A Systematic Review on Promoting Adherence to Antiretroviral Therapy in HIV-infected Patients Using Mobile Phone Technology

ArticleinApplied Clinical Informatics 09(02):450-466 · April 2018with 68 Reads
Abstract
Objective Adherence to antiretroviral therapy (ART) is paramount to successful long-term suppression of human immunodeficiency virus (HIV). For poorly adherent patients with HIV, barriers to remaining adherent may be overcome by the implementation of targeted interventions delivered via mobile devices. This systematic review is focused specifically on mobile phone technologies to deliver adherence interventions in HIV/acquired immunodeficiency syndrome (AIDS) populations. Methods This review (PROSPERO #CRD42017065131) systematically extracted data from published literature from five databases on mobile phone interventions to improve adherence to ART for HIV. The reported studies had been conducted between 2007 and 2017. Risk of bias was assessed using the Cochrane method ranking each criterion as low, high, or unclear risk of bias. Results Of the 835 articles returned, we identified 26 randomized controlled trials (RCTs), retrospective and prospective cohort trials, or mixed method studies with a comparison group that fit criteria for inclusion. No standard measure of adherence was consistent throughout the examined studies, and assessments by self-report, pill counting, and medication event monitoring system (MEMS) were utilized. The studies reported mixed results, with 17 reporting significant improvements to adherence, 3 reporting improvements without supplying p-values, and 6 reporting no significant change or a reduction in adherence. Conclusion The mixed nature of the results exemplifies the need for more comprehensive approaches and larger scale trials to confirm results observed in limited cohort sizes. To better retain satisfactory adherence within the HIV population, and especially in low-resource settings, we recommend that future interventions incorporate multiple strategies: mobile-based reminders, social support structures, and personalized content.
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    Real-time adherence monitoring is now possible through medication storage devices equipped with cellular technology. We assessed the effect of triggered cell phone reminders and counseling utilizing objective adherence data on antiretroviral (ART) adherence among Chinese HIV-infected patients. We provided ART patients in Nanning, China, with a medication device ("Wisepill") to monitor their ART adherence electronically. After 3 months, we randomized subjects within optimal (≥95%) and suboptimal (<95%) adherence strata to intervention vs. control arms. In months 4-9, intervention subjects received individualized reminders triggered by late dose-taking (no device-opening by 30 minutes past dose time), and counseling using device-generated data. Controls received no reminders or data-informed counseling. We compared post-intervention proportions achieving optimal adherence, mean adherence, and clinical outcomes. Of 120 subjects enrolled, 116 (96.7%) completed the trial. Pre-intervention, optimal adherence was similar in intervention vs. control arms (63.5% vs. 58.9%, respectively; p=0.60). In the last intervention month, 87.3% vs. 51.8% achieved optimal adherence (risk ratio (RR) 1.7, 95% Confidence Interval (CI) 1.3-2.2); mean adherence was 96.2% vs. 89.1% (p=0.003). Among pre-intervention suboptimal adherers, 78.3% vs. 33.3% (RR 2.4, CI 1.2-4.5) achieved optimal adherence; mean adherence was 93.3% vs. 84.7% (p=0.039). Proportions were 92.5% and 62.9% among optimal adherers, respectively (RR 1.5, CI 1.1-1.9); mean adherence was 97.8% vs. 91.7% (p=0.028). Post-intervention clinical outcomes were not significant. Real-time reminders significantly improved ART adherence in this population. This approach appears promising for managing HIV and other chronic diseases and warrants further investigation and adaptation in other settings.
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    The aim of this systematic review of reviews is to identify mobile text-messaging interventions designed for health improvement and behavior change and to derive recommendations for practice. We have compiled and reviewed existing systematic research reviews and meta-analyses to organize and summarize the text-messaging intervention evidence base, identify best-practice recommendations based on findings from multiple reviews, and explore implications for future research. Our review found that the majority of published text-messaging interventions were effective when addressing diabetes self-management, weight loss, physical activity, smoking cessation, and medication adherence for antiretroviral therapy. However, we found limited evidence across the population of studies and reviews to inform recommended intervention characteristics. Although strong evidence supports the value of integrating text-messaging interventions into public health practice, additional research is needed to establish longer-term intervention effects, identify recommended intervention characteristics, and explore issues of cost-effectiveness.
