for improving adherence and how this is aﬀected by context. However, when the focus is on lifelong adherence, including continued programme participation, randomised controlled trials would have to last for a very long time and to examine the modulation of eﬀect by context, many trials of diﬀerent interventions in diﬀering contexts would be required. The design and implementation of ART programmes is best supported by reports of long-term programme implementation and eﬀectiveness that also describe and review the role of context and that are assessed using an adequacy or plausibility design.4 Programmes that achieve high retention rates and good longterm adherence can serve as models for other programmes in a similar context. We declare that we have no conﬂicts of interest.
*Saskia de Pee, Nils Grede, Maureen Forsythe, Martin W Bloem [email protected]
Nutrition and HIV/AIDS Policy, Policy and Strategy Division, World Food Programme, Rome 00148, Italy 1
Bärnighausen T, Chaiyachati K, Chimbindi N, Peoples A, Haberer J, Newell M-L. Interventions to increase antiretroviral adherence in sub-Saharan Africa: a systematic review of evaluation studies. Lancet Infect Dis 2011; 11: 942–51. Rosen S, Fox MP, Gill CJ. Patient retention in antiretroviral therapy prorams in Sub-Saharan Africa: a systematic review. PLoS Med 2007; 4: 1691–701. Unge C, Södergård B, Marrone G, et al. Long-term adherence to antiretroviral treatment and program drop-out in a high-risk urban setting in sub-Saharan Africa: a prospective cohort study. PLoS Med 2010; 5: 1–12. Habicht JP, Victora CG, Vaughan JP. Evaluation designs for adequacy, plausibility and probability of public health programme performance and impact. Int J Epidemiol 1999; 28: 10–18.
Authors’ reply We thank Saskia de Pee and colleagues for their thoughtful comments on our systematic review of interventions to increase adherence to antiretroviral treatment (ART) in sub-Saharan Africa.1 We agree that lifelong retention is necessary for treatment adherence and success. 662
Existing evidence for retention within ART programmes does indeed suggest that substantial proportions of patients are dropping out of ART.2 However, most existing studies are based on data from clinical cohorts, which have the important limitation that they usually count patients who have continued ART in another clinical site or who have died as being lost to follow-up, leading to over-estimates of nonretention. Population-based studies are urgently needed to distinguish facility switches and deaths from true non-retention—ie, the rates of patients who have started ART and are alive but have stopped taking antiretroviral drugs. For studies of interventions aiming to increase adherence to ART, non-retention might lead to selection eﬀects, which could bias estimates of eﬀect size (see the appendix to our Review1). Because retention within ART programmes precedes adherence, all the arguments for why an understanding of how to ensure good drug adherence is crucial in sub-Saharan Africa apply equally to interventions for increasing retention. However, as we have shown,3 although results from many randomised controlled trials of interventions to increase adherence to ART in sub-Saharan Africa have been reported, evidence from experimental studies of the eﬀectiveness of interventions to improve retention within ART programmes is very scarce. The importance of retention might further increase if countries implement treatment-as-prevention strategies. Additional eﬀorts might be needed for such strategies to successfully retain patients who are unlikely to have recovered from severe HIV disease with ART and who might thus be less motivated to remain in treatment than are patients who currently receive ART.4 To achieve the ultimate goals of HIV treatment programmes in subSaharan Africa—ie, to ensure that
patients with HIV infection can lead long, healthy, and productive lives—knowledge of interventions to ensure high levels of adherence to ART in the time immediately after treatment initiation is essential. As our systematic review shows,1 several strategies to achieve good short-term adherence to ART are emerging, including treatment supporters, directly observed therapy, and mobile-phone text messages. Future research needs to conﬁrm some of the early evidence and establish the cost-eﬀectiveness of interventions. More importantly, the medical community needs to learn how to ensure that all people needing ART initiate treatment and adhere well to their appointments and drug regimens throughout their lives, including in old age.5 We declare that we have no conﬂicts of interest.
*Till Bärnighausen, Krisda Chaiyachati, Natsayi Chimbindi, Jessica Haberer, Marie-Louise Newell [email protected]
Department of Global Health and Population, Harvard School of Public Health, Boston, MA 02115, USA (TB); Africa Centre for Health and Population Studies, University of KwaZulu-Natal, Mtubatuba, South Africa (TB, NC, M-LN); Yale School of Medicine, New Haven, CT, USA (KC); Massachusetts General Hospital, Center for Global Health, Boston, MA, USA (JH); and Centre for Paediatric Epidemiology and Biostatistics, University College London Institute of Child Health, London, UK (M-LN) 1
Bärnighausen T, Chaiyachati K, Chimbindi N, Peoples A, Haberer J, Newell ML. Interventions to increase antiretroviral adherence in sub-Saharan Africa: a systematic review of evaluation studies. Lancet Infect Dis 2011; 11: 942–51. Fox MP, Rosen S. Patient retention in antiretroviral therapy programs up to three years on treatment in sub-Saharan Africa, 2007–2009: systematic review. Trop Med Int Health 2010; 15 (suppl 1): 1–15. Bärnighausen T, Tanser F, Dabis F, Newell ML. Interventions to improve the performance of HIV health systems for treatment-as-prevention in sub-Saharan Africa: the experimental evidence. Curr Opin HIV AIDS 2012; 7: 140–50. Bärnighausen T, Salomon JA, Sangrujee N. HIV treatment as prevention: issues in economic evaluation. PLoS Med 2012; 9: e1001263. Nachega JB, Hsu Aj, Uthman OA, Spinewine A, Pham PA. Antiretroviral therapy adherence and drug-drug interactions in the aging HIV population. AIDS 2012, 26 (suppl 1): S39–53.
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