Outcomes of Three- Versus Six-Monthly Dispensing of Antiretroviral Treatment (ART) for Stable HIV Patients in Community ART Refill Groups: A Cluster-Randomized Trial in Zimbabwe
Geoffrey Fatti, Nicoletta Ngorima-Mabhena, Eula Mothibi, Trish Muzenda, Regis Choto, Tonderai Kasu, Taurayi A Tafuma, Nyika Mahachi, Kudakwashe C Takarinda, Tsitsi Apollo, Owen Mugurungi, Charles Chasela, Risa M Hoffman, Ashraf Grimwood, Geoffrey Fatti, Nicoletta Ngorima-Mabhena, Eula Mothibi, Trish Muzenda, Regis Choto, Tonderai Kasu, Taurayi A Tafuma, Nyika Mahachi, Kudakwashe C Takarinda, Tsitsi Apollo, Owen Mugurungi, Charles Chasela, Risa M Hoffman, Ashraf Grimwood
Abstract
Introduction: Multimonth dispensing (MMD) of antiretroviral treatment (ART) aims to reduce patient-related barriers to access long-term treatment and improve health system efficiency. However, randomized evidence of its clinical effectiveness is lacking. We compared MMD within community ART refill groups (CARGs) vs. standard-of-care facility-based ART delivery in Zimbabwe.
Methods: A three-arm, cluster-randomized, pragmatic noninferiority trial was performed. Thirty health care facilities and associated CARGs were allocated to either ART collected three-monthly at facility (3MF, control); ART delivered three-monthly in CARGs (3MC); or ART delivered six-monthly in CARGs (6MC). Stable adults receiving ART ≥six months with baseline viral load (VL) <1000 copies/ml were eligible. Retention in ART care (primary outcome) and viral suppression (VS) 12 months after enrollment were compared, using regression models specified for clustering (ClinicalTrials.gov: NCT03238846).
Results: 4800 participants were recruited, 1919, 1335, and 1546 in arms 3MF, 3MC, and 6MC, respectively. For retention, the prespecified noninferiority limit (-3.25%, risk difference [RD]) was met for comparisons between all arms, 3MC (94.8%) vs. 3MF (93.0%), adjusted RD = 1.1% (95% CI: -0.5% to 2.8%); 6MC (95.5%) vs. 3MF: aRD = 1.2% (95% CI: -1.0% to 3.6%); and 6MC vs. 3MC: aRD = 0.1% (95% CI: -2.4% to 2.6%). VL completion at 12 months was 49%, 45%, and 8% in 3MF, 3MC, and 6MC, respectively. VS in 3MC (99.7%) was high and not different to 3MF (99.1%), relative risk = 1.0 (95% CI: 1.0-1.0). VS was marginally reduced in 6MC (92.9%) vs. 3MF, relative risk = 0.9 (95% CI: 0.9-1.0).
Conclusion: Retention in CARGs receiving three- and six-monthly MMD was noninferior versus standard-of-care facility-based ART delivery. VS in 3MC was high. VS in six-monthly CARGs requires further evaluation.
Conflict of interest statement
No conflicts of interest are declared.
Figures
References
- UNAIDS. UNAIDS Data 2019. 2019. . Accessed November 7th, 2019.
- Grimsrud A, Bygrave H, Doherty M, et al. Reimagining HIV service delivery: the role of differentiated care from prevention to suppression. J Int AIDS Soc 2016;19(1):21484.
- Kates J, Wexler A, Lief E. Financing the response to HIV in low- and middle-income countries: international assistance from Donor Governments in 2015. 2016. . Accessed April 15th, 2017.
- Maddison A, Schlech W. Will universal access to antiretroviral therapy ever be possible? The health care worker challenge. Can J Infect Dis Med Microbiol 2010;21(1):e64–e69.
- Eshun-Wilson I, Mukumbwa-Mwenechanya M, Kim HY, et al. Differentiated Care Preferences of Stable Patients on Antiretroviral Therapy in Zambia: A Discrete Choice Experiment. J Acquir Immune Defic Syndr 2019;81(5):540–546.
- Prust ML, Banda CK, Nyirenda R, et al. Multi-month prescriptions, fast-track refills, and community ART groups: results from a process evaluation in Malawi on using differentiated models of care to achieve national HIV treatment goals. J Int AIDS Soc 2017;20(Suppl 4):21650.
- Phillips A, Shroufi A, Vojnov L, et al. Sustainable HIV treatment in Africa through viral-load-informed differentiated care. Nature 2015;528(7580):S68–S76.
- Decroo T, Rasschaert F, Telfer B, Remartinez D, Laga M, Ford N. Community-based antiretroviral therapy programs can overcome barriers to retention of patients and decongest health services in sub-Saharan Africa: a systematic review. International Health 2013;5(3):169–179.
- Kim MH, Wanless RS, Caviness AC, et al. Multimonth Prescription of Antiretroviral Therapy Among Children and Adolescents: Experiences From the Baylor International Pediatric AIDS Initiative in 6 African Countries. J Acquir Immune Defic Syndr 2018;78(Suppl 2):S71–s80.
