Participation in adherence clubs and on-time drug pickup among HIV-infected adults in Zambia: A matched-pair cluster randomized trial

Autoři: Monika Roy aff001;  Carolyn Bolton-Moore aff002;  Izukanji Sikazwe aff002;  Mpande Mukumbwa-Mwenechanya aff002;  Emilie Efronson aff002;  Chanda Mwamba aff002;  Paul Somwe aff002;  Estella Kalunkumya aff002;  Mwansa Lumpa aff002;  Anjali Sharma aff002;  Jake Pry aff002;  Wilbroad Mutale aff002;  Peter Ehrenkranz aff005;  David V. Glidden aff001;  Nancy Padian aff006;  Stephanie Topp aff007;  Elvin Geng aff001;  Charles B. Holmes aff008
Působiště autorů: University of California, San Francisco, San Fancisco, California, United States of America aff001;  Centre for Infectious Disease Research in Zambia, Lusaka, Zambia aff002;  University of Alabama, Tuscaloosa, Alabama, United States of America aff003;  University of California, Davis, Davis, California, United States of America aff004;  Bill and Melinda Gates Foundation, Seattle, Washington, United States of America aff005;  University of California, Berkeley, Berkeley, California, United States of America aff006;  James Cook University, Townsville, Queensland, Australia aff007;  Johns Hopkins University, Baltimore, Maryland, United States of America aff008;  Center for Global Health Practice and Impact, Georgetown University School of Medicine, Washington, District of Columbia, United States of America aff009
Vyšlo v časopise: Participation in adherence clubs and on-time drug pickup among HIV-infected adults in Zambia: A matched-pair cluster randomized trial. PLoS Med 17(7): e1003116. doi:10.1371/journal.pmed.1003116
Kategorie: Research Article
doi: 10.1371/journal.pmed.1003116



Current models of HIV service delivery, with frequent facility visits, have led to facility congestion, patient and healthcare provider dissatisfaction, and suboptimal quality of services and retention in care. The Zambian urban adherence club (AC) is a health service innovation designed to improve on-time drug pickup and retention in HIV care through off-hours facility access and pharmacist-led group drug distribution. Similar models of differentiated service delivery (DSD) have shown promise in South Africa, but observational analyses of these models are prone to bias and confounding. We sought to evaluate the effectiveness and implementation of ACs in Zambia using a more rigorous study design.

Methods and findings

Using a matched-pair cluster randomized study design ( NCT02776254), 10 clinics were randomized to intervention (5 clinics) or control (5 clinics). At each clinic, between May 19 and October 27, 2016, a systematic random sample was assessed for eligibility (HIV+, age ≥ 14 years, on ART >6 months, not acutely ill, CD4 count not <200 cells/mm3) and willingness to participate in an AC. Clinical and antiretroviral drug pickup data were obtained through the existing electronic medical record. AC meeting attendance data were collected at intervention facilities prospectively through October 28, 2017. The primary outcome was time to first late drug pickup (>7 days late). Intervention effect was estimated using unadjusted Kaplan–Meier survival curves and a Cox proportional hazards model to derive an adjusted hazard ratio (aHR). Medication possession ratio (MPR) and implementation outcomes (adoption, acceptability, appropriateness, feasibility, and fidelity) were additionally evaluated as secondary outcomes. Baseline characteristics were similar between 571 intervention and 489 control participants with respect to median age (42 versus 41 years), sex (62% versus 66% female), median time since ART initiation (4.8 versus 5.0 years), median CD4 count at study enrollment (506 versus 533 cells/mm3), and baseline retention (53% versus 55% with at least 1 late drug pickup in previous 12 months). The rate of late drug pickup was lower in intervention participants compared to control participants (aHR 0.26, 95% CI 0.15–0.45, p < 0.001). Median MPR was 100% in intervention participants compared to 96% in control participants (p < 0.001). Although 18% (683/3,734) of AC group meeting visits were missed, on-time drug pickup (within 7 days) still occurred in 51% (350/683) of these missed visits through alternate means (use of buddy pickup or early return to the facility). Qualitative evaluation suggests that the intervention was acceptable to both patients and providers. While patients embraced the convenience and patient-centeredness of the model, preference for traditional adherence counseling and need for greater human resources influenced intervention appropriateness and feasibility from the provider perspective. The main limitations of this study were the small number of clusters, lack of viral load data, and relatively short follow-up period.


