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

The trial

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)

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

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

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%

(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)

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

Results Events RR (95% CI) Two-sided p value CSPlacebo HIV (Interim) (1.05, 5.03)0.02 HIV (ITT - Final) (0.86, 3.01)0.13 HIV (per protocol) (1.06, 4.47)0.03 Gonorrhea (0.74, 1.62)0.63 Chlamydia (0.47, 1.08)0.11

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

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

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)

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)

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

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