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    Less than one-third of HIV-infected pregnant women eligible for combination antiretroviral therapy (ART) globally initiate treatment prior to delivery, with lack of access to timely CD4 results being a principal barrier. We evaluated the effectiveness of an SMS-based intervention to improve access to timely antenatal ART.We conducted a stepped-wedge cluster randomized trial of a low-cost programmatic intervention in 20 antenatal clinics in Gaborone, Botswana. From July 2011-April 2012, 2 clinics were randomly selected every 4 weeks to receive an ongoing clinic-based educational intervention to improve CD4 collection and to receive CD4 results via an automated SMS platform with active patient tracing. CD4 testing before 26 weeks gestation and ART initiation before 30 weeks gestation were assessed.Three-hundred-sixty-six ART-naïve women were included, 189 registering for antenatal care under Intervention and 177 under Usual Care periods. Of CD4-eligible women, 100 (59.2%) women under Intervention and 79 (50.6%) women under Usual Care completed CD4 phlebotomy before 26 weeks gestation, adjusted odds ratio (aOR, adjusted for time that a clinic initiated Intervention) 0.87 (95% confidence interval [CI]0.47-1.63, P = 0.67). The SMS-based platform reduced time to clinic receipt of CD4 test result from median of 16 to 6 days (P
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    Background: Optimal adherence is critical to achieve the benefits of antiretroviral treatment (ART). The aim of the study is to evaluate the use of mobile devices as a strategy to improve adherence to ART, measured by Viral Load (VL) in HIV+ patients less than 25 years of age. Methods: A prospective study was conducted in a cohort of HIV+ patients less than 25 years of age. HIV+ patients, on ART, VL >1000 copies/mL, using mobile devices and suboptimal adherence (SOA) were included. The intervention was based on a mobile generic contact twice a month using text message and Facebook during 32 weeks. Extended communications were generated by the patient. VL was performed before and after the intervention. Results: 25 patients were included. Three were excluded and 22 patients were enrolled. Mean age was 17.2 ± 6.1 years (range: 6-25); 15(68%) were female; mean baseline VL was 25,100copies/mL (range: 500,000-1,020copies/mL), mean log was 4.3(Range: 3-5.7log). Each participant received a total of 16 contacts, 84% (296) were answered by the patient. 54%(189) of the contacts generated extended communications. After the strategy implementation 20/22 VL results were available. 13/20 (65%) were undetectable, 14/20 (70%) had VL < 1000 copies/mL. 6/20 (30%) VLs had no changes. Conclusions: The use of mobile devices and social networks is a valid tool to improve ART adherence in pediatric and young adults HIV+ patients, evaluated through VL. The strategy is feasible. The reminder messages trigger additional communications between patients and health provider and better engagement with HIV care. Longer follow up time is needed.
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    AimsAdherence to medication is a major problem that affects 50-60% of chronically ill patients. As mobile phone use spreads rapidly, a new model of remote health delivery via mobile phone - mHealth - is increasingly used. The objective of this study is to provide a comprehensive overview of how mHealth can be used to improve adherence to medication. MethodsA systematic literature review was conducted using four databases (CINAHL, PubMed, Scopus and PsycARTICLES). Eligible articles available on March 2014 had to be written in English or Spanish and have a comparative design. Articles were reviewed by two authors independently. A Cochrane Collaboration tool was used to assess the studies based on their internal validity. ResultsOf the 1504 articles found, 20 fulfilled the inclusion criteria [13 randomised clinical trials (RCT), one quasi-RCT, one non-randomised parallel group study and five studies with a pre-post design]. Nearly all the trials were conducted in high-income countries (80.0%). Articles were categorised depending on the target population into three different groups: (i) HIV-infected patients, n=5; (ii) patients with other chronic diseases (asthma, coronary heart disease, diabetes mellitus, hypertension, infectious diseases, transplant recipients and psoriasis), n=11; and (iii) healthy individuals, n=4. Adherence improved in four of the studies on HIV-infected patients, in eight of the studies on patients with other chronic diseases, and in 1 study performed in healthy individuals. All studies reported sending SMS as medication reminders, healthy lifestyle reminders, or both. Only one trial (HIV-infected patients) had a low risk of bias. Conclusions Our results showed mixed evidence regarding the benefits of interventions because of the variety of the study designs and the results found. Nevertheless, the interventions do seem to have been beneficial, as 65% of the studies had positive outcomes. Therefore, more high-quality studies should be conducted.
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    Abstract Poor adherence to combination antiretroviral therapy (ART) is a major global challenge. In this study we examined the efficacy of a smartphone application incorporating personalized health-related visual imagery that provided real-time information about the level of medication and the patient's level of immunoprotection, in order to improve adherence to ART. We randomized 28 people on ART to either a standard or augmented version of the smartphone application. The augmented version contained components that illustrated participants' current estimated plasma concentrations of antiretroviral drugs and the immune protection provided by ART. Adherence to ART was assessed at baseline and at 3 months using self-reported adherence, pharmacy dispensing records, and HIV viral load. Information was also collected on illness and medication beliefs and use of the application. Participants who received the augmented application showed a significantly higher level of self-reported adherence to ART at three months (p=0.03) and decreased viral load (p=0.023) as compared to individuals using the standard version. Greater usage of the extra components of the augmented application was associated with greater perceived understanding of HIV infection and increased perceived necessity for ART. Smartphone applications that incorporate personalized health-related visual imagery may have potential to improve adherence to ART.
