1. The Methods for Improving Reproductive Health in Africa (MIRA) Study SOC PROGRAM Liz Montgomery Women’s Global Health Imperative RTI International GCM SOC Consultation June 19, 2008

2. Partners Women’s Global Health Imperative: University of California San Francisco Ibis Reproductive Health, USA & RSA University of Zimbabwe-UCSF Collaborative Research Programme, Zimbabwe Medical Research Council, Durban RSA Perinatal HIV Research Unit, Johannesburg, RSA Funder: Bill & Melinda Gates Foundation

3. Study Aims To examine the effectiveness of the diaphragm and lubricant gel for preventing HIV acquisition in women Primary endpoint: HIV acquisition Secondary endpoints: cervical STIs (GC & CT)

4. Study Design All women received risk reduction counseling, free male condoms and diagnosis and treatment of curable STIs +

5. MIRA Trial Sites Total n = 5045 UZ-UCSF Harare, Zimbabwe n=2502 PHRU Soweto, South Africa n=1028 MRC Durban, South Africa n=1515

6. Zimbabwe Standard of Care at start of MIRA trial ARV’s available only as part of research studies. These are few and small, but UZ- UCSF has direct relationships with the investigators of these studies. MOH planned to roll out nationwide generic ART programme at tertiary hospitals, but unknown exactly when this would happen

7. MIRA: Current Standard of Care Screened HIV+ MIRA women: –Professional pre and post-test counseling for woman and partner –STI screening and treatment for woman and partner –2-week follow-up supportive counseling visit at MIRA –Referral to social services, support groups and “moving-on” clubs, HIV care organizations –Referral to research studies providing ART (DART, Duke) and studies specializing in discordant couples (HPTN 052)

8. MIRA: Current Standard of Care Seroconverters: –Same as screened HIV+ women, except that seroconverters stay in study, therefore have ongoing access to clinical care for themselves and partners. This includes pregnancy and STI screening and treatment for any medical problems.

9. Standard of Care “Moving target” - National ARV programmes and “standard of care” for research studies evolving as study progressed; –Gates Foundation aware that what they approved for MIRA would set a precedent –Equity, sustainability huge concerns

10. MIRA SOC program - theory (Official) Overall goal was to transition all MIRA seroconverters into the National ARV Programme in Zimbabwe or South Africa before the end of the trial period (thereby ensuring sustainability) Explicitly, we did not plan to assume responsibility for care and treatment

11. Timeline MIRA initiated 2003200420052006 2007 2008 MIRA SOC initiated MIRA ended SOC IE interviews

12. MIRA SOC – Operationalization Durban: MOUs with organizations, clinics and hospitals Soweto: Referral to co-located facility with psychosocial support and ART Harare: Referral to local psychosocial support and OI clinics (in theory) At all sites: referral to ART studies viewed as equivalent to National Tx Programmes

13. Zimbabwe in reality Social welfare> OI clinic/ CD4 testing> ART –CD4 testing done by trial, trial paid for small subsidy for cost of ART if needed, during study –Paper at social welfare –National shortages/ slots ran out Connections

14. MIRA Standard of Care Program Results UZ- UCSFMRCPHRUTotal PROGRAM OVERVIEW Total number of seroconverters12515349327 Received information about SOC from MIRA staff913522148 Contacted and did not decline, but never attended SOC visit at MIRA clinic3121025 Not interested or LTFU296814111 Declined because already participating in similar program for HIV-positives/satisfied with outside care036339 Deceased2204 LINKAGES TO OUTSIDE SERVICES Opportunistic Infection facilities Referred802723130 Enrolled5917884 Other research studies Referred13301154 Enrolled6301147 ARV TREATMENT Received CD4 test at MIRA-related clinic872924140 Accessed ARVs133218 Waitlisted ARVs3003

15. Summary of linkage success Harare: 74% Durban: 37% Soweto: 69% 13 of 300+ accessing ARVs

16. SOC Challenges Country-level: National programmes are new and face challenges of their own – staff shortages, ARV shortages (Zim); Study-level: Difficult for research study team to manage a “care” package in a variety of different settings, with varying resources, different relationships with local organizations, and different resources Participant-level: Some participants difficult to reach, in denial about serostatus/ need for ARVs, some already passed away by the time SOC implemented

17. Key unanswered questions Why such low uptake Where are they now?