1. Care for seroconverters in CONRAD’s Cellulose Sulfate HIV Prevention Trial Lut Van Damme Global Campaign meeting 19-20 June 2008

2. The trial

3. Objectives and Endpoints  Primary:  Effectiveness in preventing male-to-female transmission of HIV-infection through vaginal intercourse by comparing HIV incidence in both arms (ITT)  Secondary:  Effectiveness in preventing male-to-female transmission of gonorrhea and chlamydia infection through vaginal intercourse by comparing the incidence in both arms (ITT – time to first event)

4. Design and Population  Design: Randomized (1:1 allocation), placebo- controlled, blinded, two-arm, multicenter  Study Population: HIV negative women, 18 years or older, with multiple partners

5. Organizational Chart and Sites CONRAD FHI ITM BENIN PI- Michel Alary Co-PI- Fernand Guedou INDIA-BA PI- Marissa Becker Co-PI- Reynold Washington INDIA-CH PI- Suniti Solomon UGANDA PI- Florence Mirembe SOUTH AFRICA PI- Roshini Govinden

6. Sample Size and Power Planned sample size = 2,574 HIV negative women Assumptions:  50% effectiveness of CS  2-sided significance level of 0.05  80% power  80% of participants completing 12-month follow up  HIV-incidence in control arm: 4%

7. (Interim) Analysis and IDMC  One planned interim analysis with Independent Data Monitoring Committee meeting after ~ 33 HIV seroconversions - 26 January 2007  Guidance from the IDMC requested if p<0.10 in the direction of harm (i.e. stop for harm or futility)

8. Population Tree Screened 2985 Enrolled 1428 3 PCR Positive CSPlaceboTotal ITT population7177081425 HIV analysis7066921398 Lost to follow-up10.7%9.0%9.9% Discontinued early2.4%1.0%1.7% Completed final visit86.9%90.0%88.4%

9. Results Events RR (95% CI) Two-sided p value CSPlacebo HIV (Interim)2411 2.23 (1.05, 5.03)0.02 HIV (ITT - Final)2516 1.61 (0.86, 3.01)0.13 HIV (per protocol)2311 2.18 (1.06, 4.47)0.03 Gonorrhea5349 1.10 (0.74, 1.62)0.63 Chlamydia3752 0.71 (0.47, 1.08)0.11

10. KM Estimates of Incident HIV Infection Probabilities, by Treatment Group CS Placebo

11. The N9 (COL-1492) experience and impact on my perception of care

12. Care in the CS trial  Senior management and funders easily agreed with the principal to provide care  Original idea:  5years (arbitrarily decided)  A rato of seroconverters within a site  Funding based on cost of local care (budgets provided by sites)

13. Issues  Care is more than ARV alone  Investigators cannot be held responsible for the funds (care needed after trial)  Giving money to individual women was considered not a good option (use of money for other things than her care)  In many countries: ARV are free  sites can best decide on how to spend the money in the best way as to benefit care (in general)

14. Outcome  Funds would be given to referral clinics – transfer via CS study teams  Written agreements necessary  Some sites were ARV clinics

15. Study closure  CONRAD delegates the care of seroconverters to local study team  Local study team makes agreement with referral clinic(s)  Contract between CONRAD and local study team to transfer the funding – agreement between local site and referral clinic attached to this contract  CONRAD has reserved the right to do financial audits of the contracted (clinical) sites