Adherence to first-line antiretroviral therapy affects non-virologic outcomes among patients on treatment for more than 12 months in Lusaka, Zambia

Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.
International Journal of Epidemiology (Impact Factor: 9.18). 02/2009; 38(3):746-56. DOI: 10.1093/ije/dyp004
Source: PubMed


High-level adherence to antiretroviral therapy (ART) is associated with favourable patient outcomes. In resource-constrained settings, however, there are few validated measures. We examined the correlation between clinical outcomes and the medication possession ratio (MPR), a pharmacy-based measure of adherence.
We analysed data from a large programmatic cohort across 18 primary care centres providing ART in Lusaka, Zambia. Patients were stratified into three categories based on MPR-calculated adherence over the first 12 months: optimal (> or =95%), suboptimal (80-94%) and poor (<80%).
Overall, 27 115 treatment-naïve adults initiated and continued ART for > or =12 months: 17 060 (62.9%) demonstrated optimal adherence, 7682 (28.3%) had suboptimal adherence and 2373 (8.8%) had poor adherence. When compared with those with optimal adherence, post-12-month mortality risk was similar among patients with sub-optimal adherence [adjusted hazard ratio (AHR) = 1.0; 95% CI: 0.9-1.2] but higher in patients with poor adherence (AHR = 1.7; 95% CI: 1.4-2.2). Those <80% MPR also appeared to have an attenuated CD4 response at 18 months (185 cells/microl vs 217 cells/microl; P < 0.001), 24 months (213 cells/microl vs 246 cells/microl; P < 0.001), 30 months (226 cells/microl vs 261 cells/microl; P < 0.001) and 36 months (245 cells/microl vs 275 cells/microl; P < 0.01) when compared with those above this threshold.
MPR was predictive of clinical outcomes and immunologic response in this large public sector antiretroviral treatment program. This marker may have a role in guiding programmatic monitoring and clinical care in resource-constrained settings.