  • Article
    Importance Medication nonadherence, which has been estimated to affect 28% to 31% of US patients with hypertension, hyperlipidemia, and diabetes, may be improved by electronic medication packaging (EMP) devices (adherence-monitoring devices incorporated into the packaging of a prescription medication).Objectives To investigate whether EMP devices are associated with improved adherence and to identify and describe common features of EMP devices.Evidence Review Systematic review of peer-reviewed studies testing the effectiveness of EMP systems in the MEDLINE, EMBASE, PsycINFO, CINAHL, International Pharmaceutical Abstracts, and Sociological Abstracts databases from searches conducted to June 13, 2014, with extraction of associations between the interventions and adherence, as well as other key findings. Each study was assessed for bias using the Cochrane Handbook for Systematic Reviews of Interventions; features of EMP devices and interventions were qualitatively assessed.Findings Thirty-seven studies (32 randomized and 5 nonrandomized) including 4326 patients met inclusion criteria (10 patient interface–only “simple” interventions and 29 “complex” interventions integrated into the health care system [2 qualified for both categories]). Overall, the effect estimates for differences in mean adherence ranged from a decrease of 2.9% to an increase of 34.0%, and the those for differences in the proportion of patients defined as adherent ranged from a decrease of 8.0% to an increase of 49.5%. We identified 5 common EMP characteristics: recorded dosing events and stored records of adherence, audiovisual reminders to cue dosing, digital displays, real-time monitoring, and feedback on adherence performance.Conclusions and Relevance Many varieties of EMP devices exist. However, data supporting their use are limited, with variability in the quality of studies testing EMP devices. Devices integrated into the care delivery system and designed to record dosing events are most frequently associated with improved adherence, compared with other devices. Higher-quality evidence is needed to determine the effect, if any, of these low-cost interventions on medication nonadherence and to identify their most useful components.
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  • Article
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    Introduction: Access to antiretroviral treatment (ART) has substantially improved over the past decade. In this new era of HIV as a chronic disease, the continued success of ART will depend critically on sustained high ART adherence. The objective of this review was to systematically review interventions that can improve adherence to ART, including individual-level interventions and changes to the structure of ART delivery, to inform the evidence base for the 2013 WHO consolidated antiretroviral guidelines. Design: A rapid systematic review. Methods: We conducted a rapid systematic review of the global evidence on interventions to improve adherence to ART, utilizing pre-existing systematic reviews to identify relevant research evidence complemented by screening of databases for articles published over the past 2 years on evidence from randomized controlled trials (RCTs). We searched five databases for both systematic reviews and primary RCT studies (Cochrane Library, EMBASE, MEDLINE, Web of Science, and WHO Global Health Library); we additionally searched ClinicalTrials.gov for RCT studies. We examined intervention effectiveness by different study characteristics, in particular, the specific populations who received the intervention. Results: A total of 124 studies met our selection criteria. Eighty-six studies were RCTs. More than 20 studies have tested the effectiveness of each of the following interventions, either singly or in combination with other interventions: cognitive-behavioural interventions, education, treatment supporters, directly observed therapy, and active adherence reminder devices (such as mobile phone text messages). Although there is strong evidence that all five of these interventions can significantly increase ART adherence in some settings, each intervention has also been found not to produce significant effects in several studies. Almost half (55) of the 124 studies investigated the effectiveness of combination interventions. Combination interventions tended to have effects that were similar to those of single interventions. The evidence base on interventions in key populations was weak, with the exception of interventions for people who inject drugs. Conclusion: Tested and effective adherence-enhancing interventions should be increasingly moved into implementation in routine programme and care settings, accompanied by rigorous evaluation of implementation impact and performance. Major evidence gaps on adherence-enhancing interventions remain, in particular, on the cost-effectiveness of interventions in different settings, long-term effectiveness, and effectiveness of interventions in specific populations, such as pregnant and breastfeeding women.
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    Access to mobile phone technology has rapidly expanded in developing countries. In Africa, mHealth is a relatively new concept and questions arise regarding reliability of the technology used for health outcomes. This review documents strengths, weaknesses, opportunities, and threats (SWOT) of mHealth projects in Africa. A systematic review of peer-reviewed literature on mHealth projects in Africa, between 2003 and 2013, was carried out using PubMed and OvidSP. Data was synthesized using a SWOT analysis methodology. Results were grouped to assess specific aspects of project implementation in terms of sustainability and mid/long-term results, integration to the health system, management process, scale-up and replication, and legal issues, regulations and standards. Forty-four studies on mHealth projects in Africa were included and classified as: "patient follow-up and medication adherence" (n = 19), "staff training, support and motivation" (n = 2), "staff evaluation, monitoring and guidelines compliance" (n = 4), "drug supply-chain and stock management" (n = 2), "patient education and awareness" (n = 1), "disease surveillance and intervention monitoring" (n = 4), "data collection/transfer and reporting" (n = 10) and "overview of mHealth projects" (n = 2). In general, mHealth projects demonstrate positive health-related outcomes and their success is based on the accessibility, acceptance and low-cost of the technology, effective adaptation to local contexts, strong stakeholder collaboration, and government involvement. Threats such as dependency on funding, unclear healthcare system responsibilities, unreliable infrastructure and lack of evidence on cost-effectiveness challenge their implementation. mHealth projects can potentially be scaled-up to help tackle problems faced by healthcare systems like poor management of drug stocks, weak surveillance and reporting systems or lack of resources. mHealth in Africa is an innovative approach to delivering health services. In this fast-growing technological field, research opportunities include assessing implications of scaling-up mHealth projects, evaluating cost-effectiveness and impacts on the overall health system.
