1. AN INTERNATIONAL MULTI-CENTRE, RANDOMISED, DOUBLE- BLIND, PLACEBO-CONTROLLED TRIAL TO EVALUATE THE EFFICACY AND SAFETY OF 0.5% AND 2% PRO 2000 GELS FOR THE PREVENTION OF VAGINALLY ACQUIRED HIV INFECTION FUNDED BY UK MRC AND DFID TRIAL RESULTS DECEMBER 2009 MDP 301

2. OBJECTIVE The primary objective of the trial is to determine the efficacy and safety of 0.5% & 2% PRO 2000 gel compared to placebo gel in preventing vaginally acquired HIV infection

3. MDP 301 STUDY SITES AFRICA Tanzania Zambia South Africa Uganda Uganda: Masaka MasakaTanzania: Mwanza MwanzaZambia: Mazabuka Mazabuka South Africa: Mtubatuba Mtubatuba Durban Durban Johannesburg Johannesburg

4. STUDY DESIGN All participants received HIV counseling and testing, free condoms, and diagnosis and treatment of curable STIs HIV-negative, sexually active, non-pregnant women, 16y or older (18y in SA and Zambia) Placebo + Condoms PRO 2000 0.5% + Condoms Phase III Clinical Trial PRO 2000 2% + Condoms

5. OVERVIEW OF PARTICIPANTS Screened N = 15818 Not Eligible for Trial N = 5359 At Screening N = 4766 Pregnant at Screening N = 331 HIV positive at screening N = 4103 At Enrolment N = 593 Pregnant at Enrolment N = 57 Ineligible for Other Reason N = 536 Enrolled N = 9385 (19 enrolled twice) 2% PRO 2000 N =2734 0.5% PRO 2000 N = 3326 Placebo N = 3325

6. MDP 301 RETENTION Retention rates based on person years of follow up Retention rate censored for pregnancy % Retention rate not censored for pregnancy % Week 1293%94% Week 2490%92% Week 4087%90% Week 5284%88%

7. N(%) Gel Use Overall 1 N (%) Gel Use With Condom 2 N (%) Gel Use in Unprotected Sex Acts 3 Week 4 (N=5833)5352 (91%)3472 (59%)1880 / 2035 (92%) Week 24 (N=4805)4367 (91%)3012 (63%)1355 / 1465 (92%) Week 40 (N=4482)4116 (92%)2906 (65%)1210 / 1319 (92%) Week 52 (N=4644)4096 (88%)2873 (62%)1223 / 1389 (88%) MDP 301 ADHERENCE (excluding women on 2%) 1 Gel used at last sex act with or without a condom. 2 Gel and condom used at last sex act 3 Gel used when last sex was without condom: ( n gel use / n unprotected sex acts) (%)

8. 0.5% PRO 2000Placebo HIV Cases130123 Women years28732836 Incidence per 100wy 95% CI 4.5 (3.8, 5.4) 4.3 (3.6, 5.2) Hazard Ratio1.05 95% CI(0.82, 1.34) P-value0.712 PRIMARY EFFICACY ANALYSIS - HIV-1 INFECTION BY ARM - COMPARISON There were two modifications to a classic intention to treat analysis for the main analysis Women were censored when they stopped gel for pregnancy HIV seroconversions beyond the visit window for week 52 were excluded

9. 2% PRO 2000 (n=2591) 0.5% PRO 2000 (n=2587) Placebo (n=2543) HIV Cases8267 Woman years174117321717 Incidence per 100wy (95% CI) 4.7 (3.8, 5.8) 3.9 (3.0, 4.9) 3.9 (3.1, 5.0) Hazard ratio (95% CI) 1.21 (0.88, 1.68) 0.99 (0.70, 1.39) 1.00 p-value0.2390.940- NB: 2% discontinued on 14 th February 2008. HIV-1 INFECTION BY ARM FEBRUARY 2008

10. Conclusion There was no significant difference in the rate of HIV infection between 0.5% PRO 2000 and placebo. There was no significant difference in the rate of HIV infection between 2% PRO 2000 and placebo. There was no significant difference in the safety markers between 0.5% PRO 2000 and placebo. There was no significant difference in the safety markers between 2% PRO 2000 and placebo.

11. KEY MESSAGES Women and their partners liked the gel and used it The study teams made supreme efforts to remind women about their appointments and the women came Therefore the participants and staff gave PRO 2000 the best chance, and it is disappointing that the gel did not add benefit to the HIV prevention package The study benefited women: regular exams, STI testing and treatment, risk reduction and supportive counseling Male and Female condoms remain the most suitable option for HIV prevention

12. What’s Next MDP 301 and previous microbicide trials strongly support the concept, as women do use the products We hope the ARV microbicides, which are much more potent in the laboratory, will prove to be effective in the two clinical trials that are ongoing The results from PrEP research with oral ARV are also eagerly awaited eg. Tenofovir & Truvada Infrastructure is there and ready for the next trials The microbicide field should not lose hope of finding a women initiated product for HIV prevention

13. ACKNOWLEDGEMENTS Participants and their partners Trial communities Research teams IRBs and Regulatory agencies at each participating site Trial Steering Committee and Independent Data Monitoring Committee Donors: Department for International Development (DFID) and UK Medical Research Council Commercial partner o Indevus/Endo

14. MDP Partnership

15. Dissemination in clinical trial communities National and provincial stakeholders Clinical trial staff Local stakeholders Participants Unblinding Community members Future dissemination plans

16. Reactions HIV education Communication skills Increase in condom use Empowerment Action Community recognition High quality service

17. Participant Quote “Even if the gel may prove not effective, we played a role in the fight against HIV. We learnt about caring for ourselves – like screening for cervical cancer and using condoms. This research taught us a lot: we even learnt to encourage others to test for HIV and we gained confidence of helping those already infected”.