncertainty and ensure their continuation on treatment. Access to adequate monetary resources further helps to neutralize the effects of unfavorable treatment arrangements and stigma on the attainment/protection of valued goals in life like privacy and dignity and marriage and intimacy. ...
... The study affirms that structural barriers such as fears of stigma, poverty, and health-system limitations remain key constraints to ART adherence and therefore realizing its primary benefit of normalizing life as shown in previous studies. 3,4,6,28,34 In addition, this study shows that structural barriers increase the financial and psychosocial costs of normalizing life while on free ART. It is evident that several PLHIV managed to overcome the barriers to adhere to ART, protect privacy and anonymity, and sustain intimate relationships. ...
Antiretroviral therapy (ART) is considered the treatment that enables people living with HIV (PLHIV) to lead a “normal life”. In spite of the availability of free treatment, patients in resource-poor settings may continue to incur additional costs to realize a normal and full life. This article describes the monetary expenses and psychosocial distress people on free ART bear to live normally. We conducted in-depth interviews with 50 PLHIV on ART. We found that the demands of treatment, poverty, stigma, and health-system constraints interplay to necessitate that PLHIV bear continuous monetary and psychosocial costs to realize local values that define normal life. In the context, access to free medicines is not sufficient to enable PLHIV in resource-poor settings to normalize life. Policy makers and providers should consider proactively complementing free ART with mechanisms that empower PLHIV economically, enhance their problem-solving capacities, and provide an enabling environment if the objective of normalizing life is to be achieved.
... Since 2005, ART are available free of charge in Madagascar through a national program of care for PLHIV with the support and financing from the Global Fund. However, retention in care, non-adherence and ART attrition are recognized as challenges for PLHIV care programs in Africa including Madagascar [7][8][9][10][11]. ...
... We carried out a review of the existing literature to develop and adapt a questionnaire assessing the knowledge, attitude and practice of ART in PLHIV as no standardized and validated questionnaire is available [10,16,19,[24][25][26][27][28] (Additional file 1). ...
Background
Adherence to antiretroviral therapy (ART) may be influenced by knowledge, perception and perception regarding ART. The purpose of this study was to assess knowledge, attitude/perception and practice regarding ART among people living with HIV/AIDS (PLHIV).
Methods
We conducted a cross-sectional survey to assess knowledge, attitudes, perception and practices ART in PLHIV. The survey was suggested to all PLHIV of at least 18 years old and who were on ART for at least 1 month. PLHIV who were unable to answer questions correctly and those who did not complete the survey for any reason were excluded.
Results
During the study period, 234 PLHIV were included. Participants were mostly men (75.2%). The median age was 33 years (IQR: 27–41). The median time since HIV diagnosis was 25 months (IQR: 9–56) and the median duration of ART was 18 months (IQR: 8–48). 87.6% had an overall good knowledge of ART. However, only 3.2% knew the name of their ART, 31.2% were aware that ART should be taken at a fixed time and 17.1% knew how to take ART in relation to food intake. 75.6% of participants had an overall positive attitude/perception of ART. However, 10.7% were convinced that other methods were more effective than ART for treating HIV and 42.7% thought that taking ART was shameful. The assessment of practices showed that in case of missed dose, 48.3% of participants routinely skipped this dose instead of trying to take it as soon as possible. In multivariate analysis, good knowledge of ART was independently associated with high level of education (aOR: 4.7, IC95%: 1.6–13.7, p = 0.004) and disclosure of HIV status (aOR: 2.7, IC95%: 1.1–6.6, p = 0.029).
Conclusions
This study showed an overall good knowledge and a predominantly positive attitude/perception of ART. However, accurate knowledge of ART intake was insufficient and the stigma associated with taking ART remained very present. Furthermore, very heterogeneous practices may reflect lack of instruction given by the physician regarding ART intake.
Electronic supplementary material
The online version of this article (10.1186/s12913-019-4173-3) contains supplementary material, which is available to authorized users.
... The four epidemiological evidences founded in HIV pediatric research are similar to those found in the literature [20][21][22][23] . ...
... Fault factors in routine consultations and social vulnerability are cited by several authors 21,23 . Studies in pediatric cohorts suggest that the inclusion of psychosocial interventions, care gratuity, psychotherapy, information and advice and support in relation to the caregiver are associated with better retention in care and adherence to treatment. ...
Scores to predict treatment outcomes have earned a well-deserved place in healthcare practice. However, when used to help achieve excellence in the care of a given disease, scores should also take into account organizational and social aspects. This article aims to create scores to obtain key variables and its application in the management of care of a given disease. We present a method called Epidemiological Planning for Patient Care Trajectory (PELC) and its application in a research of HIV pediatric patients. This case study is presented by means of two studies. The first study deals with the development of the method PELC. The second is HIV Pediatric case-control study based on PELC method. HIV pediatric research - the first practical PELC application - found these four key variables to the individual quality level care trajectories: adherence to ART, attending at least one appointment with the otolaryngologist, attending at least one appointment with social services, and having missed one or more routine appointments. We believe PELC method can be used in researches about any kind of care trajectories, contributing to quality level advancements in health services, with emphasis on patient safety and equity in healthcare.
... [6] Adherence to prescribed treatment regimens is a necessity for effective long-term therapy on ART. Recent studies suggest that adherence levels need to range from 70 to 90% for treatment regimens to be effective [7]. Children and adolescents living with HIV have unique barriers to achieving optimal adherence as they are often placed on ART from a very young age, and face the prospect of being on treatment for life [8]. ...
Despite improvements in HIV management, children and adolescents living with HIV remain vulnerable. Caregiver mortality in a large paediatric and adolescent HIV clinic in Johannesburg is described and the effect of the death of a caregiver on children and adolescents’ HIV treatment outcomes was investigated. We analysed retrospective longitudinal data and included children or adolescents attending the clinic between 01 January and 31 December 2021 divided into those with documented primary caregiver mortality and those without (ever documented). Viral load, treatment regimens, CD4, and anthropometry were analysed for 2021. Caregiver vital status was recorded in 1171 (93%) of the 1260 patients attending in 2021. In 115 children or adolescents (10%) we found a documented death of caregiver(s). Amongst 1120 mothers, 100 (9%) had died; of 460 fathers, 18 (4%) had died and one (1%) of 100 other caregivers had died. A large number (n = 54 [45%]) of the 119 deaths occurred between 2016 and 2021 and 66 (69%) after the child/adolescent’s enrolment in the clinic. In 2021, stunting and wasting were more common in the participants with caregiver death than those without (χ2 = 4.98, 6.64, p = 0.01 and 0.03 respectively). No significant difference was seen between the groups for viral load, treatment regimens and CD4 counts. Caregiver death was incompletely captured in the clinic database, suggesting that clinicians were unaware of the death of a caregiver. Children experiencing the death of a caregiver were more likely to be malnourished. We propose increasing attention on the wellbeing of caregivers in paediatric HIV services.
... Significant progress has been achieved in the global fight against HIV/AIDS in the last twenty years [1]. However, retention in care for children and adolescents living with HIV (CALHIV) remains a major operational challenge requiring innovation and creativity [2][3][4]. Following great success in the use of Antiretroviral Therapy (ART), larger numbers of children living with HIV are surviving into adolescence and adulthood. ...
Background: Loss to Follow-Up (LTFU) among HIV positive children and adolescents greatly contributes to sub-optimal retention in HIV prevention and treatment program outcomes. This can be worse among conflict affected areas of the country. LTFU threatens efforts to ensure longevity and survival of children and adolescents living with HIV. In the context of the ongoing socio-political crises and instability in the Northwest and Southwest Regions of Cameroon, we investigated reasons for LTFU among children and adolescents enrolled on ART. Methods: We conducted a qualitative study, nested within a larger cohort study (2018-2022) on assessing the incidence of LTFU among children and adolescents in two regions of Cameroon. The data collection was done from November 2021 to January 2022.We traced and interviewed 25caregivers of children and adolescent’s LTFU. Recorded interviews were transcribed, translated and then analyzed using Atlas-ti Version 9. Results: The following reasons were reported as the main contributing factors of LTFU: Socio-political crises/displacement, long distances/cost of transportation, lack of partner/family support, refusal/dating/marriage among adolescents, poverty/competitive life activities, stigma, shortage of ARVs/poor efficacy, alternative forms of health care and negative attitudes of healthcare providers. Conclusion: Our study found multiple factors at personal, family, community and health system levels, which contribute to poor retention of children and adolescents in HIV care with the leading reason postulated being displacements and constant roadblocks due to the current sociopolitical crises. The impact of the socio-political crisis on HIV services therefore cannot be neglected.
... Globally, it has been reported that adolescents have lower retention in care, adherence to antiretroviral therapy (ART), viral suppression, and immunological recovery rates, as well as a higher risk of virological rebound than adults. 1 Poor or nonadherence to ART is associated with virologic failure, viral rebound and drug resistance which may lead to disease progression, recurrent illnesses, and poor health outcomes. 2 The World Health Organization (WHO) recommends adolescent-friendly healthcare services that improve the accessibility, appropriateness, equity, acceptability, and effectiveness of HIV treatment for adolescents and young people living with HIV (AYPLHIV) aged 10-24 years. ...
Background
Adolescents living with HIV (ALHIV) face unique challenges that result in persistent gaps in achieving and maintaining suppressed viral load. Although effective evidence-based interventions to address treatment gaps in adolescents are readily available, health systems in resource-constrained, high HIV prevalence settings are challenged to implement them to achieve epidemic control. Here, we describe the health system responses to address the treatment gap of unsuppressed ALHIV on antiretroviral therapy in Windhoek, Namibia.
Methods
We conducted a qualitative descriptive and exploratory study in Windhoek between June and October 2023. Nineteen purposively selected key informants, ranging from pediatric HIV program managers to healthcare providers, were interviewed. In-depth interviews were audio-recorded and transcribed verbatim. The transcripts were uploaded to ATLAS.ti and subjected to thematic analysis.
Results
The four main themes elucidated challenges related to adherence and retention as well as health system responses in the form of interventions and support programs. The predominant adherence and retention challenges faced by ALHIV were mental health issues, behavioral and medication-related challenges, and inadequate care and social support. The health system responses to the identified challenges included providing psychosocial support, peer support, optimization of treatment and care, and the utilization of effective service delivery models. Key health system support elements identified included adequately capacitated human resources, efficient medication supply chain systems, creating and maintaining an enabling environment for optimum care, and robust monitoring systems as essential to program success.
Conclusion
The health system responses to address the remaining treatment gaps of unsuppressed ALHIV in Windhoek are quite varied and, although evidence-based, appear to be siloed. We recommend harmonized, multifaceted guidance, integrating psychosocial, treatment, care, and peer-led support, and strengthening client-centred differentiated service delivery models for unsuppressed adolescents.
... [4,5] The bulb possessed antiseptic, anthelmintic, antispasmodic, antiinflammatory, diuretic, carminative, expectorant, hypoglycaemic, febrifuge, lithotriptic, hypotensive, stomachic, and tonic properties [5]. Allium cepa (Onions) contain generous amounts of flavonoid quercetin that protect against cataracts, cardiovascular disease, and cancer [6,7]. Ivermectin is potently active again many of internal and external pathogens [8,9]. ...
BACKGROUND: To identify and address modifiable baseline clinical and non-clinical predictors related to negative outcomes, and identify high risk patients who need priority attention in order to prevent future failure of treatment in HIV patients. METHODS: The study was a longitudinal clinical based cohort study of One hundred and forty (140) HIV infected adults who were initially ART naive and commenced ART in June-July 2013 were followed up to June 2014. Three out of the participants were lost to follow up, one participant died and 1 participant was transferred to another treatment centre, while a total of one hundred and thirty-five (135) patients were finally included in the immuno-virologic analysis. Adherence was assessed using both self-report questionnaire and measurement of Mean Cell Volume (MCV) which was obtained using automated haematology analyzer. CD4 counts were analyzed using flow cytometry method and HIV-RNA levels were measured by using the RT-Polymerase Chain Reaction technique. RESULTS: Incomplete adherence was recorded in 28 (20.7%) of the study participants, immunologic failure (decline in CD4 count to or below baseline or CD4 count change < 50 cells/ul at 12 months) was observed in 39 (28.8%) of the participants. Virologic failure rate (viral load > 400 copies/ml) was 27.4% and immuno-virologic failure rate was 31.9%. Using logistic regression model, immunologic failure was associated with male gender (OR=1.29; p=0.008), non-disclosure of status (OR=1.24; p=0.01), baseline anaemia (OR=1.15; p=0.009) and incomplete adherence by self-report (OR=3.28; p=0.001). Virologic failure was associated with no formal education (OR=2.29; p=0.01), non-disclosure of status (OR=1.04; p = < 0.01), non-adherence (OR=2.74; p=0.015), being unemployed (OR=0.57; p=0.04). CONCLUSIONS: The study observed that immunologic recovery and virologic suppression rate within the first year of treatment was significant, although the rate of incomplete adherence obtained still needs improvement. Effort to promote social coping particularly to patients who were unemployed, re-strategizing on improving patient education and counseling especially to patients with no formal education, focusing on campaigns against stigmatization will help in addressing pre-dictors of negative immuno-virologic outcomes. Baseline HIV-RNA level should also be considered in addition to CD4 testing in order to identify virological failure and thus preventing the emergence of drug resistance in HIV/AIDS management .
... Adherence is defined as the act of consistently taking medications as prescribed [13]. In many populations especially those in the sub-Saharan Africa where HIV infections are more prevalent, adherence to ART has been a challenging mission to achieve given particular hurdles such as economic barriers, and social and clinical obstacles [10, [14][15][16]. These all inevitably contribute to inadequate viral suppression or worse, viral resistance to anti-HIV drugs. ...
HIV/ AIDS is a global pandemic and one of the most challenging; With no cure of the disease, various therapies available in form of regimens as Highly Active Anti-Retroviral Therapy (HAART) are the only way to manage the disease. Adherence to HAART is the most vital factor to ensure medication success and virologic suppression. However, adherence is faced with several barriers including adverse effects of Anti-Retroviral Therapy (ART) drugs, complexity of ART, social, cultural factors, and pill burden among others. Fixed Dose Combinations (FDC's) concept has been a well-recognised improvement in pharmacotherapy for treatment of a variety of chronic maladies like hypertension, diabetes, HIV/AIDS, and several FDC products consisting of HIV drugs are approved. This writing reviews the concept of adherence to ART, its barriers while stressing pill burden as a significant one which we suggest would be solved by use Fixed Dose Combinations (FDCs).
.
... Respondents who poor access missed doses thus poor adherence. Similar results were reported in a study carried out in Ethiopia where limited availability and accessibility to antiretroviral medications and health care facilities for diagnosis was responsible for poor adherence to ART treatment [39][40][41][42][43][44]. ...
... Drug relation factors associated with adherence to ARV treatment among adolescents Availability of the drugs A study carried out in middle-and low-income countries about antiretroviral therapy adherence and retention showed that availability of drugs is influenced by structural factors that may not be directly related to patient or medication [46]. Biadggilign et al. [47] in a study carried out in Ethiopia found out that limited availability and accessibility to antiretroviral medications and health care facilities for diagnosis was responsible for poor adherence to ART treatment. ...
Some factors that are related to adherence to ARV treatment among adolescents are gender, age, marital status, Education, place of residence, family size and religion. Drug related factors that are related to adherence to ARV treatment among adolescents include having all the drugs they are supposed to take, challenges faced with the drugs, Frequency of taking ARV pills in a day, challenges faced when taking ARVs and accessibility to ARV drugs. Health related factors that are related to adherence to ARV treatment among adolescents are getting routine education and counseling about adherence to ARVs, source of information, had nearby health care facility to pick ARV drugs, distance between health facility and respondents' home, availability of ARV on appointment day, availability of health care workers for ARV services.
... [4,5] The bulb possessed antiseptic, anthelmintic, antispasmodic, antiinflammatory, diuretic, carminative, expectorant, hypoglycaemic, febrifuge, lithotriptic, hypotensive, stomachic, and tonic properties [5]. Allium cepa (Onions) contain generous amounts of flavonoid quercetin that protect against cataracts, cardiovascular disease, and cancer [6,7]. Ivermectin is potently active again many of internal and external pathogens [8,9]. ...
