Outcomes of Differentiated Models of Care: Multi-Month Dispensing (MMD) and Community ART Refill Groups (CARGs) in Stable ART Patients

This study will use a cluster (facility) randomized trial with 3 arms; patients receiving 3 monthly ART supply at facilities-standard of care (3MF) (Control group), patients receiving 3 monthly ART supply at newly formed CARGs (3MC) and patients receiving 6 monthly ART supply at newly formed CARGs (6MC). Participants will be followed up for 24 months. A total of 30 study clusters (facilities) will be randomization, into the three study arms; 10 clusters per arm stratified 2 urban, 8 rural.

Study Setting and study population The study population is HIV-infected adults over the age of 18 years recruited from health facilities in U.S. President's Emergency Plan for AIDS Relief (PEPFAR) Zimbabwe scale-up districts (using existing national records of patients in the ART registers) that have been stable on a standard first-line ART treatment regimen for at least 6 months.

Facilities from Chitungwiza Municipality, Matebeleland South Province, Masvingo Province and Mberengwa district will be purposively selected to be the urban/periurban and rural settings in the study. These areas were selected as they have PEPFAR Zimbabwe scale-up priority facilities, high numbers of patients on ART and have prioritized implementation of CARGs. These locations are also viewed to be good representations of PEPFAR Zimbabwe scale-up priority facilities, hence are likely to improve the generalizability of the study findings to the study population. As contexts differ between rural and urban/periurban settings, it is important to determine the effectiveness of MMD within CARGs within both contexts.

Sampling and Sample size Sample sizes were determined for a cluster-randomized noninferiority trial, using PASS v.14 (TM) software. Sample size estimates were calculated for the primary outcome of retention in care at 12 months. The probability of patient attrition twelve months after study enrolment in the control group (3MF) is assumed to be 5%, derived from the relative difference in patient retention between 12 and 24 months from the 2015 Zimbabwe UNAIDS Global AIDS Response progress report. An intracluster correlation coefficient (ICC) of 0.01 for patient retention/attrition amongst stable ART patients is assumed. The noninferiority limit is specified as 3.25%. Assuming α=0.05, power of 85%, using one-sided Z-test (unpooled) test statistic, 182 participants per facility will be required with a total sample size of 5460 participants. A sample size re-estimation during accrual will increase the total sample size to approximately 5760; 192 enrolled participants per study site and 1,920 participants per arm. As retention in care is the primary outcome, no adjustment for loss to follow-up needs to be made.

Study procedures As this is operational research, the study will not interfere with routine patient management and will follow national guidelines. The health care worker assesses each patient's clinical notes to establish stability and study inclusion. Once informed consent is obtained, a baseline questionnaire will be applied to record demographic characteristics and the patients clinical and ART history. Patients will receive care based on their study ARM and relevant SOP. Patient files and CARG tools will be reviewed and data collected at each ART refill. Viral loads will be repeated annually.