ACs were found to be an effective model of service delivery for reducing late ART drug pickup among HIV-infected adults in Zambia. Drug pickup outside of group meetings was relatively common and underscores the need for DSD models to be flexible and patient-centered if they are to be effective.

Trial registration NCT02776254.

Klíčová slova:

Antiretroviral therapy – Drug adherence – Drug delivery – Employment – HIV – Patients – South Africa – Zambia


1. Hardon AP, Akurut D, Comoro C, Ekezie C, Irunde HF, Gerrits T, et al. Hunger, waiting time and transport costs: time to confront challenges to ART adherence in Africa. AIDS Care. 2007;19(5):658–65. doi: 10.1080/09540120701244943 17505927

2. Wanyenze RK, Wagner G, Alamo S, Amanyire G, Ouma J, Kwarisima D, et al. Evaluation of the efficiency of patient flow at three HIV clinics in Uganda. AIDS Patient Care STDS. 2010;24(7):441–6. doi: 10.1089/apc.2009.0328 20578908

3. Alamo ST, Wagner GJ, Ouma J, Sunday P, Marie L, Colebunders R, et al. Strategies for optimizing clinic efficiency in a community-based antiretroviral treatment programme in Uganda. AIDS Behav. 2013;17(1):274–83. doi: 10.1007/s10461-012-0199-9 22610422

4. Roy M, Holmes C, Sikazwe I, Savory T, Mwanza MW, Bolton Moore C, et al. Application of a multistate model to evaluate visit burden and patient stability to improve sustainability of human immunodeficiency virus treatment in Zambia. Clin Infect Dis. 2018;67(8):1269–77. doi: 10.1093/cid/ciy285 29635466

5. Fox MP, Rosen S. Retention of adult patients on antiretroviral therapy in low- and middle-income countries: systematic review and meta-analysis 2008–2013. J Acquir Immune Defic Syndr. 2015;69(1):98–108. doi: 10.1097/QAI.0000000000000553 25942461

6. Kinfu Y, Dal Poz MR, Mercer H, Evans DB. The health worker shortage in Africa: are enough physicians and nurses being trained? Bull World Health Organ. 2009;87:225–30. doi: 10.2471/blt.08.051599 19377719

7. Lambdin BH, Micek MA, Koepsell TD, Hughes JP, Sherr K, Pfeiffer J, et al. Patient volume, human resource levels, and attrition from HIV treatment programs in central Mozambique. J Acquir Immune Defic Syndr. 2011;57(3):e33–9. doi: 10.1097/QAI.0b013e3182167e90 21372723

8. Willcox ML, Peersman W, Daou P, Diakite C, Bajunirwe F, Mubangizi V, et al. Human resources for primary health care in sub-Saharan Africa: progress or stagnation? Hum Resour Health. 2015;13:76. doi: 10.1186/s12960-015-0073-8 26358250

9. Grimsrud A, Bygrave H, Doherty M, Ehrenkranz P, Ellman T, Ferris R, et al. Reimagining HIV service delivery: the role of differentiated care from prevention to suppression. J Int AIDS Soc. 2016;19(1):21484. doi: 10.7448/IAS.19.1.21484 27914186

10. Duncombe C, Rosenblum S, Hellmann N, Holmes C, Wilkinson L, Biot M, et al. Reframing HIV care: putting people at the centre of antiretroviral delivery. Trop Med Int Health. 2015;20(4):430–47. doi: 10.1111/tmi.12460 25583302

11. Luque-Fernandez MA, Van Cutsem G, Goemaere E, Hilderbrand K, Schomaker M, Mantangana N, et al. Effectiveness of patient adherence groups as a model of care for stable patients on antiretroviral therapy in Khayelitsha, Cape Town, South Africa. PLoS ONE. 2013;8(2):e56088. doi: 10.1371/journal.pone.0056088 23418518