BACKGROUND: To identify and address modifiable baseline clinical and non- clinical predictors related to negative outcomes, and identify high risk patients who need priority attention in order to prevent future failure of treatment in HIV patients. METHODS: The study was a longitudinal clinical based cohort study of One hundred and forty (140) HIV infected adults who were initially ART naive and commenced ART in June- July 2013 were followed up to June 2014. Three out of the participants were lost to follow up, one participant died and 1 participant was transferred to another treatment centre, while a total of one hundred and thirty-five (135) patients were finally included in the immuno-virologic analysis. Adherence was assessed using both self-report questionnaire and measurement of Mean Cell Volume (MCV) which was obtained using automated haematology analyzer. CD4 counts were analyzed using flow cytometry method and HIV-RNA levels were measured by using the RT-Polymerase Chain Reaction technique. RESULTS: Incomplete adherence was recorded in 28 (20.7%) of the study participants, immunologic failure (decline in CD4 count to or below baseline or CD4 count change < 50 cells/ul at 12 months) was observed in 39 (28.8%) of the participants. Virologic failure rate (viral load > 400 copies/ml) was 27.4% and immuno-virologic failure rate was 31.9%. Using logistic regression model, immunologic failure was associated with male gender (OR=1.29; p=0.008), non-disclosure of status (OR=1.24; p=0.01), baseline anaemia (OR=1.15; p=0.009) and incomplete adherence by self-report (OR=3.28; p=0.001). Virologic failure was associated with no formal education (OR=2.29; p=0.01), non-disclosure of status (OR=1.04; p = < 0.01), non-adherence (OR=2.74; p=0.015), being unemployed (OR=0.57; p=0.04). CONCLUSIONS: The study observed that immunologic recovery and virologic suppression rate within the first year of treatment was significant, although the rate of incomplete adherence obtained still needs improvement. Effort to promote social coping particularly to patients who were unemployed, re-strategizing on improving patient education and counseling especially to patients with no formal education, focusing on campaigns against stigmatization will help in addressing predictors of negative immuno-virologic outcomes. Baseline HIV-RNA level should also be considered in addition to CD4 testing in order to identify virological failure and thus preventing the emergence of drug resistance in HIV/AIDS management.
... Although AIDS-related deaths decreased among all other age groups, AIDS-related mortality increased by 45% among adolescents and young people between 2005 and 2015 [5]. AYLHIV have the worst HIV outcomes compared to other age groups of people living with HIV [6][7][8][9], including high treatment disruption and drug resistance and low rates of viral suppression [10][11][12][13][14]. ...
Long-acting injectable anti-retroviral therapy (LAART) may overcome barriers to long-term adherence and improve the survival of adolescents and young people living with HIV (AYLHIV). Research on the acceptability of LAART for this age-group is limited. We asked 953 AYLHIV about their preferred (theoretical) ART mode of delivery (pill, injectable, or other) in 2017–2018, before LAART was available or known to AYLHIV in South Africa. One in eight (12%) AYLHIV preferred LAART over single or multiple pill regimens. In multivariate analyses, six factors were associated with LAART preference: medication stock-outs (aOR = 2.56, 95% CI 1.40–4.68, p = 0.002), experiencing side-effects (aOR = 1.84, 95% CI 1.15–2.97, p = 0.012), pill-burden (aOR = 1.88, 95% CI 1.20–2.94, p = 0.006), past-year treatment changes (aOR = 1.63, 95% CI 1.06–2.51, p = 0.025), any HIV stigma (aOR = 2.22, 95% CI 1.39–3.53, p ≤ 0.001) and recent ART initiation (aOR = 2.02, 95% CI 1.09–3.74, p = 0.025). In marginal effects modelling, 66% of adolescents who experienced all factors were likely to prefer LAART, highlighting the potential high acceptability of LAART among adolescents and young people living with HIV struggling to adhere and have good HIV treatment outcomes. Adolescent boys who reported high ART pill burden were more likely to prefer LAART than their female peers in moderation analyses, suggesting that LAART may be particularly important to improve treatment outcomes among male AYLHIV as they become older. Adding LAART to existing treatment options for AYLHIV, particularly higher risk groups, would support AYLHIV to attain and sustain viral suppression—the third 95, and reduce their risk of AIDS-related mortality.
... 2 Similarly, a cohort study in Southern Africa found that adolescents are less likely to adhere to ART and have lower rates of virological suppression and immunologic recovery, and a higher rate of virological rebound after initial suppression, compared to adults. 3 Low ART adherence rates have been attributed to adolescents being less informed about HIV and the benefits of adherence 4 and lacking motivation to follow instructions of the treatment regimen. 5 Evidence suggest that ALHIV may suffer from depression and anxiety symptoms, which are associated with lower adherence to ART and higher substance abuse and risky sexual behaviours. ...
Adolescents living with HIV (ALHIV) need support from family, peers and health workers to remain on antiretroviral therapy and achieve and sustain viral suppression. This paper qualitatively explores the implementation of a psychosocial support intervention (PSS) in five primary health care facilities in the Ehlanzeni district, South Africa. Data were collected through key informant interviews and focus group discussions with ALHIV on ART. Data analysis employed inductive thematic analysis. Informed consent was obtained prior to all data collection. The PSS intervention facilitated full disclosure of HIV status to adolescents, supported treatment adherence through health education, peer support, health care provider-and client relations, and quick access to health service delivery. However, COVID-19 restrictions and regulations challenged the implementation of the intervention. The PSS intervention showed promise to support adolescent's adherence and retention in care. We recommend innovative approaches to account for systemic disruptions, as evidenced by the COVID-19 pandemic.
... These findings are similar to previous findings where it was reported that non-disclosure was a major barrier in achieving ART adherence and eventually VL suppression [51][52][53][54], social economic constraints may act as a barrier for transportation to the facility for drug refills or cause the patient to fear taking medication on empty stomach due to lack of food [29,[55][56][57], relocations may lead to lost to follow up [58,59] and gender based violence [54,[60][61][62][63] may lead to psychological stress to a patient. Additionally, Health care system related barriers to ART adherence have been reported especially in resource limited settings [64]. For example Odokonyero et al. reported that healthcare infrastructure and health care work force are vital in effectiveness of a health intervention or strategy [27]. ...
Background
Intensive adherence counseling (IAC) is an intervention recommended by the World Health Organization to improve anti-retroviral therapy (ART) adherence among people living with HIV on ART with unsuppressed viral load; and in 2016, the intervention was implemented in Uganda. This study evaluated the effect and experiences of providing IAC in an urban HIV care center in Kampala, Uganda.
Methods
This was a sequential explanatory mixed-method study that compared viral load suppression during IAC implementation (intervention) to the period before IAC at Kisenyi Health centre IV. Data were abstracted from patient files and viral load register. The effect of IAC on viral load suppression and associated factors were analyzed using modified Poisson regression with robust standard errors. Using in-depth interviews and an inductive analysis approach in Atlas-ti 8. We also explored experiences of providing IAC among healthcare workers.
Results
A total of 500 records were sampled: 249 (49.8%) in the intervention period and 251 (51.2%) in the pre-intervention period. The mean age was lower during the intervention period 33.1 (± 12.0) than 36.5 (± 13.4) in the pre- intervention period, p = 0.002 . More clients were currently on Protease-based regimen in the pre-intervention period 179 (71.3%) than 135 (54.2%) in the intervention period, p ≤ 0.001. In the intervention period, all eligible clients received IAC [249/249 (100.0%)]. Overall, 325 (65.0%) received IAC and of these, 143 (44.1%) achieved viral load suppression compared to 46 (26.3%) who received regular counseling. Receiving IAC significantly increased viral load suppression by 22% (aPR 1.22, 95% CI 1.01–1.47). Clients on Protease-based regimen were less likely to suppress than those on Efavirenz or Nevirapine-based regimens (aPR 0.11, 95% CI 0.08–0.15). All the interviewed healthcare workers lauded IAC for improving ART adherence. However, patient and health care system related factors hindered adherence during IAC.
Conclusions
The full potential of IAC in achieving viral load suppression in this setting has not been reached due to a combination of the patient and health care system related factors. Provision of adequate IAC necessities and use of patient centered approach should be emphasized to obtain the maximum benefit of the intervention .
... Recent data showed that above 95% adherence to the ART regimen is required for HIV infected patients to reach full viral suppression [11][12][13], but sustaining its adherence level requires accurate and consistent monitoring activities, and this is a major challenge for sub-Saharan African countries like Ethiopia [14] In Ethiopia, 5% to 35% of PLWHIV did not adhere to the prescribed ART regimens [15][16][17][18][19][20] which is far away from the national target of HIV prevention programs [4]. Studies conducted in different settings identified socio-demographic, behavioral, disease characteristics, medication, and health systems-related factors as the common factors affecting adherence to ART regimens [15,[21][22][23][24][25][26]. ...
Background
In Ethiopia, nearly one-third of people living with human immunodeficiency viruses do not adhere to antiretroviral therapy. Moreover, information regarding non-adherence and its associated factors among adults on first-line antiretroviral therapy in Northeast Ethiopia is limited. Therefore, this study aimed to assess the level of non-adherence and its associated factors among adults on first-line antiretroviral therapy in North Shewa Zone, Amhara Regional State, Ethiopia.
Methods
A facility-based cross-sectional study was conducted on 326 participants selected by systematic random sampling technique from the five randomly selected public health facilities. Data were collected using the questionnaire adapted from the studies conducted previously and the collected data were entered into Epi data version 3.1 and exported to Stata version 14 for further analysis. Multivariable logistic regression analysis was done and an adjusted odds ratio with its corresponding 95% confidence interval was used to declare a statistical significance.
Results
The overall prevalence of non-adherence was 17.4% [95% CI: (12.8%, 21.2%)]. Patients with no formal education [AOR (95% CI) = 5.57 (1.97, 15.88)], those who did not use memory aids to take their medications [AOR (95% CI) = 3.01 (1.27, 7.11)], travel more than 10 kilometers to visit the nearby antiretroviral therapy clinics [AOR (95% CI) = 2.42 (1.22, 25.86)], those who used substance [AOR (95% CI) = 3.57 (1.86, 28.69)], and patients whose medication time interfered with their daily routine activities [AOR (95% CI) = 15.46 (4.41, 54.28) had higher odds of having non-adherence to first-line antiretroviral therapy compared to their counter groups.
Conclusion
The level of non-adherence to first-line antiretroviral therapy was 17.4%, higher compared to WHO’s recommendation. Hence, patients counseling focused on avoiding substance use, use memory aids, and adjusting working time with medication schedule are very crucial. Furthermore, the ministry of health and the regional health bureau with other stakeholders should expand antiretroviral therapy service delivery at health facilities that are close to the community to address distance barriers.
... In Uganda, estimates of the proportion of patients who reported optimal cART adherence ranged from 68% to 98% (Mills et al., 2006). Adherence rates have also been shown to decline over time in long-standing treatment programs (Nachega et al., 2010). Those who miss more than one dose of their medication in a week are already at risk of treatment failure, and thus the development of drug resistance (Hardon et al., 2006). ...
This study seeks to investigate challenges to combined antiretroviral therapy (cART) treatment adherence and treatment outcomes in Kampala, Uganda. Data was collected from a survey administered to two cohorts of patients with human immunodeficiency virus type 1 (HIV-1) receiving care and cART from the Joint Clinical Research Center (JCRC) in Kampala. Cohort I consisted of 93 individuals successfully treated on cART for a period of three years, while Cohort II consisted of 56 individuals who have experienced treatment failure with first-line cART within two years. We hypothesize that distance to the treatment facility would be a predictor of poor adherence and thus treatment failure. However, results suggested otherwise, whereby participants living more than 2 h away from their treatment facility were actually less likely to miss their daily dose of cART (OR = 0.33, p < .05), compared to those living in proximity to the treatment center. Further, high-income employment (OR = 3.82, p < .05) and partnered relationship status (OR = 4.28, p < .05) were predicted to increase the probability of missing doses. These findings may be explained by the deep-seated stigma which has remained pervasive in the lives of HIV-positive population in Kampala, even 30 years after the peak of the HIV/AIDS epidemic.
... Poor ART adherence increases the risk of viral drug resistance, limits treatment efficacy, leading to disease progression, and reduces future therapeutic options as well as increasing the risk of transmission due to unsuppressed viral replication [7]. Although reported ART adherence is high globally (>95%), concerns have been raised about waning adherence over time including loss of patients from HIV programs when scaling up [8]. Evidence-based interventions to address adherence challenges for people on ART include individual and group adherence counselling, mHealth platforms, community and home-based strategies, pharmacist counselling and monitoring, task-shifting, medication fast-tracking, nutrition support, and provision of disability grants [9]. ...
Background. Adolescents living with HIV (ALHIV) are challenged to adhere to antiretroviral therapy (ART) and achieve and maintain virologic suppression. Group-based adherence support interventions, such as adherence clubs, have been shown to improve long-term adherence in ART patients. The teen club intervention was introduced in 2010 in Namibia to improve treatment outcomes for ALHIV by providing adherence support in a peer-group environment. Adolescents who have completed the full HIV disclosure process can voluntarily join the teen clubs. The current study compared treatment outcomes of ALHIV receiving ART at a specialized paediatric HIV clinic between 1 July 2015 and 30 June 2017 in Windhoek, Namibia. Methods. A retrospective cohort analysis was conducted on routine patient data extracted from the electronic Patient Monitoring System, individual Patient Care Booklets, and teen club attendance registers. A sample of 385 adolescents were analysed: 78 in teen clubs and 307 in standard care. Virologic suppression was determined at 6, 12, and 18 months from study start date, and compared by model of care, age, sex, disclosure status, and ART regimen. Comparisons between adolescents in teen clubs and those receiving standard care were performed using the chi-square test, and risk ratios were calculated to analyze differences in ART adherence and virologic suppression. Results. The average clinician-measured ART adherence was 89% good, 6% fair, and 5% poor amongst all adolescents, with no difference between teen club members and adolescents in standard care ( = 0.277) at 3 months. Virologic suppression over the 2-year observation period was 87% (68% fully suppressed <40 copies/ml and 19% suppressed between 40–999 copies/ml), with no difference between teen club members and those in standard care. However, there were statistically significant differences in virologic suppression levels between the younger (10–14 years) adolescents and older (15–19 years) adolescents at 6 months ( = 0.015) and at 12 months ( = 0.021) and between adolescents on first-line and second-line ART regimen at 6 months ( = 0.012), 12 months ( = 0.004), and 18 months ( = 0.005). Conclusion. The teen club model delivering psychosocial support only did not improve adherence and virologic suppression levels for adolescents in a specialized paediatric ART clinic, neither were they inferior to standard care. Considering the limitations of this study, teen clubs may still hold potential for improving adherence and virologic suppression levels for older adolescents, and more robust research on adherence interventions for adolescents with higher methodological quality is required.
1. Introduction
Due to the successes in prevention of mother-to-child transmission (PMTCT) programs worldwide and advances in paediatric HIV treatment, children with HIV are surviving to reach adolescence [1]. The World Health Organization defines adolescents as children or young adults between 10 and 19 years of age [2]. Worldwide in 2018, an estimated 1.6 million adolescents between 10 and 19 years were living with HIV, with nearly 85% living in sub-Saharan Africa [3, 4]. In most sub-Saharan Africa countries, public health facilities are ill-equipped to give guidance and support for adolescents living with HIV (ALHIV) to remain engaged in care and adhere to medication regimens [5]. In 2019 alone, there were 460,000 newly infected young people between the ages of 10 to 24 years, of whom 170,000 were adolescents between 10 to 19 years [6].
Poor ART adherence increases the risk of viral drug resistance, limits treatment efficacy, leading to disease progression, and reduces future therapeutic options as well as increasing the risk of transmission due to unsuppressed viral replication [7]. Although reported ART adherence is high globally (>95%), concerns have been raised about waning adherence over time including loss of patients from HIV programs when scaling up [8]. Evidence-based interventions to address adherence challenges for people on ART include individual and group adherence counselling, mHealth platforms, community and home-based strategies, pharmacist counselling and monitoring, task-shifting, medication fast-tracking, nutrition support, and provision of disability grants [9]. For ALHIV, individual counselling, group counselling, and peer support, such as in teen clubs, have been some of the most common interventions in Namibia.
Namibia has adopted the Joint United Nations Programme on HIV and AIDS’ (UNAIDS) fast track goals to achieve HIV epidemic control by 2030. The fast track goals are aimed at ensuring that 95% of PLHIV are identified; 95% of those identified are effectively linked and retained on ART; and 95% of these achieve virologic suppression [10]. Adolescents living with HIV have unique needs and are notably underserved globally and in national responses, which negatively affects their access to ART and results in poor ART adherence and inferior treatment outcomes such as achieving and maintaining virologic suppression [11]. In Namibia, infants, children, and younger adolescents (0–14 years) reportedly had only 63% viral load suppression, and young people (older adolescents and young adults, 15–24 years old) had 60.5%, which is well below the national average suppression levels for adults on ART at 80.5% [12].
According to WHO, a maintained viral load of <1000 ribonucleic acid (RNA) copies per ml of plasma is considered evident of virologic suppression [13]. According to the 2019 Namibia National Guidelines for Antiretroviral Treatment, virologic status is classified into three categories, namely, fully suppressed (<40 copies/ml), suppressed (40–999 copies/ml), and unsuppressed (≥1000 copies/ml). The aim of this classification is for earlier identification of patients having suboptimal responses to therapy, whose immunologic and clinical responses may not have deteriorated at this stage, but persistently have viral loads of above 40 copies/ml. These patients undergo different clinical management, which includes intensive adherence counselling and support to achieve full suppression and avoid treatment failure that may necessitate switching to a second-line ART regimen [14].