- Mody A, Roy M, Sikombe K, et al. Improved Retention With 6-Month Clinic Return Intervals for Stable Human Immunodeficiency Virus-Infected Patients in Zambia. Clin Infect Dis 2018;66(2):237–243.
- Wringe A, Cawley C, Szumilin E, et al. Retention in care among clinically stable antiretroviral therapy patients following a six-monthly clinical consultation schedule: findings from a cohort study in rural Malawi. J Int AIDS Soc 2018;21(11):e25207.
- Grimsrud A, Patten G, Sharp J, Myer L, Wilkinson L, Bekker LG. Extending dispensing intervals for stable patients on ART. J Acquir Immune Defic Syndr 2014;66(2):e58–60.
- Mutasa-Apollo T, Ford N, Wiens M, et al. Effect of frequency of clinic visits and medication pick-up on antiretroviral treatment outcomes: a systematic literature review and meta-analysis. J Int AIDS Soc 2017;20(Suppl 4):21647.
- Puttkammer N, Rodriguez T, Robin E, et al. Multi-Month Scripting (MMS) And Retention On HIV Antiretroviral Therapy In Haiti. Paper presented at: Conference on Retroviruses and Opportunistic Infections; 4-7 March, 2018; Boston, MA, USA.
- Lebelo K, Cassidy T, Grimsrud A, et al. Twelve-month retention and viral load outcomes from a noninferiority cluster randomized trial extending adherence club ART refill dispensing intervals to 6-monthly. Paper presented at: 10th IAS Conference on HIV Science; 21-24 July, 2019; Mexico City, Mexico.
- UNAIDS. AIDSInfo. . Accessed November 6th, 2019.
- National AIDS Council; Ministry of Health and Child Care of Zimbabwe; UNAIDS. Global AIDS Response Progress report. 2018. . Accessed 06 November, 2019.
- Decroo T, Koole O, Remartinez D, et al. Four-year retention and risk factors for attrition among members of community ART groups in Tete, Mozambique. Trop Med Int Health 2014;19(5):514–521.
- Rasschaert F, Decroo T, Remartinez D, et al. Adapting a community-based ART delivery model to the patients’ needs: a mixed methods research in Tete, Mozambique. BMC public health 2014;14(1):364.
- Rasschaert F, Telfer B, Lessitala F, et al. A qualitative assessment of a community antiretroviral therapy group model in Tete, Mozambique. PLoS One 2014;9(3):e91544.
- Zimbabwe Ministry of Health and Child Care. Operational and service delivery manual for the prevention, care and treatment of HIV in Zimbabwe. 2017. . Accessed 14 August 2017.
- Fatti G, Ngorima-Mabhena N, Chirowa F, et al. The effectiveness and cost-effectiveness of 3- vs. 6-monthly dispensing of antiretroviral treatment (ART) for stable HIV patients in community ART-refill groups in Zimbabwe: study protocol for a pragmatic, cluster-randomized trial. Trials 2018;19(1):79.
- FHI 360. Zimbabwe HIV Care and Treatment Standard Operating Procedure for Community ART Refill Groups. 2016.
- Ivers NM, Halperin IJ, Barnsley J, et al. Allocation techniques for balance at baseline in cluster randomized trials: a methodological review. Trials 2012;13(1):120.
- World Health Organization. Operations manual for delivery of HIV prevention, care and treatment at primary health centres in high-prevalence, resource-constrained settings. Edition 1 for field testing and country adaptation. 2008. . Accessed 16 Sep, 2016.
- Shepherd BE, Blevins M, Vaz LME, et al. Impact of Definitions of Loss to Follow-up on Estimates of Retention, Disease Progression, and Mortality: Application to an HIV Program in Mozambique. American Journal of Epidemiology 2013;178(5):819–828.
- Fairall L, Bachmann MO, Lombard C, et al. Task shifting of antiretroviral treatment from doctors to primary-care nurses in South Africa (STRETCH): a pragmatic, parallel, cluster-randomised trial. Lancet 2012;380(9845):889–898.
- Pedroza C, Thanh Truong VT. Performance of models for estimating absolute risk difference in multicenter trials with binary outcome. BMC Med Res Methodol 2016;16(1):113.
- Huang S, Fiero MH, Bell ML. Generalized estimating equations in cluster randomized trials with a small number of clusters: Review of practice and simulation study. Clinical Trials 2016;13(4):445–449.
- Bochner AF, Meacham E, Mhungu N, et al. The rollout of Community ART Refill Groups in Zimbabwe: a qualitative evaluation. J Int AIDS Soc 2019;22(8):e25393.
- Casale M, Carlqvist A, Cluver L. Recent Interventions to Improve Retention in HIV Care and Adherence to Antiretroviral Treatment Among Adolescents and Youth: A Systematic Review. AIDS Patient Care STDS 2019;33(6):237–252.
- Geng EH, Holmes CB. Research to improve differentiated HIV service delivery interventions: Learning to learn as we do. PLoS Medicine 2019;16(5):e1002809.
Source: PubMed