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    This systematic review assesses the published literature to describe the landscape of mobile health technology (mHealth) for HIV/AIDS and the evidence supporting the use of these tools to address the HIV prevention, care, and treatment cascade. The speed of innovation, broad range of initiatives and tools, and heterogeneity in reporting have made it difficult to uncover and synthesize knowledge on how mHealth tools might be effective in addressing the HIV pandemic. To do address this gap, a team of reviewers collected literature on the use of mobile technology for HIV/AIDS among health, engineering, and social science literature databases and analyzed a final set of 62 articles. Articles were systematically coded, assessed for scientific rigor, and sorted for HIV programmatic relevance. The review revealed evidence that mHealth tools support HIV programmatic priorities, including: linkage to care, retention in care, and adherence to antiretroviral treatment. In terms of technical features, mHealth tools facilitate alerts and reminders, data collection, direct voice communication, educational messaging, information on demand, and more. Studies were mostly descriptive with a growing number of quasi-experimental and experimental designs. There was a lack of evidence around the use of mHealth tools to address the needs of key populations, including pregnant mothers, sex workers, users of injection drugs, and men who have sex with men. The science and practice of mHealth for HIV are evolving rapidly, but still in their early stages. Small-scale efforts, pilot projects, and preliminary descriptive studies are advancing and there is a promising trend toward implementing mHealth innovation that is feasible and acceptable within low-resource settings, positive program outcomes, operational improvements, and rigorous study design
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    Context: Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome (HIV/AIDS) is one of the world's most challenging pandemics. For treatment with Highly Active Anti-Retroviral Therapy (HAART) to be effective, high rate of adherence is essential. Aim: To demonstrate the effect of adherence counseling and text message reminders in improving patients' adherence to HAART. Settings and Design: A randomized control trial among non-adherents was carried out in a tertiary hospital in Nigeria between March and July, 2011. Materials and Methods: A total of 104 patients: 45 males (43.3%) and 59 females (56.7%) participated in the study. They were randomized into intervention and control groups. The intervention group received monthly adherence counseling and twice weekly short message reminders for four months, while the control group received only standard care. Self-reported adherence and CD4+ cell counts were measured pre- and post-intervention. Statistical Analysis Used: Data was analysed using Statistical Package for Social Sciences (SPSS) version 18. Risk rates, Chi-square, Mann-Whitney U test and Cohen's effect size were calculated. Level of significance was set at P = 0.05. Results: At post-intervention, 76.9% of the intervention group and 55.8% of the control group achieved adherence (χ2 = 5.211, P = 0.022, RR = 0.75 (0.55-0.96), Cohen's w = 0.224). Also, median CD4+ cell count of the intervention group increased from 193 cells/ml to 575.0 cells/ml against 131.0 cells/ml to 361.5 cells/ml in the control group (P = 0.007). Conclusion: Adherence counseling and text message reminders improved adherence among HIV patients. Its adoption for HIV patient management is advocated.
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    Mobile phone technology is a novel way of delivering health care and improving health outcomes. This trial investigates the use of motivational mobile phone text messages (SMS) to improve adherence to antiretroviral therapy (ART) over six months. CAMPS was a single-site randomized two-arm parallel design trial in Yaoundé, Cameroon. We enrolled and randomized HIV-positive adults on ART, aged 21 years and above to receive a weekly standardized motivational text message versus usual care alone. The primary outcome was adherence measured using a visual analogue scale (VAS), number of doses missed (in the week preceding the interview) and pharmacy refill data. Outcomes were measured at 3 and 6 months. Service providers and outcome assessors were blinded to allocation. Analysis was by intention-to-treat. Between November and December 2010, 200 participants were randomized, with 101 in the intervention group and 99 in the control group. At 6 months, overall retention was 81.5%. We found no significant effect on adherence by VAS>95% (risk ratio [RR] 1.06, 95% confidence interval [CI] 0.89, 1.29; p = 0.542; reported missed doses (RR 1.01, 95% CI 0.87, 1.16; p>0.999) or number of pharmacy refills (mean difference [MD] 0.1, 95% CI: 0.23, 0.43; p = 0.617. One participant in the intervention arm reported a possible disclosure of status. Standardized motivational mobile phone text messages did not significantly improve adherence to ART in this study. Other types of messaging or longer term studies are recommended. REGISTRATION: 1. Pan-African Clinical Trials Registry; PACTR201011000261458 2. Clinicaltrials.gov; NCT01247181.