A teen club intervention was established in 2010 at a paediatric HIV clinic, in Windhoek, to address unique needs of adolescents on HIV treatment [15]. The teen club aims to improve ART adherence through, among other activities, psychosocial support, HIV counselling, and health education. In 2010, teen club interventions were introduced at health facilities in Malawi to provide ALHIV on ART with dedicated clinic time, peer mentorship, sexual and reproductive health education, ART refill and support for positive living, and treatment adherence. An evaluation of the program in 2015 found that ALHIV with no teen club exposure were less likely to be retained than those with teen club exposure (adjusted odds ratio (aOR) 0.27; 95% CI 0.16, 0.45). ALHIV aged 15–19 years were more likely to have attrition from care than those aged 10–14 years (aOR 2.14; 95% CI 1.12, 4.11) [16]. Another evaluation in Malawi of a similar teen club intervention reported in 2019 on adherence levels between younger and older adolescents and male and female adolescents found that older adolescence were associated with higher odds of optimal adherence compared to younger adolescents (aOR 1.48; 95% CI 1.16–1.90, < 0.01) [17]. Evaluations of teen clubs have been scarce, and both Malawi studies recommended age-specialized programming for adolescents and argued that more prospective research is required with higher methodological quality.
To date, the effectiveness of the teen clubs on adolescents’ ART adherence has not been formally evaluated in Namibia. This paper reports on the effects of the teen club intervention against standard care on ART adherence and virologic suppression amongst adolescents at the clinic. Table 1 shows services provided in standard care compared to the teen club. The main difference between standard care and the teen club is that the teen club provides a group-based psychosocial support platform, which meets outside of the routine clinic visits schedule to share experiences, deliver presentations, engage in educational activities, to keep the adolescents engaged in care and on ART, and improve their overall we-being.
Model of care
Similarities between teen club and standard care
3 monthly clinical visits except in high viral load patients who may be enrolled in monthly adherence counselling
Adolescents should have full disclosure by age 10–12; disclosure can be delayed depending on the cognitive ability of the adolescent
Goal-related transition from paediatric/adolescent to adult HIV services
Routine viral load monitoring and targeted viral load monitoring for suspected treatment failure
Age-appropriate and developmentally appropriate adherence counselling
Lost to follow-up/defaulter tracking and tracing
HIV treatment literacy training of guardians and caregivers on treatment adherence, disclosure, and stigma issues
Age-appropriate psychosocial support includes individualized counselling on issues such as treatment failure counselling, opportunistic infections, STIs, sexual and reproductive health, alcohol use and abuse, mental health, child protection, and other topics according to the adolescents’ needs
Routine discussion with the child on their experience at school and future plans
Linkage to relevant stakeholders and social support mechanisms in the community
Additional considerations and support in teen clubs
Adolescents should have full disclosure; this is a prerequisite for enrolment into the teen club; adolescents can enroll once disclosed to
In addition to age-appropriate psychosocial support offered in standard care, the teen club
Meets once a month on a Friday or Saturday in “safe spaces” at the clinic
Share challenges, fears, experiences, and coping mechanisms during monthly meetings
Have special talks or presentation of ALHIV-related topics from subject matter experts
Have access to information, education, and communication materials such as videos and dramas/acts on adolescence and HIV and have discussions thereafter
Occasionally participate in teen club retreats and trips where recreational activities and life stories are shared
... This possibility is particularly important in the context of the large impact of HIV-related mortality in this area , and the relationship between social support and antiretroviral therapy elsewhere (Nachega et al., 2010). ...
Background
Several theories seek to explain how social connections and cognitive function are interconnected in older age. These include that social interaction protects against cognitive decline, that cognitive decline leads to shedding of social connections and that cognitive decline leads to increased instrumental support. We investigated how patterns of social contact, social support and cognitive health in rural South Africa fit with these three theories.
Method
We used data from the baseline of "Health and Aging in Africa: a Longitudinal Study of an INDEPTH community in South Africa" (HAALSI), a population-based study of 5059 individuals aged ≥ 40 years. We evaluated how a range of social connectedness measures varied by respondents' cognitive function.
Results
We found that respondents with lower cognitive function had smaller, denser social networks that were more local and more kin-based than their peers. Lower cognitive function was associated with receipt of less social support generally, but this difference was stronger for emotional and informational support than for financial and physical support. Impairment was associated with greater differences among those aged 40-59 and those with any (versus no) educational attainment.
Conclusions
The patterns we found suggest that cognitively impaired older adults in this setting rely on their core social networks for support, and that theories relating to social connectedness and cognitive function developed in higher-income and highereducation settings may also apply in lower-resource settings elsewhere in the world.
... Studies show that the magnitude of ART treatment failure in Ethiopia ranges from 4.1% [4] to 19.8% [5]. Antiretroviral treatment fails for a variety of reasons most importantly non-adherence to antiretroviral treatment [6] which is higher in low and middle income countries [7]. Other factors that can contribute to treatment failure include antagonism between some drug combinations, degree of CD4 status before treatment initiation [8], presence of co-infection, type of treatment regimen, body mass index (BMI) [9], old age [10] and other socio economic factors. ...
Background Antiretroviral treatment (ART) is aimed for complete suppression of viral replication but it fails for a variety of reasons. The aim of this study was to determine the prevalence and associated factors of treatment failure among people on first line ART in Amhara region, North east Ethiopia.
Methods A cross sectional study was conducted from March, 2018 to July, 2018. Questionnaire survey using a pre-structured questionnaire was taken focusing on demographic data and possible risk factors of antiretroviral treatment failure. Clinical history including baseline characteristics was extracted by reviewing medical records using data abstraction sheet and data was analyzed using STATA version 14.
Results A total of 640 clients of all age from 16 health facilities were enrolled in the study. The overall antiretroviral treatment failure was 16.45% from which clinical, immunologic and virologic failure were 0.47%, 13.59% and 3.13% respectively. The viral suppression was 91.09%, but more than half, 29 (50.88%) study participants with high first viral load (>1000copies/ml) were defaulted and not tested for the 2 nd viral load testing. Binary and multivariable logistic regression analysis showed significance association of treatment failure with age at treatment initiation (OR, 1.029), duration on ART (OR, 0.87) and adherence (AOR, 4.22). High proportion of treatment failure was also found in females (62.75%) and in those below primary education (76.47%).
Conclusions In conclusion increased viral suppression is observed but the rate of default during 3 month of enhanced adherence counseling is high. The overall magnitude of treatment failure in Amhara region is 16.45%. Fair/poor adherence, older age at treatment initiation and shorter duration on ART are significantly independent factors of treatment failure. Therefore improving client follow up to adherence to treatment should be strengthened.
... Adolescents and youth, 10 to 24 years of age, represent a growing proportion of people living with HIV around the world and have worse outcomes than all other age groups [1][2][3][4][5][6]. In recent years, AIDS-related deaths among adolescents and youth increased by 50% while they have decreased among all other age groups [7]. ...
Adolescents and youth living with HIV have poorer antiretroviral treatment (ART) adherence and viral suppression outcomes than all other age groups. Effective interventions promoting adherence are urgently needed. We reviewed and synthesized recent literature on interventions to improve ART adherence among this vulnerable population. We focus on studies conducted in low- and middle-income countries (LMIC) where the adolescent and youth HIV burden is greatest. Articles published between September 2015 and January 2019 were identified through PubMed. Inclusion criteria were: [1] included participants ages 10–24 years; [2] assessed the efficacy of an intervention to improve ART adherence; [3] reported an ART adherence measurement or viral load; [4] conducted in a LMIC. Articles were reviewed for study population characteristics, intervention type, study design, outcomes measured, and intervention effect. Strength of each study’s evidence was evaluated according to an adapted World Health Organization GRADE system. Articles meeting all inclusion criteria except being conducted in an LMIC were reviewed for results and potential transportability to a LMIC setting. Of 108 articles identified, 7 met criteria for inclusion. Three evaluated patient-level interventions and four evaluated health services interventions. Of the patient-level interventions, two were experimental designs and one was a retrospective cohort study. None of these interventions improved ART adherence or viral suppression. Of the four health services interventions, two targeted stable patients and reduced the amount of time spent in the clinic or grouped patients together for bi-monthly meetings, and two targeted patients newly diagnosed with HIV or not yet deemed clinically stable and augmented clinical care with home-based case-management. The two studies targeting stable patients used retrospective cohort designs and found that adolescents and youth were less likely to maintain viral suppression than children or adults. The two studies targeting patients not yet deemed clinically stable included one experimental and one retrospective cohort design and showed improved ART adherence and viral suppression outcomes. ART adherence and viral suppression outcomes remain a major challenge among adolescents and youth. Intensive home-based case management models of care hold promise for improving outcomes in this population and warrant further research.
... ART has improved the life expectancy of people living with HIV/ AIDS in Uganda dramatically, and a scaling up of treatment has resulted in over 72% of these Ugandans receiving ART [2][3][4][5][6][7][8]. Yet the success of these drugs is dependent on high lifelong medication adherence to achieve optimal clinical outcomes, such as slowing the progression to AIDS, lengthening survival, sustained viral suppression, and prevention of drug resistance and loss of treatment options [9][10][11][12][13][14]. Moreover, ART adherence in Uganda may be lower than previously assumed [15] and be declining over time [16,17]. ...
Background:
Many HIV-positive patients do not appropriately adhere to their antiretroviral medication (ART). This leads to higher viral loads and greater probability of HIV transmission. Present bias-a tendency to give in to short-term temptations at the expense of long-term outcomes-is a potential driver of low adherence. In this study we test a novel intervention rooted in behavioral economics that is designed to overcome present bias and increase ART adherence.
Methods/design:
We will enroll 330 HIV-positive patients at Mildmay Hospital in Kampala, Uganda, into a 2-year randomized controlled trial. Participants will be randomized to one of three groups. The first intervention group (T1, n = 110) will be eligible for small lottery prizes based on timely clinic visits and demonstration of viral suppression. Group 2 (T2, n = 110) will be eligible for the same lottery prizes conditional on high adherence measured by a medication event management system (MEMS) cap. The control group (n = 110) will receive the usual standard of care. Adherence will be measured continuously throughout the intervention period and for 12 months post-intervention to evaluate effect persistence. Surveys will be conducted at baseline and then every 6 months. Viral loads will be measured annually. Primary outcomes are whether the viral load is detectable and MEMS-measured adherence. Secondary outcomes are the log-transformed viral load as a continuous measure and a binary measure for whether the person took at least 90% of their ART pills.
Discussion:
Our study is one of the first to investigate the effectiveness of lottery incentives for improving ART adherence, and in addition, it compares the relative efficacy of using electronically measured adherence versus viral load to determine lottery eligibility. MEMS caps are relatively costly, whereas viral load testing is now part of routine clinical care in Uganda. BEST will test whether directly incentivizing viral suppression (which can be implemented using readily available clinic data) is as effective as incentivizing electronically measured adherence. Cost-effectiveness analyses of the two implementation modes will also be performed.
Trial registration:
ClinicalTrials.gov, NCT03494777. Registered on 11 April 2018.
... It is also important to note that it can also result in passing on the infection either to the unborn baby or to the breastfeeding child which results in increased morbidity and mortality among infants if they do not receive the appropriate care in time. Adherence is critical for maximal and sustained suppression of viral replication, lower destruction of CD4 cells, prevention of the development of viral resistance, promotion of immune reconstitution, retard progression of disease and decrease MTCT rates (Bangsberg, 2006;Nachega et al., 2010). ...
Background: A preliminary review of St Albert's Mission Hospital data showed 15% of HIV positive pregnant and breastfeeding women (PPBW) missed drug pickup appointments and 10% were lost to follow up. This affects Zimbabwe reaching 90% viral suppression target among those on antiretroviral therapy and increases HIV transmission risk to unborn fetus or breastfeeding infant. We determined factors associated with treatment adherence and retention in care among PPBW. Methods: We conducted a cross-sectional analytic study among PPBW receiving care at the hospital. Women were sampled consecutively on presenting for antenatal or postnatal care. We used interviewer administered questionnaire to elicit information from consenting PPBW. We obtained ethical approval and written informed consent from PPBW. Results: We interviewed 120 PPBW. The majority were breastfeeding women (60.0%). Over 95% PPBW disclosed their HIV status. The majority used this hospital because the health workers treated them with respect (66.7%), maintained client confidentiality (75.0%) and had good relations with their clients (70.8%). Skipping medication because of travel (adjusted odds ratio (AOR) 95% confidence interval (CI) 0.06 (0.005-0.79 and having an unpleasant experience while seeking care AOR (95% CI) 0.05 (0.002-0.93) were independently associated with lower medication adherence. Disclosure to avoid hiding taking medication AOR (95% CI) 22.07 (1.64-297.66 and attending this hospital because the health workers maintain confidentiality AOR (95% CI) 22.07 (1.64-297.66) were independently associated with higher retention in care. Conclusion: Health system factors play an important role in adherence and retention of pregnant and breastfeeding women attending care at this facility. 249 words
... The methods of adherence measurement includes: pharmacy refill record, pill counts, medication event monitoring (MEMs), viral load measurement, CD4 count and self-report. Because of their low cost and easy implementation selfreport and pill counts are widely used in developing country [32]. However self-report is prone to recall biases and sometimes may report exaggerated adherence and heavily depends on how the interview was made. ...
... However at yeka sub-city woreda 9 and 10 health center Addis Ababa Ethiopia due to, incomplete medication adherence is the most important factor in treatment failure and the development of resistance. Although lack of defaulter tracing on time most patient develop opportunistic infection and failure to poor quality of life [9][10][11][12][13]. It is widely agreed that in order to achieve an undetectable viral load and prevent the development of drug resistance, a person on ARV drugs needs to take at least full dose of the prescribed doses on time, but patients on ART at Yeka Sub-City Woreda 9 and 10 health center Addis Ababa Ethiopia due to unknown case they discontinue their ART follow up service and suffer for serious disease and death. ...
... 9 Até agora não existia na província de Nampula um conhecimento sistematizado sobre os determinantes de adesão terapêutica. 10 Assim, esta investigação de implementação tinha como objetivo principal melhorar o programa TARV [11][12][13][14] ...
Objetivo: avaliar a situação clínica dos pacientes em tratamento antirretroviral, as taxas de adesão e abandono e seus fatores determinantes e intervir para melhorar o programa de luta contra o vírus da imunodeficiência humana em Nampula.Tipo de estudo: investigação de implementação, descritiva mista.Local: centros de saúde distritais (10) na Província de Nampula, Moçambique.População: pacientes em tratamento antirretroviral e que abandonaram o tratamento, profissionais dos cuidados de saúde primários e praticantes tradicionais de saúde. Métodos: aplicação de inquérito a pacientes e praticantes tradicionais de saúde, entrevista semiestruturada com profissionais de saúde, discussão de grupos focais com praticantes tradicionais e consulta documental. Avaliada a linha de base nos centros de saúde alvo e controlo, foi realizada uma ação de educação para a saúde com os pacientes e com os praticantes tradicionais e de formação médica com os profissionais de saúde nos distritos alvo. Depois foram avaliados os indicadores clínicos e do programa em todos os centros de saúde.Resultados: a insegurança alimentar, discriminação e dificuldade de acesso aos serviços de saúde, contribuem para uma taxa de abandono do tratamento atingindo 50 % dos pacientes. A boa adesão verifica-se em 69 %. A ação foi realizada em cinco distritos, com 63 pacientes, 59 praticantes tradicionais e 96 profissionais de saúde. Nos distritos de ação verificámos um aumento do número de Grupos de Apoio à Aderência Comunitários e de referências aos cuidados de saúde primários e uma redução do risco de abandono do tratamento de 69 %.Conclusões: existem diversas causas de abandono da terapia antirretroviral e baixa adesão. O abandono da TARV é um problema grave em Nampula e resulta de fatores individuais, sociais e do sistema de saúde. Intervenções interdisciplinares de baixo custo na área da educação em saúde, associadas a extensão agrária, podem inverter esta situação.
... Assim, o problema do VIH continua preocupante e não existe um conhecimento sistematizado sobre os fatores determinantes de adesão terapêutica nesta população em Nampula. [8][9][10] Confrontada com esta situação, a Faculdade de Ciências de Saúde (FCS) da Universidade Lúrio propôs-se realizar um trabalho de investigação operacional, destinado a avaliar a adesão à TARV na província de Nampula e propor e implementar atividades de promoção da adesão terapêutica. Este artigo apresenta o estudo da linha de base inicial e tem três objetivos: 1) Avaliar a adesão à TARV, [11][12] nos CSP na província de Nampula; 2) Identificar os fatores associados ao abandono da TARV na perceção dos pacientes; 3) Identificar os fatores associados ao abandono da TARV na perceção dos profissionais de saúde. ...
Objectives: to evaluate antiretroviral treatment adherence rates in Nampula Province and determinants of treatment non-compliance.
Research: observational cross sectional, mixed methods.
Place: five health centers of Nampula province districts, Mozambique, 2014.
Population: patients infected by human immunodeficiency virus on antiretroviral treatment, patients who have abandoned treatment, primary health care professionals.
Methods: patients on treatment and patients who are non-compliant with therapy surveys, patients information documents (clinical files, pharmacy and statistical records) were consulted, interviews with health care professionals.
