One year retention in community versus clinic-based adherence clubs for stable ART patients in South Africa C Hanrahan1, V Keyser2, S Schwartz1, P Soyizwaphi2, N West1, L Mutunga2, J Steingo2, J Bassett2, A Van Rie3 1Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA 2Witkoppen Health and Welfare Centre, Johannesburg, South Africa 3University of Antwerp, Antwerp, Belgium

Background- Adherence Clubs Adherence clubs are groups of 25-30 patients stable on ART Patients meet for counselling and medication pickup (~1 hour) Annual medical visit Facilitate task shifting and decongest busy clinics Experience from 2 observational studies in Cape Town: adherence clubs promote retention in care and viral suppression compared to clinic-based standard of care 57% reduction in loss-to-care (aHR 0.43, 95% CI:0.21-0.91) (Luque-Fernandez 2013) 67% reduction in virologic rebound (aHR 0.33, 95% CI: 0.16-0.67) (Luque-Fernandez 2013) 67% reduction in risk of LTFU (aHR: 0.33, 95% CI: 0.27-0.40) (Grimsrud 2016)

Background- Community vs clinic clubs No direct comparison of effectiveness or patient acceptability has been made between community and clinic-based clubs Systematic review of community versus clinic-based interventions (not specific to adherence clubs) suggest comparable retention and clinic outcomes (Nachega, in press 2016) Factors potentially at play: Stigma Convenience Cost Access to other health care (eg family planning, pediatric care) Others…???

Primary Study Objective Compare the effectiveness of community versus clinic-based adherence clubs on retention in care and viral suppression

Study Design Unblinded, open-label pragmatic randomized controlled trial Randomisation of clinic versus community-based clubs was stratified by participant area of residence 2 clubs per residential area (1 community, 1 clinic-based) created each month x 12 months

Primary Study Outcome Return to clinic-based standard of care (whether voluntary or for violating club rules—includes those LTFU from any care) AND Viral rebound (VL>400 copies/ml)

Study Setting Witkoppen Health and Welfare Centre High-volume primary care clinic in northern Johannesburg, South Africa Serves neighboring communities of Diepsloot and other informal settlements (~15-30 mins by public transport)

Intervention Description Each club has 25-30 participants Run by a lay HIV counsellor and supported by a PHCN Meet every 2 months Screened for pregnancy, TB symptoms and BP (if hypertensive) at each visit Community clubs held at community venues Participants were excluded from further participation in adherence clubs and returned back to clinic-based standard of care when: Missing a club visit and no ART pick-up within 5d Viral rebound (a viral load >400 copies/ml or 2 viral loads >50-400 copies/ml) Developing excluding comorbidity Falling pregnant Sending “buddy” for pickup 2x in a row Voluntary choice

Inclusion/Exclusion Criteria Inclusion Criteria Exclusion Criteria Age ≥ 18 years Currently on D4T containing regimen No change in ART regimen in previous year Currently pregnant or intending to become in ≤6 mos Virally suppressed for ≥ 12 months (confirmed at baseline) Current comorbidity or chronic illness (diabetes, epilepsy, active TB, cancer, mental illness, etc) Uncontrolled hypertension or treatment with >1 drug Attending clinic with HIV infected child Currently experiencing ART side effects

Inclusion/Exclusion Criteria Inclusion Criteria Exclusion Criteria Age ≥ 18 years Currently on D4T containing regimen No change in ART regimen in previous year Currently pregnant or intending to become in ≤6 mos Virally suppressed for ≥ 12 months (confirmed at baseline) Current comorbidity or chronic illness (diabetes, epilepsy, active TB, cancer, mental illness, etc) Uncontrolled hypertension or on treatment with >1 drug Viral suppression defined as: 2 most recent VL<400 copies/ml AND No more than 1 VL 50-400 copies/ml

Files of all ART patients pre-screened daily (~2000/month) Study Enrollment Files of all ART patients pre-screened daily (~2000/month) Screened by clinician n=1202 Enrollment: Feb 2014-Aug 2015 Ineligible n=356 (30%) Randomized n=846 (70%) Community Club n=434 (51%) Clinic Club n=412 (49%) Screening failure n=35 (8%) Screening failure n=26 (6%) Community Club n=399 (51%) Clinic Club n=386 (49%)

Files of all ART patients pre-screened daily (~2000/month) Study Enrollment Files of all ART patients pre-screened daily (~2000/month) Screened by clinician n=1202 Enrollment: Feb 2014-Aug 2015 Ineligible n=356 (30%) Randomized n=846 (70%) Not virally suppressed on baseline blood draw Community Club n=434 (51%) Clinic Club n=412 (49%) Screening failure n=35 (8%) Screening failure n=26 (6%) Community Club n=399 (51%) Clinic Club n=386 (49%)

Files of all ART patients pre-screened daily (~2000/month) Study Enrollment Files of all ART patients pre-screened daily (~2000/month) Screened by clinician n=1202 Enrollment: Feb 2014-Aug 2015 Ineligible n=356 (30%) Randomized n=846 (70%) Community Club n=434 (51%) Clinic Club n=412 (49%) Screening failure n=35 (8%) Screening failure n=26 (6%) Community Club n=399 (51%) Clinic Club n=386 (49%)