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Available from: Stewart E Reid
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    • "Several studies have assessed the impact of adherence on mortality and report evidence of an association between adherence and long-term mortality risk among HIV infected individuals receiving ART. For example, Chi et al reported a 1.7 fold increased risk of post 12 month mortality in a large scale public sector HIV care programme in Zambia in those with <80% drug possession ratio (DPR) based on pharmacy refill [16]. Lima et al[17] demonstrated a 3 fold increased risk of mortality for a DPR adherence threshold of <95%; Nachega et al[25] reported a 3 fold increased risk of mortality in a South African private sector HIV care programme for pharmacy claims adherence <80%. "
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    ABSTRACT: Adherence is one of the most important determinants of viral suppression and drug resistance in HIV- infected people receiving antiretroviral therapy (ART). We examined the association between long-term mortality and poor adherence to ART in DART trial participants in Uganda and Zimbabwe randomly assigned to receive laboratory and clinical monitor- ing (LCM), or clinically driven monitoring (CDM). Since over 50% of all deaths in the DART trial occurred during the first year on ART, we focussed on participants continuing ART for 12 months to investigate the implications of longer-term adherence to treatment on mortality. Participants' ART adherence was assessed by pill counts and structured questionnaires at 4-weekly clinic visits. We studied the effect of recent adherence history on the risk of death at the individual level (odds ra- tios from dynamic logistic regression model), and on mortality at the population level (population attributable fraction based on this model). Analyses were conducted separately for both randomiza- tion groups, adjusted for relevant confounding factors. Adherence behaviour was also confounded by a partial factorial randomization comparing structured treatment interruptions (STI) with continuous ART (CT). In the CDM arm a significant association was found between poor adherence to ART in the previous 3-9 months with increased mortality risk. In the LCM arm the association was not significant. The odds ratios for mortality in participants with poor adherence against those with optimal adherence was 1.30 (95% CI 0.78,2.10) in the LCM arm and 2.18 (1.47,3.22) in the CDM arm. The estimated proportions of deaths that could have been avoided with optimal adherence (population attributable fraction) in the LCM and CDM groups during the 5 years follow-up period were 16.0% (95% CI 0.7%,31.6%) and 33.1% (20.5%,44.8%), correspondingly. Recurrent poor adherence determined even through simple measures is associated with high mortality both at individual level as well as at the ART programme level. The number of lives saved through effective interventions to improve adherence could be considerable particularly for individuals mon- itored without using CD4 cell counts. The findings have important implications for clinical practice and for developing interventions to enhance adherence.
    Full-text · Article · Aug 2013 · BMC Infectious Diseases
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    • "The development of HIV drug resistant strains is a concern in situations where treatment is started at higher CD4 count thresholds, as in the case of ART as prevention, since people will be on HIV treatment for longer with increased potential for of sub-optimal adherence. Some studies have shown that adherence is lower in individuals starting ART at higher CD4 counts [44,45]. However, limited available data do not suggest an increased risk of drug resistance with earlier HIV treatment [46]. "
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    ABSTRACT: Antiretroviral therapy (ART) suppresses HIV viral load in all body compartments and so limits the risk of HIV transmission. It has been suggested that ART not only contributes to preventing transmission at individual but potentially also at population level. This trial aims to evaluate the effect of ART initiated immediately after identification/diagnosis of HIV-infected individuals, regardless of CD4 count, on HIV incidence in the surrounding population. The primary outcome of the overall trial will be HIV incidence over two years. Secondary outcomes will include i) socio-behavioural outcomes (acceptability of repeat HIV counselling and testing, treatment acceptance and linkage to care, sexual partnerships and quality of life); ii) clinical outcomes (mortality and morbidity, retention into care, adherence to ART, virologic failure and acquired HIV drug resistance), iii) cost-effectiveness of the intervention. The first phase will specifically focus on the trial's secondary outcomes.Methods/design: A cluster-randomised trial in 34 (2 x 17) clusters within a rural area of northern KwaZulu-Natal (South Africa), covering a total population of 34,000 inhabitants aged 16 years and above, of whom an estimated 27,200 would be HIV-uninfected at start of the trial. The first phase of the trial will include ten (2 x 5) clusters. Consecutive rounds of home-based HIV testing will be carried out. HIV-infected participants will be followed in nearby dedicated trial clinics: in intervention clusters, they will be offered immediate ART initiation regardless of CD4 count and clinical stage; in control clusters they will be offered ART according to national treatment eligibility guidelines (CD4 <350 cells/muL, World Health Organisation stage 3 or 4 disease or multidrug-resistant/extensively drug-resistant tuberculosis). Following proof of acceptability and feasibility from the first phase, the trial will be rolled out to further clusters. We aim to provide proof-of-principle evidence regarding the effectiveness of Treatment-as-Prevention in reducing HIV incidence at the population level. Data collected from the participants at home and in the clinics will inform understanding of socio-behavioural, economic and clinical impacts of the intervention as well as feasibility and generalizability.Trial registration: NCT01509508; South African Trial Register: DOH-27-0512-3974.
    Full-text · Article · Jul 2013 · Trials
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    • "While achievements have been remarkable, the universal coverage and retaining the patients on ART remain as challenges. Studies showed that 59.5% of patients in Zambia’s southern province throughout a period of 15–723 days (a median follow-up of 275 days) and 62.9% of patients in Lusaka over the first 12 months (a median follow-up of 15.7 months from 12 months onwards) were adherent to ART[11,12]. "
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    ABSTRACT: Background Around 70% of those living with HIV in need of treatment accessed antiretroviral therapy (ART) in Zambia by 2009. However, sustaining high levels of adherence to ART is a challenge. This study aimed to identify the predictive factors associated with ART adherence during the early months of treatment in rural Zambia. Methods This is a field based observational longitudinal study in Mumbwa district, which is located 150 km west of Lusaka, the capital of Zambia. Treatment naive patients aged over 15 years, who initiated treatment during September-November 2010, were enrolled. Patients were interviewed at the initiation and six weeks later. The treatment adherence was measured according to self-reporting by the patients. Multiple logistic regression analysis was performed to identify the predictive factors associated with the adherence. Results Of 157 patients, 59.9% were fully adherent to the treatment six weeks after starting ART. According to the multivariable analysis, full adherence was associated with being female [Adjusted Odds Ratio (AOR), 3.3; 95% Confidence interval (CI), 1.2-8.9], having a spouse who were also on ART (AOR, 4.4; 95% CI, 1.5-13.1), and experience of food insufficiency in the previous 30 days (AOR, 5.0; 95% CI, 1.8-13.8). Some of the most common reasons for missed doses were long distance to health facilities (n = 21, 53.8%), food insufficiency (n = 20, 51.3%), and being busy with other activities such as work (n = 15, 38.5%). Conclusions The treatment adherence continues to be a significant challenge in rural Zambia. Social supports from spouses and people on ART could facilitate their treatment adherence. This is likely to require attention by ART services in the future, focusing on different social influences on male and female in rural Zambia. In addition, poverty reduction strategies may help to reinforce adherence to ART and could mitigate the influence of HIV infection for poor patients and those who fall into poverty after starting ART.
    Full-text · Article · Dec 2012 · Annals of Clinical Microbiology and Antimicrobials
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