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

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 groups (CARGs) vs. standard-of-care facility-based ART delivery in Zimbabwe. METHODS: A three-arm, cluster-randomized, pragmatic non-inferiority trial was performed. Thirty healthcare 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 enrolment 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 pre-specified non-inferiority 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.