Results: antiretroviral treatment abandon rate attain 40 %. We surveyed 208 patients on treatment and 86 patients who were non-compliant with therapy, 70 % were female, between 18 and 62 years of age. The main reason for non-compliance with treatment (36 %) was stigma attached to having the infection; 58 % of all people do not have enough food, 37 % suffer from depressive ideation. Good treatment adherence (>95 % of pills are taken for the last three months) is 69 %, but 36 % of people who are adherent have a bad CD4 count and 63 % are not following the recommended treatment protocol.
Conclusions: being labelled with stigma of having human immunodeficiency virus is considered the main reason for antiretroviral treatment non-adherence, but food insecurity is also an important determinant. A treatment adherence rate of 69 % explains the high incidence of opportunistic infections (27 %). Antiretroviral treatment abandon in Nampula is a serious and complex problem due to individual, social and primary health care services determinants. It will be necessary to develop an interdisciplinary intervention with patients, families and health professionals, to reverse this situation and better treatment adherence.
... "Pre-ART" co-trimaxozole (henceforth 'prophylaxis') and ART have improved the life expectancy of people living with HIV/AIDS in Uganda dramatically, and ART scale-up has resulted in over 72% of these Ugandans receiving ART [1,[3][4][5][6][7][8]. However, the success of these drugs is highly dependent on adherence to medication and retention in care to slow the progression to AIDS; lengthen survival; sustain viral suppression; and prevent drug resistance and loss of treatment options [9][10][11][12][13][14]. ...
Background:
Studies from sub-Saharan Africa (SSA) document how barriers to ART adherence present additional complications among adolescents and young adults living with HIV. We qualitatively explored barriers to ART adherence in Uganda among individuals age 14-24 to understand the unique challenges faced by this age group.
Methods:
We conducted focus group (FG) discussions with Community Advisory Board members (n = 1), health care providers (n = 2), and male and female groups of adolescents age 14-17 (n = 2) and youth age 18-24 (n = 2) in Kampala, Uganda. FGs were transcribed verbatim and translated from Luganda into English. Two investigators independently reviewed all transcripts, developed a detailed codebook, achieved a pooled Cohen's Kappa of 0.79 and 0.80, and used a directed content analysis to identify key themes.
Results:
Four barriers to ART adherence emerged: 1) poverty limited adolescents' ability to buy food and undercut efforts to become economically independent in their transition from adolescence to adulthood; 2) school attendance limited their privacy, further disrupting ART adherence; 3) family support was unreliable, and youth often struggled with a constant change in guardianship because they had lost their biological parents to HIV. In contrast peer influence, especially among HIV-positive youth, was strong and created an important network to support ART adherence; 4) the burden of taking multiple medications daily frustrated youth, often leading to so-called 'drug holidays.' Adolescent and youth-specific issues around disclosure emerged across three of the four barriers.
Conclusions:
To be effective, programs and policies to improve ART adherence among youth in Uganda must address the special challenges that adolescents and young adults confront in achieving optimal adherence. For example, training on budgeting and savings practices could help promote their transition to financial independence. School staff could develop strategies to help students take their medications consistently and confidentially. While challenging to extend the range of services provided by HIV clinics, successful efforts will require engaging the family, peers, and larger community of health and educational providers to support adolescents and young adults living with HIV to live longer and healthier lives.
Trial registration:
ClinicalTrials.gov Identifier: NCT02514356 . Registered August 3, 2015.
... To encourage patients' adherence to ART in sub-Saharan Africa, several approaches have been used: intensified adherence counselling, reminder alarms/calendars, daily or weekly mobile phone text messages, electronic pill devices, adherence clubs and the use of treatment supporters (also called treatment buddies or medicine companions) (Church et al., 2015;Hirnschall, Harries, Easterbrook, Doherty, & Ball, 2013;Knodel, Hak, Khuon, So, & McAndrew, 2011;Kunutsor et al., 2011;Mills et al., 2014;World Health Organisation, 2004). A randomised controlled trial in South Africa, which followed participants for two years, reported better adherence and ART outcomes in the arm that had treatment supporters than the arm without them (Nachega, Mills, & Schechter, 2010). Similarly, a one year follow up randomised controlled trial in Rakai district in Uganda, among pre-ART patients, also reported less attrition from the care cascade, slower HIV-related disease progression and better quality of daily life in the arm with treatment supporters compared to the one without supporters (Nakigozi et al., 2015). ...
Background:
This study aimed to understand the relevance of treatment supporters in adherence among people living with HIV taking Anti-retroviral therapy (ART) for more than five years in Uganda.
Methods:
In-depth interviews were conducted with 50 participants (28 women and 22 men) of the Complications of Long-Term ART (CoLTART) cohort with experience of at least five years on ART in Uganda. Participants were stratified by line of ART regimen and viral loads of less or above 1000 copies/ml. Data were analyzed thematically.
Results:
Many participants felt that a treatment supporter was most useful at the beginning of therapy before individuals get used to the drugs or when they are still weak. However, this did not reflect treatment outcomes, as many individuals without treatment supporters had failed on first line ART regimens and were switched to second line ART. Those who were still on first line had viral loads of ≥1000 copies/ml. There was a preference for female treatment supporters, many of who were persistent in their supportive role.
Conclusion:
Treatment supporters remain important in adherence to long-term ART. HIV-care providers need to encourage the involvement of a treatment supporter for individuals taking ART long-term.
... The fishing occupation itself includes frequent mobility, irregular work schedules, and an inconsistent cash-based income that varies based on seasonal fish yields [36,[49][50][51], all of which are likely to affect men's care engagement. Finally, factors within the broader health system (e.g., drug stock out, quality of care, human resource availability and training), and societal-level policies affecting ART eligibility [18,22,[52][53][54][55][56][57][58] have also been shown salient in their impact on access to care in SSA more broadly. ...
This cross-sectional study assessed determinants of HIV clinic appointment attendance and antiretroviral treatment (ART) adherence among 300 male fisherfolk on ART in Wakiso District, Uganda. Multi-level factors associated with missed HIV clinic visits included those at the individual (age, AOR = 0.98, 95% CI 0.97–0.99), interpersonal (being single/separated from partner, AOR: 1.25, 95% CI 1.01–1.54), normative (anticipated HIV stigma, AOR: 1.55, 95% CI 1.05–2.29) and physical/built environment-level (travel time to the HIV clinic, AOR: 1.11, 95% CI 1.02–1.20; structural-barriers to ART adherence, AOR: 1.27, 95% CI 1.04–1.56; accessing care on a landing site vs. an island, AOR: 1.35, 95% CI 1.08–1.67). Factors associated with ART non-adherence included those at the individual (age, β: − 0.01, η2 = 0.03; monthly income, β: − 0.01, η2 = 0.02) and normative levels (anticipated HIV stigma, β: 0.10, η2 = 0.02; enacted HIV stigma, β: 0.11, η2 = 0.02). Differentiated models of HIV care that integrate stigma reduction and social support, and reduce the number of clinic visits needed, should be explored in this setting to reduce multi-level barriers to accessing HIV care and ART adherence.
... Sustained adherence to HIV treatment in Uganda and other parts of sub-Saharan Africa is indicated to be primarily constrained by structural and health system related barriers. In their review of the status of knowledge and research priorities on ART adherence and retention in care in low and middle income countries Nachega and colleagues [11] observe that while HIV patients worldwide encounter social, economic and individual barriers to adherence; structural factors are the most important in resource limited settings. They refer to a systematic review of patient reported barriers and facilitators in developed and developing countries [12] which identifies cost, non-disclosure, the fear of being stigmatized, alcohol abuse, transportation difficulties and pharmacy stock-outs as the most important and frequently cited barriers to adherence in developing countries. ...
Background
Despite the national roll-out of free HIV medicines in Uganda and other sub-Saharan African countries, many HIV positive patients on antiretroviral therapy (ART) are at risk of non-adherence due to poverty and other structural and health system related constraints. However, several patients exhibit resilience by attaining and sustaining high levels of adherence amid adversity. Social capital, defined as resources embedded within social networks, is key in facilitating resilience but the mechanism through which it operates remains understudied. This article provides insights into mechanisms through which social capital enables patients on ART in a resource-poor setting to overcome risk and sustain adherence to treatment.
Methodology
The article draws from an ethnographic study of 50 adult male and female HIV patients enrolled at two treatment sites in Uganda, 15 of whom were followed-up for an extended period of six months for narrative interviews and observation. The patients were selected purposively on the basis of socio-demographic and treatment related criteria.
Findings
Social capital protects patients on ART against the risk of non-adherence in three ways. 1) It facilitates access to scarce resources; 2) encourages HIV patients to continue on treatment; and 3) averts risk for non-adherence.
Conclusions
Social capital is a key resource that can be harnessed to promote resilience among HIV patients in a resource-limited setting amid individual, structural and health system related barriers to ART adherence. Invigoration and maintenance of collectivist norms may however be necessary if its protective benefits are to be fully realized.
... In the developing world and the resourcelimited countries, there isn't too much evidence available on how this important aspect is handled (11), making it essential for HCPs to acquire insight into possible influencing factors in each patient before and during the ART treatment (20). In managing HIV/AIDS, retention to care is fundamental, from both clinical outcome and public health point of view, and in the absence of any "gold standards" for the adherence measurement (48), health-care policy makers must devise mechanism contextual to the local setting. ...
Background
It is widely accepted that for HIV-positive persons on highly active antiretroviral treatment, high levels of adherence to treatment regimens are essential for promoting viral suppression and preventing drug resistance.
Objectives
This qualitative study examines factors affecting the adherence to HIV/AIDS treatment among patients with HIV/AIDS at a local hospital in Malaysia.
Methods
The data from purposefully selected patients were collected by in-depth interviews using a pretested interview guide. Saturation was reached at the 13th interview. All interviews were audio-taped and transcribed verbatim for analysis using thematic content analysis.
Results
Fear and stigma of perceived negative image of HIV diagnosis, lack of disease understating, poor support from the community, and perceived severity or the treatment side effects were among the reasons of nonadherence. Appropriate education and motivation from the doctors and reduction in pill burden were suggested to improve adherence.
Conclusion
Educational interventions, self-management, and peer and community supports were among the factors suggested to improve adherence. This necessitates uncovering efficient ways to boost doctor–patient communication and recognizing the role of support group for the social and psychological well-being of the patients.
... There is growing concern however that in some settings, women's adherence to ART either during pregnancy and/or during the postpartum period may be suboptimal, and contribute in turn to increased risk of vertical HIV transmission. In addition, retaining individuals in ART services is a necessary precursor to treatment adherence [24]: individuals who do not attend ART appointments (and do not collect their medications) are not adherent to their medication [25]. ...
... Assim, o problema do VIH continua preocupante e não existe um conhecimento sistematizado sobre os fatores determinantes de adesão terapêutica nesta população em Nampula. [8][9][10] Confrontada com esta situação, a Faculdade de Ciências de Saúde (FCS) da Universidade Lúrio propôs-se realizar um trabalho de investigação operacional, destinado a avaliar a adesão à TARV na província de Nampula e propor e implementar atividades de promoção da adesão terapêutica. Este artigo apresenta o estudo da linha de base inicial e tem três objetivos: 1) Avaliar a adesão à TARV, [11][12] nos CSP na província de Nampula; 2) Identificar os fatores associados ao abandono da TARV na perceção dos pacientes; 3) Identificar os fatores associados ao abandono da TARV na perceção dos profissionais de saúde. ...
Objectives: To evaluate adherence to antiretroviral treatment in Nampula province and to identify the determinants of non-compliance. Study type: Observational study with quantitative and qualitative methods. Place: Five health centers in the Nampula province of Mozambique in 2014. Population: Patients infected with human immunodeficiency virus receiving antiretroviral treatment, patients who had abandoned treatment, and primary health care professionals. Methods: Patients on treatment and patients who were non-compliant with therapy completed a questionnaire, patient records (clinical files, pharmacy records, and statistical records) were reviewed, and interviews were conducted with health care professionals. Results: Abandonment of antiretroviral treatment reached 40%. We surveyed 208 patients on treatment and 86 patients who were non-compliant with therapy. Of these 70% were female and they were between 18 and 62 years of age. The main reason for non-compliance with treatment (36%) was stigma attached to having the infection. In addition 58% of patients do not have enough food and 37% suffer from depressive ideation. Good treatment adherence (>95% of pills were taken in the last three months) was found in 69% of patients, but 36 % of people who are adherent have a low CD4 count and 63% are not following the recommended treatment protocol. Conclusions: Perception of stigma from infection with the human immunodeficiency virus is considered the main reason for non-adherence with antiretroviral treatment, but food insecurity is also an important determinant. A treatment adherence rate of 69% explains the high incidence of opportunistic infections (27%). Abandonment of antiretroviral treatment in Nampula is a serious and complex problem due to individual, social and primary health care services factors. It will be necessary to develop an interdisciplinary intervention with patients, families, and health professionals, to reverse this situation and improve treatment adherence.
Blood biomarkers are an essential tool for healthcare providers to diagnose, monitor, and treat a wide range of medical conditions. Current reference values and recommended ranges often rely on population-level statistics, which may not adequately account for the influence of inter-individual variability driven by factors such as lifestyle and genetics. In this work, we introduce a novel framework for predicting future blood biomarker values and define personalized references through learned representations from lifestyle data (physical activity and sleep) and blood biomarkers. Our proposed method learns a similarity-based embedding space that captures the complex relationship between biomarkers and lifestyle factors. Using the UK Biobank (257K participants), our results show that our deep-learned embeddings outperform traditional and current state-of-the-art representation learning techniques in predicting clinical diagnosis. Using a subset of UK Biobank of 6440 participants who have follow-up visits, we validate that the inclusion of these embeddings and lifestyle factors directly in blood biomarker models improves the prediction of future lab values from a single lab visit. This personalized modeling approach provides a foundation for developing more accurate risk stratification tools and tailoring preventative care strategies. In clinical settings, this translates to the potential for earlier disease detection, more timely interventions, and ultimately, a shift towards personalized healthcare.
Blood tests are an essential tool for healthcare providers to diagnose, monitor, and treat a wide range of medical conditions. however, quantitative approaches for personalizing such metrics are nascent and often ignore important factors such as health behaviors. Moreover, recent studies have shown that raw (untransformed) representations of health records are inadequate for constructing predictive models, especially when considering a single time point. Here, we investigate the association of activity and sleep with blood biomarker ranges, and based on our results, propose Proteus, a new deep metric learning algorithm that accounts for health behaviors. We show that Proteus significantly improves the performance of several downstream analyses, including the prediction of future health risk in currently-healthy patients using a single laboratory visit. Building upon our findings, we additionally introduce DeepRange, a novel lifestyle-informed algorithm, which utilizes deep-learned embeddings for estimating personalized optimal blood test ranges. Our proposed methodology for personalized blood biomarker ranges and single-visit health risk prediction can be readily implemented and has the potential to significantly improve health outcomes by enabling early intervention and enhanced personalization.
Background
In 2014, UNAIDS set the target that 90% of individuals on antiretroviral therapy (ART) be virally suppressed. Here, we use data from the HPTN 071 (PopART) trial to report whether the introduction of universal testing and treatment has affected viral suppression or treatment adherence among individuals who self-reported they were taking ART, and identify risk factors for these outcomes.
Methods
This was a cross-sectional study nested within the randomly selected population cohort of the PopART trial. The trial took place in 21 communities in Zambia and South Africa. Analyses included 3570 HIV-positive participants who were seen at the second follow-up visit in 2016–17 and who self-reported that they were currently taking ART. Viral suppression was defined as HIV RNA of less than 400 copies per mL from a blood sample collected during the cohort visit, and ART adherence was measured using self-reporting (reported as no missed pills in last 7 days). Prevalences of these outcomes were compared across three trial arms using a two-stage approach suitable for clustered data. Each arm consisted of seven communities, with one arm receiving a combination HIV prevention package including immediate ART initiation, one receiving a combination HIV prevention package excluding immediate ART initiation and one arm receving standard of care. Risk factors for each of the outcomes were assessed using logistic regression.
Findings
Among the 3570 participants who self-reported that they were currently on ART, 416 (11·7%) of 3554 were not virally suppressed (16 were missing viral suppression status) and 345 (9·7%) of 3566 reported being non-adherent to ART (four were missing adherence status). The proportion not virally suppressed was higher in communities in South Africa (195 [16·4%] of 1191) than in Zambia (221 [9·4%] of 2363). There was no evidence that the prevalence of the outcomes differed between trial arms. There was evidence that men, younger individuals, individuals who reported participating in harmful alcohol use, and those who reported internalised stigma were more likely to be non-adherent, and not virally suppressed.
Interpretation
The results assuaged concerns that early ART initiation in a universal testing and treatment setting could lead to reduced adherence and viral suppression.
Funding
US National Institute of Allergy and Infectious Diseases (which is a part of the National Institutes of Health), the International Initiative for Impact Evaluation with support from the Bill & Melinda Gates Foundation, US President's Emergency Plan for AIDS Relief, and Medical Research Council UK.
