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

Figure 1.
Figure 1.
Trial flow diagram. CV, coefficient of variation of cluster size; IQR, interquartile range; CARGs, community ART refill groups; 3MF, participants received three-monthly dispensing of ART at the facility; 3MC, participants received three months’ supply of ART in CARGs; 6MC, participants received 6 months’ supply of ART in CARGs.

References

    1. UNAIDS. UNAIDS Data 2019. 2019. . Accessed November 7th, 2019.
    1. 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.
    1. 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.
    1. 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.
    1. 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.
    1. 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.
    1. 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.
    1. 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.
    1. 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.
    1. 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.
    1. 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.
    1. 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.
    1. 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.
    1. 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.
    1. 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.
    1. UNAIDS. AIDSInfo. . Accessed November 6th, 2019.
    1. National AIDS Council; Ministry of Health and Child Care of Zimbabwe; UNAIDS. Global AIDS Response Progress report. 2018. . Accessed 06 November, 2019.
    1. 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.
    1. 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.
    1. 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.
    1. 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.
    1. 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.
    1. FHI 360. Zimbabwe HIV Care and Treatment Standard Operating Procedure for Community ART Refill Groups. 2016.
    1. 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.
    1. 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.
    1. 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.
    1. 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.
    1. 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.
    1. 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.
    1. 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.
    1. 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.
    1. Geng EH, Holmes CB. Research to improve differentiated HIV service delivery interventions: Learning to learn as we do. PLoS Medicine 2019;16(5):e1002809.

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