Postpartum Adherence Clubs for Antiretroviral Therapy: a randomised controlled trial

Over the past 20 years there have been major advances in preventing the mother-to-child-transmission (PMTCT) of HIV, and interventions based on this knowledge have resulted in transmission rates <1% in the United Kingdom and Europe, attributable largely to widespread use of combination antiretroviral therapy (ART) in pregnancy. The remarkable effectiveness of these interventions has led many to suggest that the global elimination of paediatric HIV infection may be possible. Towards this, there is particular excitement regarding universal initiation of lifelong ART for all HIV-infected pregnant women following the World Health Organisation's "Option B+" approach, and this strategy has been implemented in many parts of Africa, including the Western Cape Province of South Africa (SA) from July 2013. But despite considerable optimism, more than 300 000 new paediatric HIV infections occur each year around the globe; almost 10% of these are in SA alone. In turn there is growing recognition that the "Option B+" approach must be accompanied by effective and efficient models of care for delivering ART to unprecedented numbers of HIV-infected pregnant women.

For women starting lifelong ART in pregnancy, there is particular concern about the postpartum period (for the purposes of this proposal, this is from delivery until 24 months postpartum) as a time when HIV-infected women are at a very high risk of not taking their medications (non-adherence) and/or dropping out of care altogether (non-retention). Over the last few years there has been growing evidence that the postpartum period is a difficult time for women on ART, but there are few interventions that aim to support HIV-infected women during this time. One of the few interventions for this purpose is the 'Adherence Club' model. In South Africa and most parts of Africa, HIV-infected patients (including pregnant and postpartum women) attend primary care clinics where doctors and nurses focus on the clinical care of individual patients. In contrast to this, the Adherence Club model is operated by community health workers (lay people without clinical training) working from community venues that are located closer to peoples' homes. There is preliminary evidence that the Adherence Club model could lead to better clinical outcomes than standard clinical services, but the observational studies used to generate this evidence have significant methodological flaws.

To help generate robust evidence about the Adherence Club model for managing HIV-infected women on ART during the postpartum period, we plan to enroll 388 HIV-infected pregnant women on ART immediately after delivery. These women will be allocated at random to either attend routine primary health care clinics for their ART during the postpartum period, or to attend an Adherence Club. Women will be followed up by a study measurement team (that operates separately from either of the clinical services) at regular intervals through 24 months postpartum. This measurement team will check the HIV viral loads and administer questionnaires to women who are participating. The primary focus of the study is the retention of women in care, and their adherence to ART, during the 24-month period. There are secondary outcomes related to the acceptability of the Adherence Club model, and also the cost-effectiveness of the model, compared to standard primary care services as the control condition.

Recently, major changes to international policy have called for the provision of lifelong antiretroviral therapy (ART) to all HIV-infected pregnant women regardless of CD4 cell count or HIV disease stage (WHO's "Option B+" approach). However there are significant concerns around ART adherence and retention in care in postpartum women, and there is an urgent need for evidence-based models of service delivery for "Option B+". Adherence Clubs (ACs) are an innovative but untested method to support women who initiate ART in pregnancy. Preliminary data suggest that the AC approach may lead to outcomes that are at least comparable to those achieved by services delivered through doctor-driven, routine primary care clinics, but high quality data are lacking.

We propose a randomised controlled trial to examine the impact of postpartum adherence clubs on maternal and child health outcomes in Cape Town, South Africa. The trial will randomise 388 HIV-infected women and their HIV-exposed infants within 7 days postpartum to either (a) referral to ART services at local adult ART clinics, following the current standard of care, or (b) referral to a community-based ART adherence club. The primary outcome is the combined endpoint of maternal retention in care (alive and attending ART services) and viral suppression up to 24 months postpartum. Secondary outcomes are: the individual components of the composite primary outcome; measures of health and health care service utilization in HIV-infected women and the HIV-exposed children of participating mothers (including HIV DNA PCR testing for vertical HIV transmission and infant immunizations received); acceptability of the AC model of care, compared to the standard of care; and the costs and cost-effectiveness of the AC intervention compared to the standard of care.

Who will benefit from this research?

The proposed research will benefit mainly health care policymakers in low- and middle-income countries where HIV is prevalent, particular in South and southern Africa, as well as HIV-infected women and their HIV-exposed infants in these settings. Across sub-Saharan Africa, there is increasing emphasis on the universal initiation of lifelong antiretroviral therapy (ART) in all HIV-infected pregnant women, following 2013 recommendations from the World Health Organisation. However there is emerging scientific evidence indicating that levels of adherence to ART, and retention in ART services, are problematic during the postpartum period. There are few interventions to promote ART services in the postpartum period, and the evidence base for existing approaches is thin. In turn, there is an urgent need for new interventions that can be used to support adherence and retention among HIV-infected women on ART during the postpartum period.

'Adherence Clubs' (a community-based model of care for the management of stable ART patients) is one potential intervention that may be used to support postpartum HIV-infected women and their infants. There is observational evidence suggesting that 'Adherence Clubs' to manage HIV-infected individuals on ART leads to clinical outcomes that are comparable to those achieved by traditional primary health care services. However this evidence is prone to severe selection biases. The research proposes a rigorous evaluation of the Adherence Club model of care to facilitate postpartum retention in care and adherence to ART for HIV-infected women.

How will they benefit from this research?

This research will benefit health care policymakers by strengthening the evidence base for postpartum adherence and retention of HIV-infected women on ART. Of critical importance is the proposed research's inclusion of a range of trial measures that encompass clinical outcomes, patient acceptability and cost-effectiveness. While clinical outcomes (retention in ART services and adherence to therapy, as reflected by HIV viral load measures) are the primary focus of the trial, secondary outcomes on acceptability are valuable for understanding the feasibility of the clubs model, as well as the patient subgroups in whom the intervention may be more or less effective. In addition, cost-effectiveness outcomes are an important part of the potential policy benefit of this work: the 'Adherence Club' model is operated by community health workers and widely thought to be less costly than more clinically-intensive primary care services, but the cost-benefit ratios remain poorly understood.

The research will benefit HIV-infected women initiating ART in South Africa and other parts of the continent by evaluating a model of care that may be more effective and more acceptable than standard facility-based health services for long-term ART adherence. The inclusion of patient acceptability indicators is an important component towards this end.