Adolescents living with HIV (ALHIV) struggle to remain engaged in HIV-related care and adhere to antiretroviral treatment (ART) due to a myriad of physical, psychological and cognitive-developmental challenges. We report on the profile of ALHIV aged 10-19 years on ART and the clinical factors associated with their retention in care. A retrospective cohort analysis was conducted with 16,108 ALHIV, aged 10-19 years, who were enrolled in 136 ART clinics in the Ehlanzeni district. Anonymised data were obtained from electronic medical records (Tier.net). Trends in retention in care among adolescents on ART was described using Kaplan-Meier survival estimates. Cox proportional analysis was performed to identify factors associated with retention in care over 2 years. More than half (53%) were females, and median duration on ART was 8 months. Retention in care among adolescents at months 6, 12, 18 and 24 was 90.5%, 85.4%, 80.8% and 76.2%, respectively. After controlling for confounders, risk of dying or lost to follow up increased for female adolescents (aHR = 1.28, 95% CI 1.10-1.49); being initiated on ART while pregnant (aHR = 2.72, 95% CI 1.99-3.69); history of TB infection (aHR = 1.71, 95% CI 1.10-2.65); and started ART at age 10-14 years (aHR = 2.45, 95% CI 1.96-3.05), and 15-19 years (aHR = 9.67, 95% CI 7.25-12.89). Retention in care among adolescents on ART over two-year period was considerably lower than the UNAIDS 2030 target of 95%. Of particular concern for intervention is the lower rates of retention in care among females and pregnant adolescents and starting ART between the ages of 10 and 19 years. Family or caregivers and peer support groups centred interventions designed to promote early initiation and retention in care through early case identification are needed.
Adolescents living with HIV (ALHIV) face unique developmental challenges that increase the risk of unsuppressed viral loads. Current reviews present a need for proven interventions to improve viral suppression among ALHIV on ART, who have a history of unsuppressed viral loads. This systematic review aims to synthesize and appraise evidence of the effectiveness of interventions to improve treatment outcomes among ALHIV with unsuppressed viral loads. Six bibliographic databases were searched for published studies and gray literature from 2010 to 2021. The risk of bias and certainty of evidence was assessed using the ROBINS-I tool, CASP checklists and GRADE. A total of 28 studies were eligible for full-text screening; and only three were included in the qualitative synthesis. In addition, two studies were included from website searches. Four types of interventions to improve viral suppression were identified, namely: intensive adherence counselling; community- and facility-based peer-led differentiated service delivery (DSD); family based economic empowerment; and conditional economic incentives and motivational interviewing. We strongly recommend peer-led community-based DSD interventions, intensive adherence counselling, and family-based economic empowerment as potential interventions to improve viral suppression among ALHIV.
With the introduction of antiretroviral therapy (ART), many HIV-infected children are growing into adolescence and adulthood. A facility-based cross-sectional study was conducted at the Fevers Unit of one of the teaching hospitals in Ghana. The Morisky Medication Adherence Scale (MMAS-8) and pill count were used to assess adherence, while measured viral load levels of participants were used to assess viral suppression. The rate of viral suppression (<400 copies/ml) was 68.2%. Participants with high MMAS-8 scores were 8.4 times more likely to be virally suppressed compared to those with low MMAS-8 scores (OR = 8.4, p = 0.003, 95% CI: 2.11–33.48). The commonest reason for missing doses of their antiretroviral drugs (ARVs) was forgetfulness. Efforts must be made by all stakeholders involved in HIV care to engage adolescents and young adults living with HIV (AYALHIV) on personal and/or group levels to help identify and improve particular ART adherence issues so as to increase viral suppression rates.
Background: Non-adherence to anti-retroviral therapy (ART) is responsible for up to 75% of the unsuppressed viral load among people living with HIV (PLWH) on ART. Intensive adherence counseling (IAC) is an intervention recommended by the World Health Organization to improve adherence. In 2016, the Ugandan Ministry of Health introduced IAC to improve viral load suppression. This study evaluated the effect and experiences of providing IAC in an urban HIV care center in Kampala, Uganda.
Methods: This was a sequential explanatory mixed-method study that compared viral load suppression in the period with IAC intervention to a period without IAC at Kisenyi Health centre IV. Data were abstracted from patient files. The effect on viral load suppression of IAC and associated factors was analyzed using modified Poisson regression with robust standard errors. Using in-depth interviews and an inductive analysis approach in Atlas. ti, we also explored experiences of providing IAC among healthcare workers.
Results: A total of 500 records were sampled: 249(49.8%) in the intervention period and 251(51.2%) in the pre-intervention period. The mean age of clients was 34.8 years (SD±12.8), and 326/500 (65.2%) were females. Majority were on a Lopinavir/ritonavir based regimen [314 (62.8%)], and the median duration on ART was 30.8 months (IQR: 12.5–51.7). Over the intervention period, all eligible clients received IAC [249/249 (100.0%)]. Of those, 143 (44.1%) achieved viral load suppression compared to 46 (26.3%) in the pre-intervention period. Receiving IAC significantly increased viral load suppression by 22% (aPR = 1.22, 95% CI: 1.01–1.47). Participants on Lopinavir/ritonavir-based regimen were less likely to suppress (aPR= 0.11, 95%CI: 0.08–0.15) than those on Efavirenz or Nevirapine based regimens. All the interviewed healthcare workers lauded IAC for improving ART adherence. However, non-disclosure, social-economic constraints, lack of a multidisciplinary team and work overload hindered adherence during IAC.
Conclusions: The full potential of IAC in achieving viral suppression in this setting has not been reached, probably due to a combination of the health care system and patient-related factors. Provision of adequate IAC necessities and use of patient centered approach during IAC should be emphasized to obtain the maximum benefit of IAC.
Background: Mental health disorders such as high levels of anxiety, isolation, depression and suicide ideation reported among young people living with HIV (10-24; YPLWH) contribute significantly to poor medication adherence and retention in care. While there is evidence supporting the role of psychosocial support interventions in promoting adherence and retention in antiretroviral treatment (ART) among adults living with HIV, there is little evidence on the role of psychosocial support on medication adherence among YPLWH . This scoping review was designed to identify and classify the types and effects of psychosocial support interventions designed to improve adherence and retention in ART among adolescents and young people living with HIV globally.
Method: We searched six electronic databases (i.e., Scopus, Pubmed and EBSCOHost (Academic Search Premier, CINAHL, Psycarticles and Medline). Six relevant articles published between 2011 and 2019 met our inclusion criteria. We extracted information relevant to the nature and outcomes of the reported interventions using thematic content analysis informed by the Population, Intervention, comparison, outcome, and time (PICOT) framework.
Results: Four distinctive treatment modalities that focused on improving ART adherence and retention in care were identified: individual counselling, support groups, family-centered services, and treatment supporters.
Conclusion: There is a dearth of psychosocial support interventions to improve adherence and retention in ART amongst adolescents and young adults living with HIV. Future research and programming should seek to address psychosocial support interventions or approaches specifically designed to address the needs of adolescents and young adults living with HIV.
PROSPERO: Registration CRD42018105057
Background: Mental health disorders such as high levels of anxiety, isolation, depression and suicide reported among adolescents and young people living with HIV contribute significantly to poor medication adherence and retention in care. While there is evidence supporting the role of psychosocial support interventions in promoting adherence and retention in antiretroviral treatment (ART) among adults living with HIV, there is little evidence on the role of psychosocial support on medication adherence among adolescents living with HIV. This scoping review was designed to identify and classify the types and effects of psychosocial support interventions designed to improve adherence and retention in ART among adolescents and young people living with HIV globally.
Method: We searched six electronic databases (i.e., Scopus, Pubmed and EBSCOHost (Academic Search Premier, CINAHL, Psycarticles and Medline). Six relevant articles published between 2011 and 2019 met our inclusion criteria. We extracted information relevant to the nature and outcomes of the reported interventions using thematic content analysis informed by the Population, Intervention, comparison, outcome, and time (PICOT) framework.
Results: Four distinctive treatment modalities that focused on improving ART adherence and retention in care were identified: individual counselling, support groups, family-centered services, and treatment supporters.
Conclusion: There is a dearth of psychosocial support interventions to improve adherence and retention in ART amongst adolescents and young adults living with HIV. Future research and programming should seek to address psychosocial support interventions or approaches specifically designed to address the needs of adolescents and young adults living with HIV.
Directly observed therapy (DOT) for antiretroviral therapy (ART) may improve adherence, but there are limited data on its clinical effectiveness.
Adult patients initiating ART in a public clinic in Cape Town, South Africa, were randomized to treatment-supporter DOT-ART or self-administered ART. DOT-ART patients and supporters received baseline and follow-up training and monitoring. The primary endpoints were the proportions of patients with HIV viral load less than 400 copies/ml and change in CD4 cell counts at 12 and 24 months.
Two hundred and seventy-four patients enrolled (137 in each arm) and baseline characteristics were similar for both arms. The study was stopped early for futility by an independent Data and Safety Monitoring Board. In an intention-to-treat analysis, the proportions of patients with viral load less than 400 copies/ml at 12 months were 72.8% in the DOT-ART arm and 68.4% in the Self-ART arm (P = 0.42). DOT-ART patients had greater median CD4 cell count (cells/microl) increases at 6 months [148 (IQR 84-222) vs. 111 (IQR 44-196) P = 0.02] but similar results at all other time-points. Survival was significantly better in the DOT-ART arm (9 deaths, 6.6%) than in the Self-ART arm (20 deaths, 14.6%; log-rank P = 0.02). In Cox regression analysis, mortality was independently associated with study arm [DOT vs. self-ART; HR 0.38, 95% confidence interval (CI) 0.17-0.86].
DOT-ART showed no effect on virologic outcomes but was associated with greater CD4 cell count increases at 6-month follow-up. Survival was significantly better for DOT-ART compared to Self-ART, but this was not explained by improved virologic or immunologic outcomes.
The objectives are to compare the effectiveness of cell phone-supported SMS messaging to standard care on adherence, quality of life, retention, and mortality in a population receiving antiretroviral therapy (ART) in Nairobi, Kenya.
A multi-site randomized controlled open-label trial. A central randomization centre provided opaque envelopes to allocate treatments. Patients initiating ART at three comprehensive care clinics in Kenya will be randomized to receive either a structured weekly SMS ('short message system' or text message) slogan (the intervention) or current standard of care support mechanisms alone (the control). Our hypothesis is that using a structured mobile phone protocol to keep in touch with patients will improve adherence to ART and other patient outcomes. Participants are evaluated at baseline, and then at six and twelve months after initiating ART. The care providers keep a weekly study log of all phone based communications with study participants. Primary outcomes are self-reported adherence to ART and suppression of HIV viral load at twelve months scheduled follow-up. Secondary outcomes are improvements in health, quality of life, social and economic factors, and retention on ART. Primary analysis is by 'intention-to-treat'. Sensitivity analysis will be used to assess per-protocol effects. Analysis of covariates will be undertaken to determine factors that contribute or deter from expected and determined outcomes.
This study protocol tests whether a novel structured mobile phone intervention can positively contribute to ART management in a resource-limited setting.
In many HIV programmes in Africa, patients are assessed clinically and prepared for antiretroviral treatment over a period of 4-12 weeks. Mortality rates following initiation of ART are very high largely because patients present late with advanced disease. The rates of mortality and retention during the pre-treatment period are not well understood. We conducted an observational study to determine these rates.
HIV-infected subjects presenting at The AIDS Support Clinic in Jinja, SE Uganda, were assessed for antiretroviral therapy (ART). Eligible subjects were given information and counselling in 3 visits done over 4-6 weeks in preparation for treatment. Those who did not complete screening were followed-up at home. Survival analysis was done using poisson regression.
4321 HIV-infected subjects were screened of whom 2483 were eligible for ART on clinical or immunological grounds. Of these, 637 (26%) did not complete screening and did not start ART. Male sex and low CD4 count were associated independently with not completing screening. At follow-up at a median 351 days, 181 (28%) had died, 189 (30%) reported that they were on ART with a different provider, 158 (25%) were alive but said they were not on ART and 109 (17%) were lost to follow-up. Death rates (95% CI) per 100 person-years were 34 (22, 55) (n.18) within one month and 37 (29, 48) (n.33) within 3 months. 70/158 (44%) subjects seen at follow-up said they had not started ART because they could not afford transport.
About a quarter of subjects eligible for ART did not complete screening and pre-treatment mortality was very high even though patients in this setting were well informed. For many families, the high cost of transport is a major barrier preventing access to ART.
Success of antiretroviral therapy depends on high rates of adherence, but few interventions are effective. Our objective was to determine if modified directly observed therapy (mDOT) improves initial antiretroviral success.
In an open-label, randomized trial comparing mDOT (Monday-Friday for 24 weeks) and self-administered therapy with lopinavir/ritonavir soft gel capsules (800 mg/200 mg), emtricitabine (200 mg), and either extended-release stavudine (100 mg) or tenofovir (300 mg), all taken once daily, 82 participants received mDOT and 161, self-administered therapy. Participant eligibility included a plasma human immunodeficiency virus RNA level higher than 2000 copies/mL and being naïve to antiretroviral therapy. A total of 243 participants were predominantly male (79%) (median age, 38 years), with 84 Latinos (35%), 74 non-Latino blacks (30%), and 79 non-Latino whites (33%). The study was conducted at 23 AIDS Clinical Trials Group (ACTG) sites in the United States and 1 site in South Africa between October 2002 and January 2006. The primary outcome was virologic success at week 24 and secondary outcomes were virologic success, clinical progression, and adherence at week 48.
Over 24 weeks, mDOT had greater virologic success (0.91; 95% confidence interval [CI], 0.81 to 0.95) than self-administered therapy (0.84; 95% CI, 0.77 to 0.89), but the difference (0.07; lower bound 95% CI, -0.01) did not reach the prespecified threshold of 0.075. Over 48 weeks, virologic success was not significantly different between mDOT (0.72; 95% CI, 0.61 to 0.81) and self-administered therapy (0.78; 95% CI, 0.70 to 0.84) (difference, -0.06; 95% CI, -0.18 to 0.07 [P = .19]).
The potential benefit of mDOT was marginal and not sustained after discontinuation. Modified DOT should not be incorporated routinely for care of treatment-naïve human immunodeficiency virus type 1-infected patients.
We conducted a study to assess the effect of family-based treatment on adherence amongst HIV-infected parents and their HIV-infected children attending the Mother-To-Child-Transmission Plus program in Kampala, Uganda. Adherence was assessed using home-based pill counts and self-report. Mean adherence was over 94%. Depression was associated with incomplete adherence on multivariable analysis. Adherence declined over time. Qualitative interviews revealed lack of transportation money, stigma, clinical response to therapy, drug packaging, and cost of therapy may impact adherence. Our results indicate that providing ART to all eligible HIV-infected members in a household is associated with excellent adherence in both parents and children. Adherence to ART among new parents declines over time, even when patients receive treatment at no cost. Depression should be addressed as a potential barrier to adherence. Further study is necessary to assess the long-term impact of this family treatment model on adherence to ART in resource-limited settings.
To measure the clinical and immunological outcomes of HIV positive adult patients receiving combination antiretroviral therapy in conflict affected northern Uganda.
Prospective cohort study.
Gulu District, northern Uganda.
1625 adults (aged over 14 years) receiving combination antiretroviral therapy.
Primary outcome: all cause mortality. Secondary outcomes: impact of covariates (sex, age, CD4 count at start, adherence, tuberculosis at start, duration of treatment, and internally displaced person status) on mortality.
Sixty nine (4.2%) patients died during follow-up. The mortality incidence rate was 3.48 (95% confidence interval 2.66 to 4.31) per 100 person years. Patients started treatment with a median CD4 count of 157 (interquartile range 90-220) cells/mul; most (1009; 63%) had World Health Organization stage 2 defined illness. Sixty two patients had pulmonary tuberculosis at the start of treatment. Of the 1521 patients with adherence data, 118 (7.8%) had adherence of less than 95% and 1403 (92.2%) had adherence of 95% or above.
Patients receiving combination antiretroviral therapy in conflict affected northern Uganda had a mortality comparable to that of patients in peaceful, low income settings and better adherence than patients in higher income settings. These favourable findings highlight the need to expand access to combination antiretroviral therapy in populations affected by armed conflict.
Individuals living with HIV/AIDS in sub-Saharan Africa generally take more than 90% of prescribed doses of antiretroviral therapy (ART). This number exceeds the levels of adherence observed in North America and dispels early scale-up concerns that adherence would be inadequate in settings of extreme poverty. This paper offers an explanation and theoretical model of ART adherence success based on the results of an ethnographic study in three sub-Saharan African countries.
