1. Current MC Related Research Rakai Health Sciences Program(RHSP) Uganda WHO Country Update Meeting Arusha- June 8-10, 2010 Adrian M Musiige (MBChB/MPH) MC Trainer / Coordinator Rakai Community Cohort Study

2. Running MC related grants • Community Effects of MC on HIV Epidemic with Nested Clinical Research • HIV, STIs, and behaviors in a RCT & post-Trial Surveillance • In Situ analysis of HIV transmission in foreskin & • HPV Testing Supplements • Genital anaerobes, inflammation and HIV risk, Rakai

3. Rakai District; South Western Uganda Rakai Cohort Annual Surveillance N=15000 Age 15-49 A community hub where men are seen for their post trial follow up visits

4. Community Effects of MC on HIV Epidemic with Nested Clinical Research • Post Trial community Surveillance • Acceptance, Behavior, HIV Acquisition/Transmission • Impact at Individual & Population level • Relevant Clinical Research • Healing by HIV status • Surgical stress on HIV viral load • HIV shedding from surgical wound • Foreskin Inflammation and mucosal Immunology studies • Mucosal Barriers and susceptibility to HIV • Mucosal Immunological and inflammatory characteristics in HIV- men with and without HIV exposure

5. Sexual Behavior in Post trial surveillance(interim analyses) Number of sex partners during the trial (years 1-2) and during post-trial surveillance (years 3-4), by circumcision status Condom use during the trial (years 1-2) and post-trial surveillance (years 3-4) by circumcision status

6. HIV, STIs, and behaviors in the trial and post trial • Long term follow up • Effectiveness of Circ on HIV/STI prevention • Effect of Circ on sexual behaviors • MC and STI Prevention • STI assays on stored trial samples

7. HIV, STIs, and Behaviors in the RCT & post-RCT Surveillance Transmission in the foreskin supplement • Earliest events and virus-host cell interactions in HIV transmission • New HIV Sero-positive • New PCR+ but Sero-negative • To determine basis for low F M transmission using foreskin studies of HIV- men in discordant relationships n=50

8. HIV, STIs, and Behaviors in the RCT & post-RCT Surveillance HPV testing supplement To assess efficacy of MC for HR HPV prevention in HIV+ and HIV- men To assess efficacy of MC in preventing HR HPV in female partners of HIV+ and HIV- men

9. MC and STI; recent findings

10. Genital anaerobes, inflammation and HIV risk, Rakai • Correlation between the burden of genital anaerobes and inflammatory markers in HIV uninfected men and their female partners • Association Genital anaerobes, Inflammatory markers and risk of HIV acquisition/transmission • Estimate role of genital anaerobes and inflammation in the efficacy of MC

11. Foreskin Surface area and HIV acquisition in Rakai, Uganda (Size Matters) Kigozi G et al. AIDS: 23 Oct 2009 - Volume 23 - Issue 16 - p 2209-2213 Preparing the prepuce for storage Focal Inflammation in the Foreskin (left) and densities of CD4 and CD8 cells (lower panel) n NMDS plot of penile microbiota before surgery and at follow up post surgery

12. Summary Studies on Long term efficacy of MC Community level effectiveness of MC on HIV/STI prevention Effect of MC on sexual behavior Mucosal Immunological studies The potential mediating role of genital micro-biota and inflammation in efficacy of MC

13. ACKNOWLEDGEMENT • Research Grants • NIAID • Bill & Melinda Gates Foundation • Circumcision Service & Provider Training • PEPFAR