Rakai Health Sciences Program(RHSP)

UgandaWHO Country Update Meeting

Arusha- June 8-10, 2010

Adrian M Musiige (MBChB/MPH)

MC Trainer / Coordinator Rakai Community Cohort Study

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

A community hub where men are seen for their post trial follow up visits

Rakai District; South Western Uganda

Rakai CohortAnnual SurveillanceN=15000 Age 15-49

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

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

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

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

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

Effect of MC Reference

HR HPV in (-)Men

Decreased AcquisitionIncreased Clearance

Ronald H Gray et al. J Infect Dis 2010 Apr. 6

HR HPV in (+)Men

Reduced Prevalence and Incidence of 12/14 HR genotypes

David Serwadda et al. AIDS 2010 Mar 13; 24(5): 787

HSV2Significantly reduced cumulative probability of infection, 28% Efficacy

Aaron A R Tobian et al. Lancet 2009- Jul.18; 374(9685): 229-37

Syphilis No effect

Bacterial Vaginosis

Decreased significantlyRonald H Gray et al.Am J Obstet and Gynecol 2009 Jan; 200(1): 42 e1-42. e7

T. Vaginalis Decreased Significantly

Role of GUD & HSV2 reduction in MC efficacy

Only 19% of the protection

MC and STI; recent findings

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

Focal Inflammation in the Foreskin (left) and densities of CD4 and CD8 cells (lower panel)

Preparing the prepuce for storage

n NMDS plot of penile microbiota before surgery and at follow up post surgery

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

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

Research Grants•NIAID

•Bill & Melinda Gates Foundation

Circumcision Service & Provider Training

•PEPFAR