Determinants of ART adherence for HIV-infected persons in sub-Saharan Africa were examined with ethnographic research methods. 414 in-person interviews were carried out with 252 persons taking ART, their treatment partners, and health care professionals at HIV treatment sites in Jos, Nigeria; Dar es Salaam, Tanzania; and Mbarara, Uganda. 136 field observations of clinic activities were also conducted. Data were examined using category construction and interpretive approaches to analysis. Findings indicate that individuals taking ART routinely overcome economic obstacles to ART adherence through a number of deliberate strategies aimed at prioritizing adherence: borrowing and "begging" transport funds, making "impossible choices" to allocate resources in favor of treatment, and "doing without." Prioritization of adherence is accomplished through resources and help made available by treatment partners, other family members and friends, and health care providers. Helpers expect adherence and make their expectations known, creating a responsibility on the part of patients to adhere. Patients adhere to promote good will on the part of helpers, thereby ensuring help will be available when future needs arise.
Adherence success in sub-Saharan Africa can be explained as a means of fulfilling social responsibilities and thus preserving social capital in essential relationships.
Abstract Background Antiretroviral therapy (ART) dramatically improves outcomes for children in Africa; however excellent adherence is required for treatment success. This study describes the utility of different measures of adherence in detecting lapses in infants and young children in Cape Town, South Africa. Methods In a prospective cohort of 122 HIV-infected children commenced on ART, adherence was measured monthly during the first year of treatment by medication return (MR) for both syrups and tablets/capsules. A questionnaire was administered to caregivers after 3 months of treatment to assess experience with giving medication and self-reported adherence. Viral and immune response to treatment were assessed at the end of one year and associations with measured adherence determined. Results Medication was returned for 115/122 (94%) children with median age (IQR) of 37 (16 – 61) months. Ninety-one (79%) children achieved annual average MR adherence ≥ 90%. This was an important covariate associated with viral suppression after adjustment for disease severity (OR = 5.5 [95%CI: 0.8–35.6], p = 0.075), however was not associated with immunological response to ART. By 3 months on ART, 13 (10%) children had deceased and 11 (10%) were lost to follow-up. Questionnaires were completed by 87/98 (90%) of caregivers of those who remained in care. Sensitivity of poor reported adherence (missing ≥ 1 dose in the previous 3 days) for MR adherence
To analyse the early loss of patients to antiretroviral therapy (ART) programmes in resource-limited settings.
Using data on 5491 adult patients starting ART (median age 35 years, 46% female) in 15 treatment programmes in Africa, Asia and South America with (3) 12 months of follow-up, we investigated risk factors for no follow-up after treatment initiation, and loss to follow-up or death in the first 6 months.
Overall, 211 patients (3.8%) had no follow-up, 880 (16.0%) were lost to follow-up and 141 (2.6%) were known to have died in the first 6 months. The probability of no follow-up was higher in 2003-2004 than in 2000 or earlier (odds ratio, OR: 5.06; 95% confidence interval, CI: 1.28-20.0), as was loss to follow-up (hazard ratio, HR: 7.62; 95% CI: 4.55-12.8) but not recorded death (HR: 1.02; 95% CI: 0.44-2.36). Compared with a baseline CD4-cell count (3) 50 cells/microl, a count < 25 cells/microl was associated with a higher probability of no follow-up (OR: 2.49; 95% CI: 1.43-4.33), loss to follow-up (HR: 1.48; 95% CI: 1.23-1.77) and death (HR: 3.34; 95% CI: 2.10-5.30). Compared to free treatment, fee-for-service programmes were associated with a higher probability of no follow-up (OR: 3.71; 95% CI: 0.97-16.05) and higher mortality (HR: 4.64; 95% CI: 1.11-19.41).
Early patient losses were increasingly common when programmes were scaled up and were associated with a fee for service and advanced immunodeficiency at baseline. Measures to maximize ART programme retention are required in resource-poor countries.
Combination antiretroviral therapy with protease inhibitors has transformed HIV infection from a terminal condition into one that is manageable. However, the complexity of regimens makes adherence to therapy difficult.
To assess the effects of different levels of adherence to therapy on virologic, immunologic, and clinical outcome; to determine modifiable conditions associated with suboptimal adherence; and to determine how well clinicians predict patient adherence.
Prospective, observational study.
HIV clinics in a Veterans Affairs medical center and a university medical center.
99 HIV-infected patients who were prescribed a protease inhibitor and who neither used a medication organizer nor received their medications in an observed setting (such as a jail or nursing home).
Adherence was measured by using a microelectronic monitoring system. The adherence rate was calculated as the number of doses taken divided by the number prescribed. Patients were followed for a median of 6 months (range, 3 to 15 months).
During the study period, 45,397 doses of protease inhibitor were monitored in 81 evaluable patients. Adherence was significantly associated with successful virologic outcome (P < 0.001) and increase in CD4 lymphocyte count (P = 0.006). Virologic failure was documented in 22% of patients with adherence of 95% or greater, 61% of those with 80% to 94.9% adherence, and 80% of those with less than 80% adherence. Patients with adherence of 95% or greater had fewer days in the hospital (2.6 days per 1000 days of follow-up) than those with less than 95% adherence (12.9 days per 1000 days of follow-up; P = 0.001). No opportunistic infections or deaths occurred in patients with 95% or greater adherence. Active psychiatric illness was an independent risk factor for adherence less than 95% (P = 0.04). Physicians predicted adherence incorrectly for 41% of patients, and clinic nurses predicted it incorrectly for 30% of patients.
Adherence to protease inhibitor therapy of 95% or greater optimized virologic outcome for patients with HIV infection. Diagnosis and treatment of psychiatric illness should be further investigated as a means to improve adherence to therapy.
In sub-Saharan Africa, tuberculosis (TB) has increased over the last two decades due to the human immunodeficiency virus pandemic. In Malawi, 20630 new TB patients were notified to the National Tuberculosis Programme in 1996, a fourfold increase since 1986. Due to this increase in cases and lack of resources (both human and monetary) it is becoming more difficult to ensure directly observed treatment (DOT) in the TB wards.
In Ntcheu district, Malawi, a new TB regimen was introduced from April 1996 in which patients received supervised treatment by either a health worker or a guardian (i.e., family member). Adherence to the different treatment options was measured by form checks, tablet counts, and tests for detecting isoniazid in the urine. Adherence was measured at 2, 4 and 8 weeks after onset of TB treatment.
Overall adherence rate was 95-96%. Inpatients showed the highest adherence rates. Patients on guardian-based DOT (GB-DOT) (n = 35) showed 94% adherence, while patients on health centre based DOT (n = 40) showed more non-adherent behaviour: 11% according to monitoring forms, 14% according to tablet counts and 16% according to urine tests.
The results suggest that decentralised care is a feasible option for anti-tuberculosis treatment and that guardians can supervise TB treatment just as well as health workers during the intensive phase of TB treatment.
In 2000, acquired immunodeficiency syndrome (AIDS) overtook tuberculosis (TB) as the world's leading infectious cause of adult deaths. In affluent countries, however, AIDS mortality has dropped sharply, largely because of the use of highly active antiretroviral therapy (HAART). Antiretroviral agents are not yet considered essential medications by international public health experts and are not widely used in the poor countries where human immunodeficiency virus (HIV) takes its greatest toll. Arguments against the use of HAART have mainly been based on the high cost of medications and the lack of the infrastructure necessary for using them wisely. We re- examine these arguments in the setting of rising AIDS mortality in developing countries and falling drug prices, and describe a small community-based treatment programme based on lessons gained in TB control. With the collaboration of Haitian community health workers experienced in the delivery of home-based and directly observed treatment for TB, an AIDS-prevention project was expanded to deliver HAART to a subset of HIV patients deemed most likely to benefit. The inclusion criteria and preliminary results are presented. We conclude that directly observed therapy (DOT) with HAART, "DOT-HAART", can be delivered effectively in poor settings if there is an uninterrupted supply of high-quality drugs.
The objective of this study was to systematically characterize the incidence and determinants of antiretroviral resistance in the HOMER (Highly Active Antiretroviral Therapy [HAART] Observational Medical Evaluation and Research) cohort of 1191 human immunodeficiency virus-infected, antiretroviral-naive adults initiating HAART in British Columbia, Canada.
All plasma samples with plasma virus loads (pVLs) >1000 copies/mL collected during the first 30 months of follow-up were genotyped for drug resistance. The primary outcome measure was time to the first detection of major drug-resistance mutation(s). Cox proportional hazard regression was used to identify factors significantly associated with the detection of drug-resistance mutations.
Drug-resistance mutations were detected in 298 subjects (25%). Factors significantly associated with detection of drug-resistance mutations included high baseline pVL (multivariate hazard ratio [HR], 1.59; P<.001) and adherence (estimated using prescription-refill data and/or untimed plasma drug-concentration measurements). When compared with subjects with low (0%-<20%) prescription-refill percentages, subjects at an elevated risk of harboring drug-resistance mutations were those with relatively high but imperfect prescription-refill percentages (80%-<90%; multivariate HR, 4.15; P<.001) and those with essentially perfect (>/=95%) refill percentages but with 2 plasma drug concentrations below the steady-state trough concentration minus 1 standard deviation (multivariate HR, 4.57; P<.001). Initial use of nonnucleoside reverse-transcriptase inhibitor-based HAART was significantly associated with multiclass drug resistance (multivariate HR, 1.84; P=.001).
High baseline pVLs and substantial but imperfect levels of adherence were major predictors of antiretroviral resistance.
Background
The introduction of combination antiretroviral therapy and protease inhibitors has led to reports of falling mortality rates among people infected with HIV-1. We examined the change in these mortality rates of HIV-1-infected patients across Europe during 1994-98, and assessed the extent to which changes can be explained by the use of new therapeutic regimens.
Methods
We analysed data from EuroSIDA, which is a prospective, observational, European, multicentre cohort of 4270 HIV-1-infected patients. We compared death rates in each 6 month period from September, 1994, to March, 1998.
Findings
By March, 1998, 1215 patients had died. The mortality rate from March to September, 1995, was 23·3 deaths per 100 person-years of follow-up (95% Cl 20·6–26·0), and fell to 4·1 per 100 person-years of follow-up (2·3–5·9) between September, 1997, and March, 1998. From March to September, 1997, the death rate was 65·4 per 100 person-years of follow-up for those on no treatment, 7·5 per 100 person-years of follow-up for patients on dual therapy, and 3·4 per 100 person-years of follow-up for patients on triple-combination therapy. Compared with patients who were followed up from September, 1994, to March, 1995, patients seen between September, 1997, and March, 1998, had a relative hazard of death of 0·16 (0·08–0·32), which rose to 0·90 (0·50–1·64) after adjustment for treatment.
Interpretation
Death rates across Europe among patients infected with HIV-1 have been falling since September, 1995, and at the begining of 1998 were less than a fifth of their previous level. A large proportion of the reduction in mortality could be explained by new treatments or combinations of treatments.
OBJECTIVES To evaluate a 5-year HIV care programme (2003-2007) in the Sihanouk Hospital Center of HOPE, Phnom Penh, Cambodia.
METHODS Analysis of routine programme indicators per year: number of new patients, active patients, antiretroviral therapy (ART) coverage in the cohort, mortality and loss to follow-up. Comparison of mortality before and after the start of ART using Kaplan-Meier survival curves. Analysis of risk factors using Cox regression for the combined endpoint of mortality and loss to follow-up in patients on ART.
RESULTS 3844 patients were registered in the hospital between March 2003 and December 2007. The mortality and loss to follow-up rate fell and paralleled the rise of ART coverage from 23% in 2003 to 90% in 2007. The mortality and the loss to follow-up rate was significantly higher in patients not on ART but eligible (Log rank P < 0.001). The combined endpoint of mortality and loss to follow-up was 48.7% after one year in patients who were waiting for ART. 1667 patients were started on ART. The combined endpoint (mortality and loss to follow-up) in this group was 11.5% at 12 months and 14.2% at 24 months. Risk factors for mortality in the ART group were male sex, CD4 count <50 cells/microl, BMI <18 and haemoglobin levels <10 g/dl.
CONCLUSION Better access to ART is associated with lower mortality and fewer losses to follow-up. Pre-ART attrition remains significant. Strategies are needed to enable an earlier start of ART and to promote retention in care.
To determine short- and long-term efficacy of modified directly observed therapy (m-DOT) on antiretroviral adherence.
Randomized controlled trial. SETTING AND ANALYTIC APPROACH: From September 2003 to November 2004, 234 HIV-infected adults were assigned m-DOT (24 weeks of twice weekly health center visits for nurse-observed pill ingestion, adherence support, and medication collection) or standard care. Follow-up continued until week 72. Self-reported and pill-count adherence and, secondarily, viral suppression and body mass index measures are reported. Generalized estimating equations adjusted for intraclient clustering and covariates were used.
During weeks 1-24, 9.1% (9/99) of m-DOT participants reported missing doses compared with 19.1% (20/105) of controls (P = 0.04) and 96.5% (517/571) of m-DOT pill-count measures were >or=95% compared with 86.1% (445/517) in controls [adjusted odds ratio = 4.4; 95% confidence interval (CI) = 2.6 to 7.5; P < 0.001. Adherence with m-DOT was 4.8 times greater (95% CI = 2.7 to 8.6; P < 0.001) with adjustment for depression and HIV-related hospitalization. In weeks 25-48, adherence with m-DOT (488/589) was similar to controls (507/630). Viral suppression at 48 weeks was 2.0 times (95% CI = 0.8 to 5.2; P = 0.13) as likely in m-DOT participants as controls. M-DOT patients had larger body mass index increases at 24 weeks (2.2 vs 1.4 kg/m3; P = 0.014). Viral suppression was more likely at week 48 (21/25 vs 13/22; P = 0.057) and week 72 (27/30 vs 15/23; P = 0.027) among depressed participants receiving m-DOT.
M-DOT increased adherence, most notably among depressed participants.
National surveillance data show recent, marked reductions in morbidity and mortality associated with the acquired immunodeficiency syndrome (AIDS). To evaluate these declines, we analyzed data on 1255 patients, each of whom had at least one CD4+ count below 100 cells per cubic millimeter, who were seen at nine clinics specializing in the treatment of human immunodeficiency virus (HIV) infection in eight U.S. cities from January 1994 through June 1997.
Mortality among the patients declined from 29.4 per 100 person-years in the first quarter of 1995 to 8.8 per 100 in the second quarter of 1997. There were reductions in mortality regardless of sex, race, age, and risk factors for transmission of HIV. The incidence of any of three major opportunistic infections (Pneumocystis carinii pneumonia, Mycobacterium avium complex disease, and cytomegalovirus retinitis) declined from 21.9 per 100 person-years in 1994 to 3.7 per 100 person-years by mid-1997. In a failure-rate model, increases in the intensity of antiretroviral therapy (classified as none, monotherapy, combination therapy without a protease inhibitor, and combination therapy with a protease inhibitor) were associated with stepwise reductions in morbidity and mortality. Combination antiretroviral therapy was associated with the most benefit; the inclusion of protease inhibitors in such regimens conferred additional benefit. Patients with private insurance were more often prescribed protease inhibitors and had lower mortality rates than those insured by Medicare or Medicaid.
The recent declines in morbidity and mortality due to AIDS are attributable to the use of more intensive antiretroviral therapies.
Antiretroviral therapy (ART) is an effective strategy for preventing disease progression of HIV infection, particularly when patients adhere closely to the treatment regimen. However, ART medications can cause side effects, including metabolic complications that can impact patients' adherence levels. Selected chronic complications associated with ART include lipodystrophy, hyperlipidemia, insulin resistance and diabetes, peripheral neuropathy, and bone disorders such as osteopenia/osteoporosis. In this article, we review the effects of these metabolic complications on ART adherence and approaches to prevent or reverse them.
To examine the loss to care and mortality rates before starting antiretroviral therapy (ART) among ART eligible HIV-infected patients in Durban, South Africa. Design: Retrospective cohort study.
We reviewed data from ART eligible adults (> or = 18 years) at an urban HIV clinic that charges a monthly fee from July to December 2006. ART eligibility was based on CD4 count < or = 200 cells per microliter or clinical criteria and a psychosocial assessment. Patients who did not start ART and were lost within 3 months were phoned. Correlates of loss to care were evaluated using logistic regression.
During the study period, 501 patients registered for ART training. Mean time from initial CD4 count to first ART training was 3.6 months (interquartile range 2.3-3.9 months). Four hundred eight patients (81.4%) were in care and on ART at 3-month follow-up, and 11 (2.2%) were in care but had not initiated ART. Eighty-two ART eligible patients (16.4%) were lost before ART initiation. Of these, 28 (34.1%) had died; two thirds of deaths occurred before or within 2 months after the first ART training. Despite multiple attempts, 32 patients (39%) were unreachable by phone. Lower baseline CD4 counts (< or = 100 cells/microL) and unemployment were independently associated with being lost.
Loss to care and death occur frequently before starting ART at an HIV clinic in Durban, South Africa. This delay from CD4 count to ART training, even among those with the lowest CD4 counts, highlights the need for interventions that improve linkage to care and prioritize ART initiation for those with low baseline CD4 counts.
Tuberculosis (TB) is the leading cause of death among HIV-infected patients worldwide. In KwaZulu-Natal, South Africa, 80% of TB patients are HIV coinfected, with high treatment default and mortality rates. Integrating TB and HIV care may be an effective strategy for improving outcomes for both diseases.