Baseline Participant Characteristics Community club Clinic club p Median age, years (IQR) 38 (32-43) 38 (33-43) 0.604 Female sex, n (%) 266 (68%) 244 (64%) 0.309 Unemployed, n (%) 94 (24%) 63 (17%) 0.041 Median CD4 count, cell/mm3 (IQR) 475 (346-657) 527 (376-678) 0.293 On Fixed Dose Combination, n (%) 347 (89%) 326 (88%) 0.263 Hypertensive, n (%) 19 (5%) 22 (6%) 0.255

Retention in club care and viral suppression 12 month proportion retained in care and virally suppressed: Community: 65% (95% CI: 59-70% ) Clinic: 77% (95% CI: 71-81%) Log-rank test: 0.003 Viral rebound: Community: 3% (95% CI: 1-4%) Clinic: 3% (95% CI:2-6%) p 0.476

Adjusted analysis Cox Proportional Hazards model adjusted for age, sex, regimen, baseline CD4 count and employment status Community club participants had a higher hazard of returning to clinic-based care or viral suppression compared to clinic-based clubs aHR 1.6 (95% CI: 1.1-2.3), p 0.006

Reasons for Club Discontinuation Community club Clinic club p Missing club visit and ART pick-up 112 (68%) 64 (58%) 0.088 Pregnancy 12 (7%) 13 (11%) 0.256 Viral rebound 10 (7%) 13 (12%) 0.148 2 consecutive late ART pick-ups 7 (4%) 7 (6%) 0.463 Voluntarily return to SOC 8 (5%) 6 (5%) 1.00 2 buddy pickups in a row 6 (4%) 0 (0%) 0.009 Developed comorbidity 2 (1%) Other 8 (7%) 0.299

Reasons for Club Discontinuation Community club Clinic club p Missing club visit and ART pick-up 112 (68%) 64 (58%) 0.088 Pregnancy 12 (7%) 13 (11%) 0.256 Viral rebound 10 (7%) 13 (12%) 0.148 2 consecutive late ART pick-ups 7 (4%) 7 (6%) 0.463 Voluntarily return to SOC 8 (5%) 6 (5%) 1.00 2 buddy pickups in a row 6 (4%) 0 (0%) 0.009 Developed comorbidity 2 (1%) Other 8 (7%) 0.299

Reasons for Club Discontinuation Community club Clinic club p Missing club visit and ART pick-up 112 (68%) 64 (58%) 0.088 Pregnancy 12 (7%) 13 (11%) 0.256 Viral rebound 10 (7%) 13 (12%) 0.148 2 consecutive late ART pick-ups 7 (4%) 7 (6%) 0.463 Voluntarily return to SOC 8 (5%) 6 (5%) 1.00 2 buddy pickups in a row 6 (4%) 0 (0%) 0.009 Developed comorbidity 2 (1%) Other 8 (7%) 0.299

Conclusions 12 month retention in club care was higher among participants in clinic-based clubs versus community based clubs Most common reason for return to SOC was missing club visits Viral rebound and voluntary withdrawal from clubs were rare Retention in care in community-based clubs in this pragmatic trial was much lower compared to published findings from Cape Town This trial: 66% Grimsrud, 2016: 94% Luque-Fernandez, 2013 : 97% Potential reasons: Lack of randomization (Luque-Fernandez: “only some stable patients were offered participation, based on the clinician’s enthusiasm for the model”) Differences in definition of outcome (retention in club care versus retention in any ART care)? Differences in eligibility criteria? Differences in approach? Differences in timing of outcome assessed?

Limitations Potential observer bias due to unblended treatment assignment Generalizability to other settings/ countries? Retention in HIV care (rather than club care) not presented here

Implications for public health Adherence clubs are currently a heterogeneous intervention, with different degrees of success Our finding suggest that facility-based adherence clubs are more effective than community-based clubs A better understanding of which aspects of adherence clubs are associated with success is needed Careful monitoring of loss to follow-up and virologic rebound is warranted when scaling up adherence clubs under routine care conditions

Acknowledgements Community Venues Afrika Tikkun - Diepsloot Witkoppen Health and Welfare Centre Adherence club patients Elry Rampela Galegole Mokoana Sr. Thobile Mthembu Gauta Moperero Lilian Ngwako Mutsa Mudavanhu Zanele Tshabalala Veronica Modise Collrane Frivold Lavina Ranjan Community Advisory Forum All clinicians Community Venues Afrika Tikkun - Diepsloot Department of Social Development Hall- Diepsloot Multi-purpose Hall- Cosmo City Msawawa - Kyasands St. Mungo Church - Bryanston Funding Source USAID Innovations Grant AID-674-A-12-00033 The contents of this presentation are the sole responsibility of Witkoppen Health and Welfare Centre and do not necessarily reflect the views of USAID or the United States Government.

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Reasons for Ineligibility Reason for ineligibility % Hypertensive-uncontrolled or on >1 drug 29% On current ART regimen <1 year 16% Not virally suppressed 13% Excluding comorbidity 9% Currently experiencing ART side effects 7% Intending to become pregnant in <6 mos Currently pregnant Attend clinic with HIV infected child Current TB 3% On D4T containing regimen 1%