  • Article
    OBJECTIVES:: Large unselected studies on representative samples of HIV-infected patients with a whole battery of neuropsychological tests and cerebral MRI scan are required to assess (i) the frequency of neurocognitive impairment (NCI), (ii) the determinants of mild neurocognitive disorders (MND), or HIV-associated dementia (HAD) and (iii) the relationship between NCI and MRI scan findings. METHODS:: Investigation of 400 consecutively enrolled HIV-1 infected adults from the ANRS CO3 Aquitaine Cohort, using standardized neurocognitive tests chosen to achieve consistency with Frascati's criteria. Half of the patients had a cerebral MRI scan allowing gray and white matter volumes measurement. Factors associated with NCI were studied by logistic regression models. RESULTS:: Median age of participants was 47 years, 79% were male and 89% received combination antiretroviral treatment (cART), of whom 93% had plasma HIV RNA <500 copies/mL. Median CD4 count was 515/mm. Prevalence of NCI was 59% including 21% of asymptomatic NCI, 31% of MND, and 7% of HAD. A low level of education, prior neurologic AIDS-defining disorders event, anxiety, depressive symptoms and prior history of brain damage were independent associated with MND or HAD, but neither HIV- nor cART-related variables. The presence of NCI was significantly associated with lower grey matter fraction. INTERPRETATION:: In this large unselected cohort, a high prevalence of symptomatic neurocognitive disorders was mainly related to its traditional determinants and associated with grey matter atrophy at early stages of the disease.
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    Adherence is central to the success of antiretroviral therapy. Supporting adherence has gained importance in HIV care in many national treatment programs. The ubiquity of mobile phones, even in resource-constrained settings, has provided an opportunity to utilize an inexpensive, contextually feasible technology for adherence support in HIV in these settings. We aimed to assess the influence of mobile phone reminders on adherence to antiretroviral therapy in South India. Participant experiences with the intervention were also studied. This is the first report of such an intervention for antiretroviral adherence from India, a country with over 800 million mobile connections.
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    Mobile phones provide a low cost method of addressing certain health system needs in developing countries. We examined SMS-supported interventions for prevention, surveillance, management and treatment compliance of communicable and non-communicable diseases in developing countries. We searched both peer-reviewed and grey literature reporting the use of SMS messages for disease prevention, surveillance, self-management and compliance in developing countries. A total of 98 applications fulfilled the inclusion criteria (33 prevention, 19 surveillance, 29 disease management and 17 patient compliance applications). In 31 projects, the SMS applications were evaluated. The majority of applications focused on HIV/AIDS and were located in India, South Africa and Kenya. Most used bulk (push) messaging. In general, they were well accepted by the population. The review provides further evidence that mobile phones are an appropriate and promising tool for disease control interventions in developing countries.
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    Objective: This study sought to determine if dynamically tailored medication messages delivered to people living with HIV (PLWH) via text messaging would be well received and enhance adherence and clinical outcomes. Methods: A preexperimental proof-of-concept study with 52 men who have sex with men (MSM) recruited from a health clinic focused on promoting the well-being of gay, lesbian, bisexual, and transgender people. Inclusion criteria were being an English speaking HIV-positive MSM, aged 25 or older. Participants also had to agree to allow access to their medical records, have a cell phone, and be able to receive text messages over the 3-month intervention period. Participants completed baseline surveys that assessed various demographic, social, and health questions; received text messages over 3 months; answered weekly adherence questions via two-way messaging; and completed a follow-up survey at the end of the intervention period. Clinical outcomes were abstracted from participants' medical records at baseline and follow-up. Self-reported medication adherence and clinical outcomes, including CD4 counts and viral load. Results: Participants were receptive to the text messaging intervention, and reported reading and liking the messages. Self-reported medication adherence significantly improved among participants who began the study as nonadherent and received tailored medication reminders. Overall viral load significantly decreased and CD4 count significantly increased from baseline to follow-up. Conclusions: The results demonstrate that using two-way text messaging to dynamically tailor adherence messages may enhance adherence and improve important clinical outcomes for PLWH.
