Elsevier

The Lancet HIV

Volume 4, Issue 1, January 2017, Pages e31-e40
The Lancet HIV

Articles
Interventions to improve adherence to antiretroviral therapy: a systematic review and network meta-analysis

https://doi.org/10.1016/S2352-3018(16)30206-5Get rights and content

Summary

Background

High adherence to antiretroviral therapy is crucial to the success of HIV treatment. We evaluated comparative effectiveness of adherence interventions with the aim of informing the WHO's global guidance on interventions to increase adherence.

Methods

For this systematic review and network meta-analysis, we searched for randomised controlled trials of interventions that aimed to improve adherence to antiretroviral therapy regimens in populations with HIV. We searched Cochrane Central Register of Controlled Trials, Embase, and MEDLINE for reports published up to July 16, 2015, and searched major conference abstracts from Jan 1, 2013, to July 16, 2015. We extracted data from eligible studies for study characteristics, interventions, patients' characteristics at baseline, and outcomes for the study populations of interest. We used network meta-analyses to compare adherence and viral suppression for all study settings (global network) and for studies in low-income and middle-income countries only (LMIC network).

Findings

We obtained data from 85 trials with 16 271 participants. Short message service (SMS; text message) interventions were superior to standard of care in improving adherence in both the global network (odds ratio [OR] 1·48, 95% credible interval [CrI] 1·00−2·16) and in the LMIC network (1·49, 1·04−2·09). Multiple interventions showed generally superior adherence to single interventions, indicating additive effects. For viral suppression, only cognitive behavioural therapy (1·46, 1·05−2·12) and supporter interventions (1·28, 1·01−1·71) were superior to standard of care in the global network; none of the interventions improved viral response in the LMIC network. For the global network, the time discrepancy (whether the study outcome was measured during or after intervention was withdrawn) was an effect modifier for both adherence to antiretroviral therapy (coefficient estimate −0·43, 95% CrI −0·75 to −0·11) and viral suppression (−0·48; −0·84 to −0·12), suggesting that the effects of interventions wane over time.

Interpretation

Several interventions can improve adherence and viral suppression; generally, their estimated effects were modest and waned over time.

Funding

WHO.

Introduction

The recent scale-up of programmes for antiretroviral therapy has resulted in more than 17 million people receiving treatment worldwide, with most living in low-income and middle-income countries (LMICs).1 Achievement of the optimum clinical, public health, and social outcomes requires early diagnosis, timely linkage and initiation of antiretroviral therapy, and consistent long-term adherence to antiretroviral therapy.2, 3 Few interventions consistently improve adherence.4 Interventions vary in their intensity and approach and have heterogeneous clinical trial results, making interpretation of their effects challenging. For instance, the use of text messaging (ie, short message service [SMS]) to maintain adherence in low-income settings has been widely promoted; however, not all randomised trials have shown clear improvements.5

Over the past two decades important progress has been made in meta-analysis and comparative effectiveness, namely, the development of network meta-analysis.6, 7 Randomised controlled trials, the gold standard of scientific evidence, tend to use control groups of little clinical interest (eg, an older treatment or placebo). As such, determining the comparative effectiveness of two treatments can be difficult because of the absence of head-to-head evidence. Network meta-analyses allow for the comparison of interventions that have not been compared directly.8 Moreover, network meta-analyses simultaneously evaluate all treatment options within a clinical area and so facilitate the evaluation of the complete interventional landscape. As such, these methods naturally lend themselves to the process of evidence synthesis for the purpose of clinical guidelines.

Low adherence has been reported in both high-income countries and LMICs.9 Previous work to assess adherence interventions for antiretroviral therapy has been limited to Africa in the case of network meta-analyses4, 10 and to pairwise comparisons with respect to other reviews.11 Identification of effective interventions is needed for guidance relevant to both high-income countries and LMICs. To inform the latest iteration of the WHO global consolidated guidelines on HIV, we used a network meta-analysis approach,12 aiming to establish the effectiveness of interventions on adherence and, when reported, achievement of viral suppression.

Research in context

Evidence before this study

The 2013 WHO consolidated guidelines on the use of antiretroviral therapy for the treatment and prevention of HIV infection promoted the use of text messaging to improve adherence to therapy. Before we did our systematic literature search, we searched MEDLINE and Embase to find systematic reviews published up to June 1, 2016, that assessed the full spectrum of interventions to improve adherence, using the search string “(HIV or antiretroviral therapy) AND (adherence) AND (systematic review or meta-analysis)”. Previous systematic reviews have been restricted to pairs of interventions; the only network meta-analysis that explored adherence interventions for antiretroviral therapy was limited to studies in Africa. Low rates of adherence have been reported too in high-income settings, so there is a need to explore the evidence at the global setting.

Added value of this study

This was the first network meta-analysis to consider all adherence interventions within a single global analysis. We show that adherence interventions have small effects and that they are not easily statistically distinguishable from one another. These results support the benefits of text messaging, counselling, and supporters, and they further support the additive effect of behavioural and cognitive interventions. Novel to this study, time of outcome measurement with respect to the intervention (ie, whether adherence was assessed while the intervention was still active rather than previously completed) was an effect modifier, suggesting that the effects of interventions wane over time.

Implications to all available evidence

With the recent scale-up of antiretroviral therapy programmes and increasing number of people living with HIV, steps to improve and maintain consistent long-term adherence to antiretroviral therapy are crucial. WHO's recent guidelines used the findings of this comprehensive network meta-analyses, and HIV programmes could consider adopting or adapting these interventions according to resource availability and programme outcomes.

Section snippets

Search strategy and selection criteria

We used the PRISMA extension to network meta-analysis to design and report the trial13 and the protocol for this study is available from the authors on request. We searched the Cochrane Central Register of Controlled Trials, Embase, and MEDLINE for English-language reports published up to July 16, 2015 (search terms in appendix pp 3–4). Interventions targeting enhanced adherence to antiretroviral therapy only (ie, not an antiretroviral therapy regimen) were not eligible. As such, most studies

Results

85 trials met the inclusion criteria (figure 1, appendix pp 26–63),18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102 including all trials in our previous smaller network meta-analysis.10 Trials were of

Discussion

Supportive strategies, including peer support, two-way text messaging, and counselling, and behavioural strategies, such as training, improve adherence compared with standard adherence support. In general, the effects of even the most effective interventions were slight, and might wane after the intervention is withdrawn, although adherence seemed to increase when effective interventions were combined. In many settings, particularly in LMICs, programmes already include treatment supporters via

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