12. Tsondai PR, Wilkinson LS, Grimsrud A, Mdlalo PT, Ullauri A, Boulle A. High rates of retention and viral suppression in the scale-up of antiretroviral therapy adherence clubs in Cape Town, South Africa. J Int AIDS Soc. 2017;20(Suppl 4):51–7. doi: 10.7448/IAS.20.5.21649 28770595

13. Grimsrud A, Lesosky M, Kalombo C, Bekker LG, Myer L. Implementation and operational research: community-based adherence clubs for the management of stable antiretroviral therapy patients in Cape Town, South Africa: a cohort study. J Acquir Immune Defic Syndr. 2016;71(1):e16–23. doi: 10.1097/QAI.0000000000000863 26473798

14. Khabala KB, Edwards JK, Baruani B, Sirengo M, Musembi P, Kosgei RJ, et al. Medication adherence clubs: a potential solution to managing large numbers of stable patients with multiple chronic diseases in informal settlements. Trop Med Int Health. 2015;20(10):1265–70. doi: 10.1111/tmi.12539 25962952

15. Joint United Nations Programme on HIV/AIDS. UNAIDS data 2017. Geneva: Joint United Nations Programme on HIV/AIDS; 2017.

16. McCarthy EA, Subramaniam HL, Prust ML, Prescott MR, Mpasela F, Mwango A, et al. Quality improvement intervention to increase adherence to ART prescription policy at HIV treatment clinics in Lusaka, Zambia: a cluster randomized trial. PLoS ONE. 2017;12(4):e0175534. doi: 10.1371/journal.pone.0175534 28419106

17. Hayes RJ, Moulton LH. Cluster randomized trials. New York: Chapman and Hall/CRC; 2009.

18. R Development Core Team. R: a language and environment for statistical computing. Vienna: R Foundation for Statistical Computing; 2013.

19. Therneau TM, Grambsch PM. modeling survival data: extending the Cox model. New York: Springer; 2000. 350 p.

20. Proctor E, Silmere H, Raghavan R, Hovmand P, Aarons G, Bunger A, et al. Outcomes for implementation research: conceptual distinctions, measurement challenges, and research agenda. Adm Policy Ment Health. 2011;38(2):65–76. doi: 10.1007/s10488-010-0319-7 20957426

21. Hong SY, Jerger L, Jonas A, Badi A, Cohen S, Nachega JB, et al. Medication possession ratio associated with short-term virologic response in individuals initiating antiretroviral therapy in Namibia. PLoS ONE. 2013;8(2):e56307. doi: 10.1371/journal.pone.0056307 23509605

22. Vinikoor MJ, Schuttner L, Moyo C, Li M, Musonda P, Hachaambwa LM, et al. Short communication: late refills during the first year of antiretroviral therapy predict mortality and program failure among HIV-infected adults in urban Zambia. AIDS Res Hum Retroviruses. 2014;30(1):74–7. doi: 10.1089/AID.2013.0167 23924188

23. Haberer JE, Musinguzi N, Boum Y 2nd, Siedner MJ, Mocello AR, Hunt PW, et al. Duration of antiretroviral therapy adherence interruption is associated with risk of virologic rebound as determined by real-time adherence monitoring in rural Uganda. J Acquir Immune Defic Syndr. 2015;70(4):386–92. doi: 10.1097/QAI.0000000000000737 26110445

24. Blacher RJ, Muiruri P, Njobvu L, Mutsotso W, Potter D, Ong’ech J, et al. How late is too late? Timeliness to scheduled visits as an antiretroviral therapy adherence measure in Nairobi, Kenya and Lusaka, Zambia. AIDS Care. 2010;22(11):1323–31. doi: 10.1080/09540121003692235 20711886

25. Parienti JJ, Das-Douglas M, Massari V, Guzman D, Deeks SG, Verdon R, et al. Not all missed doses are the same: sustained NNRTI treatment interruptions predict HIV rebound at low-to-moderate adherence levels. PLoS ONE. 2008;3(7):e2783. doi: 10.1371/journal.pone.0002783 18665246

26. Genberg BL, Wilson IB, Bangsberg DR, Arnsten J, Goggin K, Remien RH, et al. Patterns of antiretroviral therapy adherence and impact on HIV RNA among patients in North America. AIDS. 2012;26(11):1415–23. doi: 10.1097/QAD.0b013e328354bed6 22767342

27. Efronson E, Mukumba-Mwenechanya M, Sharma A, Chilala C, Mutale W, Topp SM. Perceived need for model- and audience-specific communication for successful implementation of differentiated care in Zambia. International Conference on AIDS and STIs in Africa; 2017 Dec 4–9; Abidjan, Côte d’Ivoire.

