Improving ART adherence: what works?

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

Kanters S, Park JJ, Chan K, Socias ME, Ford N, Forrest JI, Thorlund K, Nachega JB, Mills EJ. Lancet HIV. 2017 Jan;4(1):e31-e40. doi: 10.1016/S2352-3018(16)30206-5. Epub 2016 Nov 16.

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 For the global network, the time discrepancy (whether the study outcome was measured during or after intervention was withdrawn) was an effect modifier for both adherence to antiretroviral therapy (coefficient estimate -0.43, 95% CrI -0.75 to -0.11) and viral suppression (-0.48; -0.84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.

Abstract access   [1]

Editor’s notes: Maintaining adherence to self-administered medications is difficult. On average, people who are prescribed medications for chronic diseases take fewer than half the prescribed doses. Evidence suggests that in most settings adherence to antiretroviral therapy (ART) is better than this, but there will always be people that struggle to maintain the high levels of adherence required for durable virologic suppression. In this analysis, there was some evidence that specific activities or combinations of activities improved virologic suppression. However, the effect sizes were small and when the analysis was confined to studies in low-income and middle-income countries, there was no evidence to suggest an effect on virologic suppression. Overall the evidence to support any particular activity or combination of activities was not compelling.     

Findings from this analysis have been incorporated into most recent consolidated ART guidelines from the World Health Organization. Trying to summarize complex evidence in this way creates many challenges. Trials were conducted in different populations. Some with all people starting ART, others with people considered to have high risk of suboptimal adherence, and others with people who already had adherence problems. The trials also naturally would have differed in content and quality of the usual package of care to support adherence (the comparator for most programme). 60% of the trials were conducted exclusively in the United States, while others were conducted across different settings.

These are just some of the things that make it difficult to synthesize this evidence into guidance that can be applicable to people living with HIV worldwide. HIV programmes in countries have to decide whether or not to adopt any of these activities that are recommended by WHO on the basis of relatively weak evidence. Would we expect activities aimed at improving adherence to be generalizable across different settings? One might argue probably not. Adherence is a multifactorial, dynamic process and there is unlikely to be a ‘one size fits all’ approach to supporting adherence. In the absence of better evidence for any specific activity, we should perhaps focus on improving the quality of the basic package of adherence support offered to all people receiving ART, while also developing better ways to identify when certain people might benefit from enhanced support.        

Health care delivery [3], HIV Treatment [4]
Africa [5], Asia [6], Europe [7], Latin America [8], Northern America [9]
Brazil [10], Cameroon [11], China [12], France [13], Kenya [14], Mozambique [15], Nigeria [16], South Africa [17], Spain [18], Uganda [19], United Republic of Tanzania [20], United States of America [21]
  • [22]