Prospective operational research study treating TB/HIV-coinfected patients in rural KwaZulu-Natal with once-daily antiretroviral (ARV) therapy concurrently with TB therapy by home-based, modified directly observed therapy. Patients were followed for 12 months after ARV initiation.
Of 119 TB/HIV-coinfected patients enrolled, 67 (56%) were female, mean age was 34.0 years, and median CD4 count was 78.5 cells per cubic millimeter. After 12 months on ARVs, mean CD4 count increase was 211 cells per cubic millimeter, and 88% had an undetectable viral load; 84% completed TB treatment. Thirteen patients (11%) died; 10 (77%) with multidrug-resistant or extensively drug-resistant TB. There were few severe adverse events or immune reconstitution events. Adherence was high with 93% of study visits attended and 99% of ARV doses taken.
Integration of TB and HIV treatment in a rural setting using concurrent home-based therapy resulted in excellent adherence and TB and HIV outcomes. This model may result in successful management of both diseases in other rural resource-poor settings.
Numerous national antiretroviral (ARV) treatment initiatives offering protease inhibitor-sparing combination antiretroviral therapy (cART) have recently commenced in southern Africa, the first of which began in Botswana in January 2002. Evaluation of the efficacy and tolerability of various protease inhibitor-sparing cART regimens requires intensive study in the region, as does investigation of the development of drug resistance and the optimal means of sustaining adherence. The "Tshepo" Study is the first large-scale, randomized, clinical trial that addresses these important issues among HIV-1 subtype C-infected ARV treatment-naive adults in southern Africa.
The Tshepo Study is a completed, open-labeled, randomized study that enrolled 650 ARV-naive adults between December 2002 and 2004. The study is a 3 x 2 x 2 factorial design comparing the efficacy and tolerability among factors: (1) 3 combinations of nucleoside reverse transcriptase inhibitors (NRTIs): zidovudine (ZDV) + lamivudine (3TC), ZDV + didanosine (ddI), and stavudine (d4T) + 3TC; (2) 2 different nonnucleoside reverse transcriptase inhibitors (NNRTIs): nevirapine and efavirenz; and (3) 2 different adherence strategies: the current national "standard of care" versus an "intensified adherence strategy" incorporating a "community-based directly observed therapy." Study patients were stratified into 2 balanced CD4 T-cell count groups: less than 201 versus 201-350 cells per cubic millimeter with viral load greater than 55,000 copies per milliliter. Following Data Safety Monitoring Board recommendations in April 2006, ZDV/ddI-containing arms were discontinued due to inferiority in primary end point, namely, virologic failure with resistance. We report both overall data and pooled data from patients receiving ZDV/ddI- versus ZDV/3TC- and d4T/3TC-containing cART through April 1, 2006.
Four hundred fifty-one females (69.4%) and 199 males with a median age of 33.3 years were enrolled into the study. The median follow-up as of April 1, 2006, was 104 weeks, and loss to follow-up rate at 2 years was 4.1%. The median baseline CD4 T-cell count was 199 cells per cubic millimeter [interquartile ratio (IQR) 136-252], and the median plasma HIV-1 RNA level was 193,500 copies per milliliter (IQR 69-250, 472-500). The proportion of participants with virologic failure and genotypic resistance mutations was 11% in those receiving ZDV/ddI-based cART versus 2% in those receiving either ZDV/3TC- or d4T/3TC-based cART (P = 0.002). The median CD4 T-cell count increase at 1 year was 137 cells per cubic millimeter (IQR 74-223) and 199 cells per cubic millimeter (IQR 112-322) at 2 years with significantly lower gain in the ZDV/ddI arm. At 1 and 2 years, respectively, 92.0% and 88.8% of patients had an undetectable plasma HIV-1 RNA level (< or = 400 copies/mL). Kaplan-Meier survival estimates at 1 and 2 years were 96.6% and 95.4%. One hundred twenty patients (18.2%) had treatment-modifying toxicities, of which the most common were lipodystrophy, anemia, neutropenia, and Stevens-Johnson syndrome. There was a trend toward difference in time to treatment-modifying toxicity by pooled dual-NRTI combination and no difference in death rates.
The preliminary study results show overall excellent efficacy and tolerability of NNRTI-based cART among HIV-1 subtype C-infected adults. ZDV/ddI-containing cART, however, is inferior to the dual NRTIs d4T/3TC or ZDV/3TC when used with an NNRTI for first-line cART.
To determine adherence to and effectiveness of antiretroviral therapy (ART) in adolescents vs. adults in southern Africa.
Observational cohort study.
Aid for AIDS, a private sector disease management program in southern Africa.
Adolescents (age 11-19 years; n = 154) and adults (n = 7622) initiating ART between 1999 and 2006 and having a viral load measurement within 1 year after ART initiation.
Primary: virologic suppression (HIV viral load < or = 400 copies/mL), viral rebound, and CD4 T-cell count at 6, 12, 18, and 24 months after ART initiation. Secondary: adherence assessed by pharmacy refills at 6, 12, and 24 months. Multivariate analyses: loglinear regression and Cox proportional hazards.
A significantly smaller proportion of adolescents achieved 100% adherence at each time point (adolescents: 20.7% at 6 months, 14.3% at 12 months, and 6.6% at 24 months; adults: 40.5%, 27.9%, and 20.6% at each time point, respectively; P < 0.01). Patients achieving 100% 12-month adherence were significantly more likely to exhibit virologic suppression at 12 months, regardless of age. However, adolescents achieving virologic suppression had significantly shorter time to viral rebound (adjusted hazard ratio 2.03; 95% confidence interval: 1.31 to 3.13; P < 0.003). Adolescents were less likely to experience long-term immunologic recovery despite initial CD4 T-cell counts comparable to adults.
Compared with adults, adolescents in southern Africa are less adherent to ART and have lower rates of virologic suppression and immunologic recovery and a higher rate of virologic rebound after initial suppression. Studies must determine specific barriers to adherence in this population and develop appropriate interventions.
The relationship between adherence, antiretroviral regimen, and viral load (VL) suppression was assessed through a 1 year prospective follow-up study among 1142 HIV-infected patient. Patients on antiretroviral therapy who attended to the pharmacy during a 6-month period were considered eligible. Those included in the final analysis were patients who had been taking the same antiretroviral therapy for > or =6 months since their inclusion. The cohort included patients taking first line therapy (n = 243) and antiretroviral-experienced patients (n = 899). Naive patients who were included had to have reached undetectable VL at enrollment. Antiretroviral-experienced patients with detectable VL determinations in the previous 6 months were excluded. Adherence was measured by means of announced pill counts and dispensation pharmacy records. Of patients, 58% were taking NNRTI, 31.4% boosted PI, and 10.6% unboosted PI-based regimens. Overall, the relative risk of virologic failure was 9.0 (95% CI 4.0-20.1) in patients with adherence 80-89.9%, 45.6 (95% CI 19.9-104.5) with adherence 70-79.9%, and 77.3 (95% CI 34.2-174.9) with adherence <70%, compared with adherence of > or =90%. The risk of virologic failure in patients with adherence <90% taking unboosted PI was 2.5 times higher than the group taking boosted PI (95% CI 1.2-5.3). There were no statistical differences in patients taking boosted PI and those who were taking NNRTI. Less than 95% of adherence is associated with high virologic success. For patients taking NNRTI- or boosted PI-based regimens with adherence rates of 80%, the failure rate is <10%. These data do not affect the goal of achieving the highest level of adherence possible.
This paper describes an audit of a community-based tuberculosis treatment program involving directly observed therapy in South Africa.
A program audit of 2473 consecutive tuberculosis patients in Hlabisa Health District, KwaZulu/Natal, South Africa, was conducted between 1991 and 1994.
Monthly admissions increased from 34 per month in 1991 to 66 in 1994. Of 2186 patients managed in Hlabisa, 1903 (87%) received directly observed therapy. Of those receiving directly observed therapy, 1034 (55%) were supervised by volunteers; 743 (72%) of these were supervised by storekeepers. Among those patients managed locally, 1679 (85%) of 1967 surviving patients completed treatment. Completion rates for patients supervised by health workers and non-health workers were the same. Completion fell from a high of 90% in 1992 to 78% in 1994. Mortality increased from 5% in 1991 to 10% in 1994.
Community-based directly observed therapy that uses an intermittent drug regime and volunteers as supervisors can achieve high treatment completion rates for tuberculosis, even in resource-poor settings.
In clinical trials, highly active antiretroviral therapy (HAART) reduces plasma HIV-1 RNA levels to less than 500 copies/mL in 60% to 90% of patients with HIV-1 infection. The performance of such therapy outside of the clinical trial setting is unclear.
To determine factors associated with failure to suppress HIV-1 RNA levels and adverse drug reactions in a cohort of patients in whom protease inhibitor-containing therapy was begun in a large urban clinic.
Retrospective cohort study.
Johns Hopkins HIV Clinic in Baltimore, Maryland.
273 protease inhibitor-naive patients began taking a protease inhibitor regimen containing at least one other antiretroviral drug to which the patients had not previously been exposed.
Demographic variables, plasma HIV-1 RNA levels, CD4+ lymphocyte counts, and adverse drug reactions.
Levels of HIV-1 RNA were undetectable in 42% of the cohort at 1 to 90 days, in 44% at 3 to 7 months, and in 37% at 7 to 14 months. Factors associated with failure to suppress viral load at two or more time points included higher rates of missed clinic appointments, nonwhite ethnicity, age 40 years or younger, injection drug use, lower baseline CD4+ lymphocyte count, and higher baseline viral load. In a multivariate model, only higher rates of missed clinic appointments were independently associated with viral suppression at 1 year. Ritonavir was associated with adverse drug reactions about twice as frequently as indinavir or nelfinavir, and women experienced significantly more adverse effects than men.
Unselected patients in whom HAART is started in a clinic setting achieve viral suppression substantially less frequently than do patients in controlled clinical trials. Missed clinic visits were the most important risk factor for failure to suppress HIV-1 RNA levels. Studies are needed to identify interventions that maximize the performance of HAART in inner-city clinics.
The use of protease inhibitor-containing (PI) combination antiretroviral therapy has led to a reduction in the incidence of opportunistic illness and mortality (events) in HIV infection. We wished to quantify the changing incidence of these events in our clinical practice and delineate the relationship between CD4, HIV-1 RNA, and development of events in patients receiving PI combination therapy.
We assessed HIV-infected patients with CD4 counts < or =500 cells x10(6)/l. We calculated the incidence of events from 1994 through 1998 and analyzed the association of temporal changes in event incidence and use of antiretroviral therapy. In patients on PI combination therapy, we determined the probability of achieving and maintaining an undetectable HIV-1 RNA response and determined the association of CD4, HIV-1 RNA, and developing an event.
The incidence of opportunistic illness declined from 23.7 events/100 person-years in 1994 to 14.0 events/100 person-years in 1998 (P<0.001). Mortality declined from 20.2 deaths/100 person-years in 1994 to 8.4 deaths/ 100 person-years in 1998 (P<0.001). Use of PI combination therapy was associated with a relative rate of opportunistic illness or death of 0.66 [95% confidence interval (CI), 0.51-0.85; P<0.001]. The relative incidence of each of 16 opportunistic illnesses was approximately the same in 1998 as in 1994 except for lymphoma, cervical cancer and wasting syndrome which do not appeared to have declined in incidence. Approximately 60% of patients who received PI therapy achieved an undetectable HIV-1 RNA, and 65% of these patients maintained durable suppression of HIV-1 RNA. Achieving an undetectable HIV-1 RNA was associated with a decreased risk of an event, and was the variable most strongly associated with an increase in CD4 level. By multivariate analysis, the concurrent CD4 level was most strongly associated with developing an event.
We observed a significant decline in the incidence of opportunistic illness and death from 1994 through 1998 associated with combination antiretroviral therapy. Patients who develop events while being treated with PI combination therapy were not likely to have achieved an undetectable HIV-1 RNA and are likely to have a low concurrent CD4 level.
This article has no abstract; the first 100 words appear below.
Soon after the acquired immunodeficiency syndrome (AIDS) was first described in 1981,¹–⁴ it became clear that opportunistic infections occurred with remarkable frequency and caused substantial morbidity and mortality among patients with AIDS. On the basis of a series of clinical trials, chemoprophylaxis to prevent initial episodes of certain opportunistic infections (primary prophylaxis) and subsequent episodes (secondary prophylaxis) became the standard of care. The success of highly active antiretroviral therapy (defined as combination antiretroviral regimens that include either a potent viral-protease inhibitor or a nonnucleoside reverse-transcriptase inhibitor) in reducing the incidence of AIDS-related opportunistic infections and consequent morbidity and mortality . . .
Source Information
From the Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, Md.
Address reprint requests to Dr. Masur at the National Institutes of Health, Clinical Center, Critical Care Medicine Department, 10 Center Dr., Bethesda, MD 20892-1662, or at hmasur@nih.gov.
To compare electronically monitored (MEMS) with self-reported adherence in drug users, including the impact of adherence on
HIV load, we conducted a 6-month observational study of 67 antiretroviral-experienced current and former drug users. Adherence
(percentage of doses taken as prescribed) was calculated for both the day and the week preceding each of 6 research visits.
Mean self-reported 1-day adherence was 79% (median, 86%), and mean self-reported 1-week adherence was 78% (median, 85%). Mean
MEMS 1-day adherence was 57% (median, 52%), and mean MEMS 1-week adherence was 53% (median, 49%). One-day and 1-week estimates
were highly correlated (r > .8 for both measures). Both self-reported and MEMS adherence were correlated with concurrent HIV load (r = .43–.60), but the likelihood of achieving virologic suppression was greater if MEMS adherence was high than if self-reported
adherence was high. We conclude that self-reported adherence is higher than MEMS adherence, but a strong relationship exists
between both measures and virus load. However, electronic monitoring is more sensitive than self-report for the detection
of nonadherence and should be used in adherence intervention studies.
To characterize the impact of intermittent use of triple drug antiretroviral therapy on survival.
Population-based analysis of 1282 antiretroviral therapy naive HIV-positive individuals aged 18 years and older in British Columbia who started triple-combination therapy between August 1996 and December 1999. Therapy use was estimated by dividing the number of months of medications dispensed by the number of months of follow-up. Intermittent therapy was defined as the participant having obtained less than 75% of their medication in the first 12 months.
Cumulative all-cause mortality rates from the start of triple drug antiretroviral therapy to 30 September 2000.
As of 30 September 2000, 106 subjects had died. Cumulative mortality was 3.9% (+/- 0.5%) at 12 months. In a multivariate model, after controlling for other variables that were significant in the univariate analyses each 100 cell decrement in baseline CD4 cell count and the intermittent use of antiretroviral drugs were associated with increased mortality with risk ratios of 1.31 [95% confidence interval (CI), 1.16-1.49; P < 0.001] and 2.90 (95% CI, 1.93-4.36; P < 0.001), respectively. In order to control for downward drift, intermittent use of therapy was measured over the first year whereas other factors were measured at the end of year 1. After adjusting for all other factors, those participants who used antiretroviral drugs intermittently were 2.97 times (95% CI, 1.33-6.62; P = 0.008) more likely to die.
Our study demonstrates that even after adjusting for other prognostic factors intermittent use of antiretroviral therapy was associated with increased mortality.
Injection drug users (IDUs) who are in a methadone maintenance therapy program are required to attend their drug treatment clinic on a regular basis for directly observed therapy (DOT). Such programs provide a unique opportunity to administer HAART to HIV-infected persons in this marginalized population in conjunction with their methadone therapy. A prospective observational study was conducted to determine the efficacy of directly observed antiretroviral therapy provided in conjunction with daily observed methadone maintenance therapy. A cohort of 39 patients was enrolled to receive HAART as DOT. At 48 weeks, 51% of antiretroviral-experienced patients and 65% of antiretroviral-naive patients had achieved maximum viral suppression. DOT should therefore be considered a potential option for providing HAART to IDUs, particularly when used in conjunction with methadone maintenance therapy.
While combination antiretroviral treatment has had a profound impact on the morbidity and mortality of human immunodeficiency virus (HIV) infection, the adherence demands of this therapy are high and failure to maintain viral suppression is common. Directly administered antiretroviral therapy (DAART) has garnered attention recently as a strategy to improve medication adherence and clinical outcomes in HIV-infected individuals. This review is intended to provide an update on the use of DAART and the challenges posed by this strategy, explore settings in which DAART may be used, discuss the role of antiretroviral regimens with improved pharmacokinetic features, and propose future directions for DAART strategies. DAART is modeled on directly observed therapy (DOT) for the treatment of tuberculosis. However, differences in curability, medication dosing frequency, duration of treatment, and the biologic dynamics of infection, pose unique challenges to DAART strategies. Numerous settings have been proposed for DAART, including community based outreach programs, prisons, long-term care facilities, substance abuse treatment sites, and resource-poor countries. Experience with DAART to date has been limited to pilot studies or retrospective comparisons. The prospect of simplified, once-daily antiretroviral therapy holds promise for DAART. However, improvements in antiretroviral therapy may also improve outcomes in patients taking therapy on a self-administered basis. Randomized controlled trials of DAART are needed before this strategy can be embraced in any setting. In future studies it will be important to compare DAART with self-administered therapy in terms of initial virologic and immunologic responses, durability of responses, the development of antiretroviral resistance, and cost effectiveness.
