Interventions to promote adherence to antiretroviral therapy in Africa: a network meta-analysis

Summary

Background

Adherence to antiretroviral therapy (ART) is necessary for the improvement of the health of patients and for public health. We sought to determine the comparative effectiveness of different interventions for improving ART adherence in HIV-infected people living in Africa.

Methods

We searched for randomised trials of interventions to promote antiretroviral adherence within adults in Africa. We searched AMED, CINAHL, Embase, Medline (via PubMed), and ClinicalTrials.gov from inception to Oct 31, 2014, with the terms “HIV”, “ART”, “adherence”, and “Africa”. We created a network of the interventions by pooling the published and individual patients' data for comparable treatments and comparing them across the individual interventions with Bayesian network meta-analyses. The primary outcome was adherence defined as the proportion of patients meeting trial defined criteria; the secondary endpoint was viral suppression.

Findings

We obtained data for 14 randomised controlled trials, with 7110 patients. Interventions included daily and weekly short message service (SMS; text message) messaging, calendars, peer supporters, alarms, counselling, and basic and enhanced standard of care (SOC). Compared with SOC, we found distinguishable improvement in self-reported adherence with enhanced SOC (odds ratio [OR] 1·46, 95% credibility interval [CrI] 1·06–1·98), weekly SMS messages (1·65, 1·25–2·18), counselling and SMS combined (2·07, 1·22–3·53), and treatment supporters (1·83, 1·36–2·45). We found no compelling evidence for the remaining interventions. Results were similar when using viral suppression as an outcome, although the network contained less evidence than that for adherence. Treatment supporters with enhanced SOC (1·46, 1·09–1·97) and weekly SMS messages (1·55, 1·01–2·38) were significantly better than basic SOC.

Interpretation

Several recommendations for improving adherence are unsupported by the available evidence. These findings can inform future intervention choices for improving ART adherence in low-income settings.

Funding

None.

Introduction

Antiretroviral therapy (ART) has clinical and public health benefits by decreasing HIV morbidity and mortality and transmission to sex partners.¹ Many patients experience difficulties in taking ART at some time and may take it only sporadically or take drug holidays.² There are many possible reasons for not taking ART, including social, personal, and structural factors.3, 4 Promotion of adherence to ART is one of the chief public health concerns for populations living with HIV.⁵

Despite the importance of achieving and maintaining high rates of ART adherence, few interventions have proved successful among those experiencing difficulties.6, 7 In Africa, where most people with HIV infection live, specific social, structural, or health-system-related barriers exist including food insecurity, stigma, supply-chain interruptions, and a lack of human health resources.⁸ Previous systematic reviews have identified potentially effective interventions, but have not assessed their effectiveness with statistical measures.7, 9, 10

The past decade has seen important progress in evidence synthesis, particularly with the popularisation of network meta-analysis.11, 12, 13, 14 In traditional meta-analysis, all included studies compare the same intervention with the same comparator. Network meta-analysis extends this concept by including multiple pairwise comparisons across a range of interventions and provides estimates of relative treatment effects on multiple comparisons for comparative effectiveness purposes on the basis of direct or indirect evidence. Direct evidence for the effect of treatment B compared with A would correspond to the evidence familiar to us in pairwise meta-analysis, combining all head-to-head comparisons. Indirect evidence corresponds to all comparisons of B and A through common comparators, such as standard of care. Thus, network meta-analysis allows for inference between two interventions even in the absence of head-to-head evidence. The conditions required for these analyses resemble those of traditional meta-analysis; although they require that direct and indirect evidence be in agreement, a condition called consistency. Therefore, we aimed to investigate what ART adherence interventions have been used in the African setting. We used a network meta-analysis approach to draw from both direct and indirect evidence from randomised trials.