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    More than 34 million people are presently living with HIV infection. Antiretroviral therapy (ART) can help these people to live longer, healthier lives, but adherence to ART can be difficult. Mobile phone text-messaging has the potential to help promote adherence in these patients. To determine whether mobile phone text-messaging is efficacious in enhancing adherence to ART in patients with HIV infection. Using the Cochrane Collaboration's validated search strategies for identifying randomised controlled trials and reports of HIV interventions, along with appropriate keywords and MeSH terms, we searched a range of electronic databases, including the Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE, Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS), MEDLINE (via PubMed), PsycINFO, Web of Science, and the World Health Organization (WHO) Global Index Medicus. The date range was from 01 January 1980 to 01 November 2011. There were no limits to language or publication status. Randomised controlled trials (RCTs) in which patients or their caregivers (in the case of infants and children) of any age, in any setting, and receiving ART were provided with mobile phone text messages as a means of promoting adherence to ART. Two authors independently examined the abstracts of all identified trials. We initially identified 243 references. Seventeen full-text articles were closely reviewed. Both authors abstracted data independently, using a pre-designed, standardised data collection form. When appropriate, data were combined in meta-analysis. Two RCTs from Kenya were included in the review. One trial compared short weekly text messages against standard care. The other trial compared short daily, long daily, short weekly and long weekly messages against standard care. Both trials were with adult patients.In the trial comparing only short weekly messages to standard care, text messaging was associated with a lower risk of non-adherence at 12 months (RR 0.77, 95% CI 0.63 to 0.93) and with the non-occurrence of virologic failure at 12 months (RR 0.83, 95% CI 0.69 to 0.99).In the trial that compared different intervals and lengths for text-messaging to standard care, long weekly text-messaging was not significantly associated with a lower risk of non-adherence compared to standard care (RR 0.79, 95% CI 0.60 to 1.04). Patients receiving weekly text-messages of any length were at lower risk of non-adherence at 48 weeks than were patients receiving daily messages of any length (RR 0.79, 95% CI 0.64 to 0.99). There were no significant differences between weekly text-messaging of any length (RR 1.01, 95% CI 0.75 to 1.37) and between short or long messaging at either interval (RR 0.99, 95% CI 0.78 to 1.27). Compared to standard care, any daily text-messaging, whether short or long, did not reduce the risk for non-adherence (RR 0.99, 95% CI 0.82 to 1.20).In meta-analysis of both trials, any weekly text-messaging (i.e. whether short or long messages) was associated with a lower risk of non-adherence at 48-52 weeks (RR 0.78, 95% CI 0.68 to 0.89). The effect of short weekly text-messaging was also significant (RR 0.77, 95% CI 0.67 to 0.89). There is high-quality evidence from the two RCTs that mobile phone text-messaging at weekly intervals is efficacious in enhancing adherence to ART, compared to standard care. There is high quality evidence from one trial that weekly mobile phone text-messaging is efficacious in improving HIV viral load suppression. Policy-makers should consider funding programs proposing to provide weekly mobile phone text-messaging as a means for promoting adherence to antiretroviral therapy. Clinics and hospitals should consider implementing such programs. There is a need for large RCTs of this intervention in adolescent populations, as well as in high-income countries.
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    A growing proportion of patients on antiretroviral therapy in resource-limited settings have switched to second-line regimens. We carried out a systematic review in order to summarize reported rates and reasons for virological failure among people on second-line therapy in resource-limited settings. Two reviewers independently searched four databases and three conference websites. Full text articles were screened and data extracted using a standardized data extraction form. We retrieved 5812 citations, of which 19 studies reporting second-line failure rates in 2035 patients across low-income and middle-income countries were eligible for inclusion. The cumulative pooled proportion of adult patients failing virologically was 21.8, 23.1, 26.7 and 38.0% at 6, 12, 24 and 36 months, respectively. Most studies did not report adequate information to allow discrimination between drug resistance and poor adherence as reasons for virological failure, but for those that did poor adherence appeared to be the main driver of virological failure. Mortality on second-line was low across all time points. Rates of virological failure on second-line therapy are high in resource-limited settings and associated with duration of exposure to previous drug regimens and poor adherence. The main concern appears to be poor adherence, rather than drug resistance, from the limited number of studies accessing both factors. Access to treatment options beyond second-line remains limited and, therefore, a cause for a concern for those patients in whom drug resistance is the identified cause of virological failure.
  • Article
    To assess whether a warning system based on mobile SMS messages increases the adherence of HIV-infected Brazilian women to antiretroviral drug-based treatment regimens and their impressions and satisfaction with respect to incoming messages. A randomized controlled trial was conducted from May 2009 to April 2010 with HIV-infected Brazilian women. All participants (n=21) had a monthly multidisciplinary attendance; each participant was followed over a 4-month period, when adherence measures were obtained. Participants in the intervention group (n=8) received SMS messages 30 min before their last scheduled time for a dose of medicine during the day. The messages were sent every Saturday and Sunday and on alternate days during the working week. Participants in the control group (n=13) did not receive messages. Self-reported adherence, pill counting, microelectronic monitors (MEMS) and an interview about the impressions and satisfaction with respect to incoming messages. The HIV Alert System (HIVAS) was developed over 7 months during 2008 and 2009. After the study period, self-reported adherence indicated that 11 participants (84.62%) remained compliant in the control group (adherence exceeding 95%), whereas all 8 participants in the intervention group (100.00%) remained compliant. In contrast, the counting pills method indicated that the number of compliant participants was 5 (38.46%) for the control group and 4 (50.00%) for the intervention group. Microelectronic monitoring indicated that 6 participants in the control group (46.15%) were adherent during the entire 4-month period compared to 6 participants in the intervention group (75.00%). According to the feedback of the 8 participants who completed the research in the intervention group, along with the feedback of 3 patients who received SMS for less than 4 months, that is, did not complete the study, 9 (81.81%) believed that the SMS messages aided them in treatment adherence, and 10 (90.90%) responded that they would like to continue receiving SMS messages. SMS messaging can help Brazilian women living with HIV/AIDS to adhere to antiretroviral therapy for a period of at least 4 months. In general, the results are encouraging because the SMS messages stimulated more participants in the intervention group to be adherent to their treatment, and the patients were satisfied with the messages received, which were seen as reminders, incentives and signs of affection by the health clinic for a marginalized population.