To determine adherence of an indigent African HIV-infected cohort initiating antiretroviral therapy (ART); to identify predictors of incomplete adherence (< 95%) and virologic failure (> 400 HIV RNA copies/ml).
Prospective monitoring of adherence in a poor HIV-positive cohort, attending a public sector hospital and receiving ART through phase III studies.
Adherence to ART was determined over 48 weeks by counting tablet-returns. Logistic regression models including age, WHO HIV stage, home language, socio-economic status, complexity and type of regimen were fitted to determine predictors of incomplete adherence and virologic failure at 48 weeks.
289 patients were recruited between January 1996 and May 2001. Median (mean) adherence of the cohort was 93.5% (87.2%). Three times daily dosing [risk ratio (RR), 3.07; 95% confidence interval (CI), 1.40-6.74], speaking English (RR, 0.41; 95% CI, 0.21-0.80) and age (RR, 0.97; 95% CI, 0.94-0.99) were independent predictors of incomplete adherence. Socio-economic status, sex and HIV stage did not predict adherence. Independent predictors of virologic failure included baseline viral load (RR, 2.57; 95% CI, 1.57-4.22) and three times daily dosing (RR, 2.64; 95% CI, 1.23-5.66), incomplete adherence (RR, 1.92; 95% CI, 1.10-3.57), age (RR, 0.96; 95% CI, 0.92-0.99) and dual nucleoside therapy (RR, 2.69; 95% CI, 1.17-6.15).
The proportion of individuals achieving viral suppression matched results from the developing world. Speaking the same language as site staff and simplified dosing frequency were beneficial. Socio-economic status had no impact on adherence and should not be used as a limitation to ART access.
Access to programmes providing highly active antiretroviral therapy (HAART) is recent in Africa. In Senegal, a national initiative was launched in 1998. The capacity of African patients to adhere to complex antiretroviral treatments (ARV) is largely unknown.
We assessed adherence and identified the main reasons for treatment interruption in a prospective observational cohort of patients participating in an ARV access programme in Dakar, Senegal. Adherence was estimated each month on the basis of the patients' stated consumption and on the proportion of the prescribed dose returned unused to the dispensing pharmacy. A total of 158 patients were studied between November 1999 and October 2001.
A cross-section analysis showed that the stated level of adherence was high: on average, over the study period, the patients said they had taken 91% of each monthly dose and that they had taken the full monthly dose during two-thirds of the months studied. Adherence tended to be better among patients who were required to make little or no contribution to the cost of their treatment, through an appropriate pricing structure. Adherence was also better with efavirenz-containing regimens than with indinavir-containing regimens.
These results show that adherence to HAART can be as high in Africa as that generally observed in industrialized countries, and that the cost and type of drug regimen must be taken into account when designing ARV access programmes for poor communities.
Botswana has the highest rate of HIV infection in the world, estimated at 36% among the population aged 15-49 years. To improve antiretroviral (ARV) treatment delivery, we conducted a cross-sectional study of the social, cultural, and structural determinants of treatment adherence.
We used both qualitative and quantitative research methodologies, including questionnaires and interviews with patients receiving ARV treatment and their health care providers to elicit principal barriers to adherence. Patient report and provider estimate of adherence (>/=95% doses) were the primary outcomes.
One hundred nine patients and 60 health care providers were interviewed between January and July 2000; 54% of patients were adherent by self-report, while 56% were adherent by provider assessment. Observed agreement between patients and providers was 68%. Principal barriers to adherence included financial constraints (44%), stigma (15%), travel/migration (10%), and side effects (9%). On the basis of logistic regression, if cost were removed as a barrier, adherence is predicted to increase from 54% to 74%.
ARV adherence rates in this study were comparable with those seen in developed countries. As elsewhere, health care providers in Botswana were often unable to identify which patients adhere to their ARV regimens. The cost of ARV therapy was the most significant barrier to adherence.
Brazil provides antiretroviral therapy (ART) to HIV-infected persons free of charge. The objective of this study was to investigate factors associated with ART failure in patients receiving free ART in public clinics in Brazil.
This is a cross-sectional study of adults taking ART for 6 to 24 months in 5 public clinics in Rio de Janeiro. Patients were interviewed and their charts were reviewed. The following definitions of response to therapy at 6 months were used: virologic responders (VR), > or =1 log reduction in plasma viral load (VL); immunologic responders (IR), increase of > or = 50 CD4 cells/mL; complete responders (CR), both VR and IR; and nonresponders (NR), neither VR nor IR.
Of 211 patients enrolled, 173 (82%) were VR, IR, or CR and 38 (18%) were NR. Of the responders, 28 (13%) were IR, 32 (15%) were VR, and 113 (53%) were CR. In multivariate analysis, factors associated with NR were less than 80% adherence (OR = 8.6; 95% CI, 2.9-25.7), baseline CD4 count (OR = 0.5 per 50 cells/mL; 95% CI, 0.2-1.1), interval between starting ART and first VL/CD4 testing (OR = 1.4 for each month; 95% CI, 1.1-1.8), opportunistic disease after starting ART (OR = 6.8; 95% CI, 1.4-34.0), inability to read prescription (OR = 3.9; 95% CI, 1.4-10.9), not believing physician is knowledgeable about HIV (OR = 4.0; 95% CI, 1.1-15.0), not having a friend with HIV (OR = 6.1; 95% CI, 1.7-21.8), believing ART will make him/her ill (OR = 5.6; 95% CI, 1.7-18.8), and believing ART will delay HIV progression (OR = 0.001; 95% CI, 0.0-0.2).
The proportion of patients responding to ART in Brazil was similar to reports from developed countries, suggesting that ART can be used successfully in developing countries. Variables related to adherence, knowledge, and perceptions about ART were associated with a lack of response to ART. These findings have important implications for developing nations that are considering increased access to ART.
To determine the feasibility and effectiveness of integrating highly active antiretroviral therapy (HAART) into existing tuberculosis directly observed therapy (TB/DOT) programs, we performed a pilot study in an urban TB clinic in South Africa. Patients with smear-positive pulmonary TB were offered HIV counseling and testing. Twenty HIV-positive patients received once-daily didanosine (400 mg) plus lamivudine (300 mg) plus efavirenz (600 mg) administered concomitantly with standard TB therapy Monday to Friday and self-administered on weekends. After completing TB therapy, patients were referred to an HIV clinic for continued treatment. At baseline, patients had a mean CD4 count of 230 cells/mm(3) (range: 24-499 cells/mm(3)) and a mean viral load of 5.75 log(10) (range: 3.81-7.53 log(10)). Seventeen completed combined standard TB and HIV therapy; 16 of 20 (80%) patients enrolled and 15 of 17 (88%) patients completing standard TB therapy achieved a viral load <50 copies/mL and mean CD4 count increase of 148 cells/mm(3). TB was cured in 17 of 20 (85%) enrolled patients and 17 of 19 (89%) patients with drug-sensitive TB. Treatment was well tolerated, with minimal gastrointestinal, hepatic, skin, or neurologic toxicity. The project was well accepted and integrated into the daily TB clinic functions. This pilot study demonstrates that TB/DOT programs can be feasible and effective sites for HIV identification and the introduction and monitoring of a once-daily HAART regimen in resource-limited settings.
Little is known about achievable levels of antiretroviral treatment (ART) adherence in resource-limited settings. We conducted a cross-sectional study of adherence among patients at Chris Hani Baragwanath Hospital's Adult HIV Clinic in Soweto, South Africa. Adherence was assessed using a 1-month, self-report questionnaire and was calculated as a ratio of doses taken to doses prescribed. The 66 patients studied had a mean age of 36.1 years, a median duration of ART use of 18 months, and an overall baseline median CD4(+) cell count of 200/mm(3) (IQR: 114-364). The adherence reported by these patients for the previous month was >95% for 58 patients (88%), 90-95% for 6 (9%) and, < 90% for 2 (3%). The main reasons given for missing doses were being away from home (30%), difficulty with the dosing schedules (23%), and running out of pills (12%). Adherence decreased considerably with fear of being stigmatized by the sexual partner (OR = 0.13 95%, CI 0.02-0.70). Plasma HIV RNA levels were <400 copies/ml in the majority of patients (73% of those with adherence >95% and 88% of patients with < or =95% adherence) and the overall median CD4(+) cell count rose to 324/mm(3) (IQR: 193-510). High adherence and viral suppression are achievable for a significant proportion of HIV-infected patients taking ART in a resource-limited area such as Soweto, South Africa. Strategies to maximize adherence in this setting should emphasize ready access to affordable and simple ART regimens, as well as HIV education programs to help increase awareness and decrease disease stigmatization.
World AIDS Day last month focused on the impact of HIV on women and girls. The particular vulnerability of women to HIV during and after conflict is well-recognised. Yet conflict-affected communities have been excluded from international discourse around AIDS care and funding for treatment in resource-poor settings. Of more than 10 000 abstracts published for the 2004 International AIDS Conference in Bangkok only one reported on treatment of AIDS in a conflict setting. One in four African countries many with a high prevalence of HIV are currently affected by conflict. In the Democratic Republic of Congo alone 24 million people are directly affected by conflict and almost 4 million are displaced. Even in apparently stable countries and communities AIDS treatment programmes can experience instability and conflict in the coming years—the risk exacerbated by poverty and HIV. (excerpt)
Farms in the Boland health district, Western Cape Province, South Africa.
To evaluate the effect of lay health workers (LHWs) on tuberculosis (TB) control among permanent farm workers and farm dwellers in an area with particularly high TB prevalence.
Pragmatic, unblinded cluster randomised control trial.
This trial measured successful treatment completion rates among new smear-positive (NSP) adult TB patients on 106 intervention farms, and compared them with outcomes in patients on 105 control farms. Farms were the unit of randomisation, and analysis was by intention to treat.
A total of 164 adult TB patients were recruited into the study, 89 of whom were NSP. The successful treatment completion rate in NSP adult TB patients was 18.7% higher (P = 0.042, 95%CI 0.9-36.4) on farms in the intervention group than on farms in the control group. Case finding for adult NSP TB cases was 8% higher (P = 0.2671) on farms in the intervention group compared to the control group.
Trained LHWs were able to improve the successful TB treatment rate among adult NSP TB patients in a well-established health service, despite reduction of services.
Medication adherence is essential to successful treatment of HIV/AIDS. Maintaining high adherence will likely prove a major challenge in Africa -- just as it has in developed nations. Despite early reports suggesting that adherence would not pose a major barrier to treatment success, more recent research shows that adherence rates in Africa are quite variable and often poor. Given the large number of patients whose disease will progress if adherence is suboptimal, research is urgently needed to determine patient-level behavioral barriers to adherence and the most effective and appropriate methods for assessing adherence in African cohorts.
To compare the prevalence of resistance by adherence level in patients treated with non-nucleoside reverse transcriptase inhibitors (NNRTI) or protease inhibitors (PI). Also to examine the mechanism of differential class-specific adherence-resistance relationships, focusing on the patient-derived capacity of wild-type and drug-resistant recombinant variants to replicate in vitro in the presence of variable drug levels.
Participants received unannounced pill count measures to assess adherence, viral load monitoring, and genotypic resistance testing. The replicative capacity of drug-susceptible and drug-resistant recombinants was determined using a single-cycle recombinant phenotypic susceptibility assay. Drug exposure was estimated using population-averaged pharmacological measurements adjusted by participant-specific levels of adherence.
In the NNRTI-treated group, 69% had resistance at 0-48% adherence compared to 13% at 95-100% (P = 0.01). PI resistance was less common than NNRTI resistance at 0-48% adherence (69% versus 23%; P = 0.01). In multivariate analysis, the odds for PI resistance increased (P = 0.03) while the odds for NNRTI resistance decreased (P = 0.04) with improving adherence. Individuals with drug-resistant variants were more likely to have levels of drug exposure where the resistant variant was more fit than the drug-susceptible variant in vitro, while those with drug-susceptible virus were more likely to have levels of drug exposure where the drug-susceptible virus was more fit than the drug-resistant variant (P = 0.005).
NNRTI resistance was more common than PI resistance at low levels of adherence. Class-specific adherence-resistance relationships are associated with the relative replicative capacity of drug-resistant versus wild-type variants to replicate in the presence of clinically relevant drug levels.
To conduct a quantitative review of published trials of antiretroviral therapy (ART) adherence interventions.
A research synthesis of published ART adherence intervention outcome studies.
ART adherence intervention outcome studies meeting inclusion criteria published between 1996 and December 2004 (k=24).
Effect sizes (ESs [d]) were calculated for each study outcome, producing 25 immediate postintervention outcomes and an additional 13 follow-up ESs. Reported pre- to post-ART adherence between groups (k = 15) or within groups (k = 10) served as the main outcome converted to standardized ES.
ART adherence interventions had a small effect (d = 0.35, odds ratio [OR] = 1.88) that varied considerably across studies. Interventions that specifically enrolled participants with known or anticipated problems with ART adherence demonstrated medium effects on adherence (d = 0.62, OR = 3.07). Interventions that did not target their participants on similar criteria had quite small effects(d = 0.19, OR = 1.41). Adherence improvements showed no tendency to decay across time.
Outcomes of studies targeting those with poor ART adherence had stronger effects than those intervening with groups of individuals who were mixed in terms of pretest levels of adherence. Adherence intervention outcome studies must carefully delineate their target populations, because defining individuals as "on ART" does not provide the level of specificity needed to design and implement effective interventions.
Background:
A key component of the DOTS strategy for tuberculosis control (short-course chemotherapy following WHO guidelines) is direct observation of treatment. WHO technical guidelines recommend that health workers should undertake this part of the strategy, but will also accept direct observation of treatment in the community; WHO does not think that a family member should undertake this role. Supporting evidence for these recommendations is not available. The Nepal national tuberculosis programme asked us to develop and test a strategy of direct observation of treatment for the hill districts of Nepal, where direct observation of treatment by health workers is not feasible. We aimed to assess the success rates of two DOTS strategies developed for such areas.
Methods:
Between mid-July, 2002, and mid-July, 2003, we undertook a cluster-randomised controlled trial to compare two strategies-community DOTS and family-member DOTS--in ten hill and mountain districts of Nepal. Districts were used as the unit of randomisation. Primary outcome was success rate (proportion of registered patients who achieved cure or completed treatment), and analysis was by intention to treat.
Findings:
Five districts (549 patients) were allocated to community DOTS and five (358 patients) were allocated family-member DOTS. Community DOTS and family-member DOTS achieved success rates of 85% and 89%, respectively (odds ratio of success for community DOTS relative to family-member DOTS, 0.67 [95% CI 0.41-1.10]; p=0.09). Estimated case-finding rates were 63% with the community strategy and 44% with family-member DOTS.
Interpretation:
The family-member DOTS and community DOTS strategies can both attain international targets for treatment success under programme conditions, and thus are appropriate for the hill and mountain districts of Nepal. Both strategies might also be appropriate in other parts of the world where directly observed treatment by health workers is not feasible. Our findings lend support to adoption of this patient-responsive approach to direct observation of treatment within global tuberculosis control policy.
Directly administered antiretroviral therapy (DAART) in methadone clinics has the potential to improve treatment outcomes for human immunodeficiency virus (HIV)-infected injection drug users (IDUs).
DAART was provided at 3 urban methadone clinics. Eighty-two participants who were initiating or reinitiating highly active antiretroviral therapy (HAART) received supervised doses of therapy at the clinic on the mornings on which they received methadone. Treatment outcomes in the DAART group were compared with outcomes in 3 groups of concurrent comparison patients, who were drawn from the Johns Hopkins HIV Cohort. The concurrent comparison patients were taking HAART on a self-administered basis. The 3 groups of concurrent comparison patients were as follows: patients with a history of IDU who were receiving methadone at the time HAART was used (the IDU-methadone group; 75 patients), patients with a history of IDU who were not receiving methadone at the time that HAART was used (the IDU-nonmethadone group; 244 patients), and patients with no history of IDU (the non-IDU group; 490 patients).
At 12 months, 56% of DAART participants achieved an HIV type 1 RNA level <400 copies/mL, compared with 32% of participants in the IDU-methadone group (P=.009), 33% of those in the IDU-nonmethadone group (P=.001), and 44% of those in the non-IDU group (P=.077). The DAART group experienced a median increase in the CD4 cell count of 74 cells/mm3, compared with 21 cells/mm3 in the IDU-methadone group (P=.04), 33 cells/mm3 in the IDU-nonmethadone group (P=.09), and 84 cells/mm3 in the non-IDU group (P=.98). After adjustment for other covariates in a logistic regression model, DAART participants were significantly more likely to achieve viral suppression than were patients in each of the 3 comparison groups.
These results suggest that methadone clinic-based DAART has the potential to provide substantial clinical benefit for HIV-infected IDUs.