28. Aitken SC, Wallis CL, Stevens W, de Wit TR, Schuurman R. Stability of HIV-1 nucleic acids in dried blood spot samples for HIV-1 drug resistance genotyping. PLoS ONE. 2015;10(7):e0131541. doi: 10.1371/journal.pone.0131541 26147689

29. Lofgren SM, Morrissey AB, Chevallier CC, Malabeja AI, Edmonds S, Amos B, et al. Evaluation of a dried blood spot HIV-1 RNA program for early infant diagnosis and viral load monitoring at rural and remote healthcare facilities. AIDS. 2009;23(18):2459–66. doi: 10.1097/QAD.0b013e328331f702 19741481

30. Stevens W, Erasmus L, Moloi M, Taleng T, Sarang S. Performance of a novel human immunodeficiency virus (HIV) type 1 total nucleic acid-based real-time PCR assay using whole blood and dried blood spots for diagnosis of HIV in infants. J Clin Microbiol. 2008;46(12):3941–5. doi: 10.1128/JCM.00754-08 18923017

31. Hanrahan C KV, Schwartz S, Mudavanhu M, West N, Mutunga L, Steingo J, et al. Retention in community versus clinic-based adherence clubs for stable ART patients in South Africa: 24 month final outcomes from an RCT. 9th IAS Conference on HIV Science; 2017 Jul 23–26; Paris, France.

32. MacGregor H, McKenzie A, Jacobs T, Ullauri A. Scaling up ART adherence clubs in the public sector health system in the Western Cape, South Africa: a study of the institutionalisation of a pilot innovation. Global Health. 2018;14(1):40. doi: 10.1186/s12992-018-0351-z 29695268

33. Venables E, Towriss C, Rini Z, Nxiba X, Cassidy T, Tutu S, et al. Patient experiences of ART adherence clubs in Khayelitsha and Gugulethu, Cape Town, South Africa: a qualitative study. PLoS ONE. 2019;14(6):e0218340. doi: 10.1371/journal.pone.0218340 31220116

34. Topp SM, Mwamba C, Sharma A, Mukamba N, Beres LK, Geng E, et al. Rethinking retention: mapping interactions between multiple factors that influence long-term engagement in HIV care. PLoS ONE. 2018;13(3):e0193641. doi: 10.1371/journal.pone.0193641 29538443

35. Mwamba C, Sharma A, Mukamba N, Beres L, Geng E, Holmes CB, et al. ‘They care rudely!’: resourcing and relational health system factors that influence retention in care for people living with HIV in Zambia. BMJ Glob Health. 2018;3(5):e001007. doi: 10.1136/bmjgh-2018-001007 30483408

36. Joint United Nations Programme on HIV/AIDS, Médecins Sans Frontières. Community-based antiretroviral therapy delivery: experiences of Médecins Sans Frontières. Geneva: Joint United Nations Programme on HIV/AIDS; 2015 [cited 2020 Jun3]. Available from:

37. Mukumbang FC, Van Belle S, Marchal B, van Wyk B. An exploration of group-based HIV/AIDS treatment and care models in Sub-Saharan Africa using a realist evaluation (Intervention-Context-Actor-Mechanism-Outcome) heuristic tool: a systematic review. Implement Sci. 2017;12(1):107. doi: 10.1186/s13012-017-0638-0 28841894

38. Mukumbang FC, Van Belle S, Marchal B, van Wyk B. Exploring ‘generative mechanisms’ of the antiretroviral adherence club intervention using the realist approach: a scoping review of research-based antiretroviral treatment adherence theories. BMC Public Health. 2017;17(1):385. doi: 10.1186/s12889-017-4322-8 28472938

39. Giraudeau B, Ravaud P. Preventing bias in cluster randomised trials. PLoS Med. 2009;6(5):e1000065. doi: 10.1371/journal.pmed.1000065 19536323

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