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    The success of potent antiretroviral treatment for HIV infection is primarily determined by adherence. We systematically review the evidence of effectiveness of interventions to increase adherence to antiretroviral treatment in sub-Saharan Africa. We identified 27 relevant reports from 26 studies of behavioural, cognitive, biological, structural, and combination interventions done between 2003 and 2010. Despite study diversity and limitations, evidence suggests that treatment supporters, directly observed therapy, mobile-phone text messages, diary cards, and food rations can effectively increase adherence in sub-Saharan Africa. However, some interventions are unlikely to have large or lasting effects, and others are effective only in specific settings. These findings emphasise the need for more research, particularly for randomised controlled trials, to examine the effect of context and specific features of intervention content on effectiveness. Future work should assess intervention targeting and selection of interventions based on behavioural theories relevant to sub-Saharan Africa.
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    Antiretroviral drugs have been shown to reduce risk of mother-to-child transmission of human immunodeficiency virus (HIV) and are also widely used for post-exposure prophylaxis for parenteral and sexual exposures. Observational data, ecological studies and models suggest that sexual transmission may be lower in couples in which one partner is infected with HIV and the other is not and the infected partner is on antiretroviral therapy (ART). To determine if ART use in an HIV-infected member of an HIV-discordant couple is associated with lower risk of HIV transmission to the uninfected partner compared to untreated discordant couples. We used standard Cochrane methods to search electronic databases and conference proceedings with relevant search terms without limits to language. Randomised controlled trials, cohort studies and case-control studies of HIV-discordant couples in which the HIV-infected member of the couple was being treated or not treated with ART DATA COLLECTION AND ANALYSIS: Abstracts of all trials identified by electronic or bibliographic scanning were examined independently by two authors. We initially identified 1814 references and examined 24 in detail for study eligibility. Data were abstracted independently using a standardised abstraction form. One randomised controlled trial and seven observational studies were included in the review. These eight studies identified 464 episodes of HIV transmission, 72 among treated couples and 392 among untreated couples. The rate ratio for the single randomised controlled trial was 0.04 [95% CI 0.00, 0.27]. All index partners in this study had CD4 cell counts at baseline of 350-550 cells/µL. Similarly, the summary rate ratio for the seven observational studies was 0.34 [95% CI 0.13, 0.92], with substantial heterogeneity (I(2)=73%). After excluding two studies with inadequate person-time data, we estimated a summary rate ratio of 0.16 [95% CI 0.07, 0.35] with no noted heterogeneity (I(2)=0%). We also performed subgroup analyses among the observational studies to see if the effect of ART on prevention of HIV differed by the index partner's CD4 cell count. Among couples in which the infected partner had ≥350 CD4 cells/µL, we estimated a rate ratio of 0.02 [95% CI 0.00, 2.87]. In this subgroup, there were 61 transmissions in untreated couples and none in treated couples. ART is a potent intervention for prevention of HIV in discordant couples in which the index partner has ≤550 CD4 cells/µL. A new multicentre randomised controlled trial confirms the suspected benefit seen in earlier observational studies. Questions remain about durability of protection, the balance of benefits and adverse events associated with earlier therapy, long-term adherence and transmission of ART-resistant strains to partners. Resource limitations and implementation challenges must also be addressed.Counselling, support, and follow up, as well as mutual disclosure, may have a role in supporting adherence, so programmes should be designed with these components. In addition to ART provision, the operational aspects of delivering such programmes must be considered.
  • Article
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    Adherence to antiretroviral therapy (ART) represents one of the strongest predictors of progression to AIDS, yet it is difficult for most patients to sustain high levels of adherence. This study compares the efficacy of a personalized cell phone reminder system (ARemind) in enhancing adherence to ART versus a beeper. Twenty-three HIV-infected subjects on ART with self-reported adherence less than 85% were randomized to a cellular phone (CP) or beeper (BP). CP subjects received personalized text messages daily; in contrast, BP subjects received a reminder beep at the time of dosing. Interviews were scheduled at weeks 3 and 6. Adherence to ART was measured by self-report (SR, 7-day recall), pill count (PC, past 30 days at baseline, then past 3 weeks), Medication Event Monitoring System (MEMS; cumulatively at 3 and 6 weeks), and via a composite adherence score constructed by combining MEMS, pill count, and self report. A mixed effects model adjusting for baseline adherence was used to compare adherence rates between the intervention groups at 3 and 6 weeks. Nineteen subjects completed all visits, 10 men and 9 females. The mean age was 42.7 ± 6.5 years, 37% of subjects were Caucasian and 89% acquired HIV heterosexually. The average adherence to ART was 79% by SR and 65% by PC at baseline in both arms; over 6 weeks adherence increased and remained significantly higher in the ARemind group using multiple measures of adherence. A larger and longer prospective study is needed to confirm these findings and to better understand optimal reminder messages and user fatigue.
  • Article
    There is limited evidence on whether growing mobile phone availability in sub-Saharan Africa can be used to promote high adherence to antiretroviral therapy (ART). This study tested the efficacy of short message service (SMS) reminders on adherence to ART among patients attending a rural clinic in Kenya. A randomized controlled trial of four SMS reminder interventions with 48 weeks of follow-up. Four hundred and thirty-one adult patients who had initiated ART within 3 months were enrolled and randomly assigned to a control group or one of the four intervention groups. Participants in the intervention groups received SMS reminders that were either short or long and sent at a daily or weekly frequency. Adherence was measured using the medication event monitoring system. The primary outcome was whether adherence exceeded 90% during each 12-week period of analysis and the 48-week study period. The secondary outcome was whether there were treatment interruptions lasting at least 48 h. In intention-to-treat analysis, 53% of participants receiving weekly SMS reminders achieved adherence of at least 90% during the 48 weeks of the study, compared with 40% of participants in the control group (P = 0.03). Participants in groups receiving weekly reminders were also significantly less likely to experience treatment interruptions exceeding 48 h during the 48-week follow-up period than participants in the control group (81 vs. 90%, P = 0.03). These results suggest that SMS reminders may be an important tool to achieve optimal treatment response in resource-limited settings.
  • Article
    Mobile (cell) phone communication has been suggested as a method to improve delivery of health services. However, data on the effects of mobile health technology on patient outcomes in resource-limited settings are limited. We aimed to assess whether mobile phone communication between health-care workers and patients starting antiretroviral therapy in Kenya improved drug adherence and suppression of plasma HIV-1 RNA load. WelTel Kenya1 was a multisite randomised clinical trial of HIV-infected adults initiating antiretroviral therapy (ART) in three clinics in Kenya. Patients were randomised (1:1) by simple randomisation with a random number generating program to a mobile phone short message service (SMS) intervention or standard care. Patients in the intervention group received weekly SMS messages from a clinic nurse and were required to respond within 48 h. Randomisation, laboratory assays, and analyses were done by investigators masked to treatment allocation; however, study participants and clinic staff were not masked to treatment. Primary outcomes were self-reported ART adherence (>95% of prescribed doses in the past 30 days at both 6 and 12 month follow-up visits) and plasma HIV-1 viral RNA load suppression (<400 copies per mL) at 12 months. The primary analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, NCT00830622. Between May, 2007, and October, 2008, we randomly assigned 538 participants to the SMS intervention (n=273) or to standard care (n=265). Adherence to ART was reported in 168 of 273 patients receiving the SMS intervention compared with 132 of 265 in the control group (relative risk [RR] for non-adherence 0·81, 95% CI 0·69-0·94; p=0·006). Suppressed viral loads were reported in 156 of 273 patients in the SMS group and 128 of 265 in the control group, (RR for virologic failure 0·84, 95% CI 0·71-0·99; p=0·04). The number needed to treat (NNT) to achieve greater than 95% adherence was nine (95% CI 5·0-29·5) and the NNT to achieve viral load suppression was 11 (5·8-227·3). Patients who received SMS support had significantly improved ART adherence and rates of viral suppression compared with the control individuals. Mobile phones might be effective tools to improve patient outcome in resource-limited settings. US President's Emergency Plan for AIDS Relief.
  • Article
    To correlate self-reported antiretroviral adherence with virologic suppression. Prospective observational study of adherence to therapy nested in a randomized comparative trial of frequent versus infrequent monitoring of plasma HIV RNA. Five university-affiliated HIV clinics. A group of 173 HIV-infected patients with a mean baseline CD4 count of 142 x 10(6) cells/l (range 3-515) of whom 164 and 119 completed adherence questionnaires at 2 and 6 months, respectively. Individualized, unrestricted antiretroviral therapy. Patients were classified into four groups by adherence to therapy in the previous 4 weeks (< 80%, 80-95%, 95-99%, 100%). Plasma HIV RNA levels and CD4 lymphocyte counts were measured bimonthly. Recreational drug or alcohol use was associated with decreased adherence, whereas frequency of HIV RNA monitoring, demographic variables, (age, gender, education, and risk group) and stage of disease had no effect. Greater HIV suppression at 6 months was seen across four categories of increasing adherence (P = 0.009 for linear trend). Patients reporting < 80% adherence at 6 months had a 0.2 log10 copies/ml increase in HIV RNA and a loss of 19 x 10(6) CD4 cells/l compared with a 1.1 log10 copies/ml decrease in HIV RNA and an increase of 72 x 10(6) CD4 cells/l in those reporting 100% adherence (P = 0.02). Self-reported poor adherence (< 80%) and drug or alcohol use predicted non-response of HIV RNA at 6 months of antiretroviral therapy.