EFFECTS OF SEXUAL ACTIVITY ON IMMUNE ACTIVATION AMONG HIV- EXPOSED SERONEGATIVE FEMALES AT PUMWANI CLINIC, NAIROBI Abel Onyango, PhD student Kenya AIDS Vaccine Initiative-University of Nairobi Dept. of Medical Microbiology

OUTLINE  Background  Problem statement  Justification  Research questions  Hypothesis  Objectives  Methods  Time-plan

OVERALL OBJECTIVE To determine the effects of sex work on systemic T cell activation in HIV-Exposed Seronegative (HESN) female sex workers at Pumwani Clinic, Nairobi

4 BACKGROUND In Kenya, new infections =104,137 (91,000=Adults) Sexual transmission accounts for approx. 93% of new HIV infections; with heterosexual bearing 77% cases About 10-15% population resist HIV (Shearer and Clerici, 2010)

NEW HIV INFECTIONS-KENYA 2011

6 HESN FEMALE SEX WORKERS Definition: Previous =3 or more years Current definition >7yrs of follow up with normal CD4 and seronegative and PCR result for HIV

7 MODEL OF THE SEROCONVERSION Fowke et al., 1996

8 CHARACTERISTICS OF HESN Lower levels of activated T cells in the peripheral blood Increased levels of peripheral regulatory T cells Decreased levels of inflammatory cytokine production

PROBLEM STATEMENT Global vision for ‘zero new infections’ by 2015 heightens need for effective preventive HIV and treatment strategies Sexual transmission is the primary driver of Kenya’s HIV infections 9

10 JUSTIFICATION  Varying susceptibility to HIV between high risk individuals has not been clearly elucidated  Role of menstrual cycle on immune activation is unclear  Urgent need for prevention strategies and/or new treatment options

11 RESEARCH QUESTIONS Does persistent sex-driven stimulation induce Immune Quiescent state among HESN female sex workers? What effect does menstrual cycle have upon immune activation among HESN female sex workers during abstinence?

HYPOTHESIS HESN individuals downregulate sex work- driven immune activation more efficiently than HIV susceptible controls, which provides protection against subsequent HIV exposure

METHODOLOGY Sex work-Abstinence-Sex work Data analysis Data analysis HESN N = 40 HIV-Neg N = 40 HIV-Pos N = 40 Consent and recruitment Base-line blood draws Longitudinal observed study Blood draws and lab analysis Blood CD69, CD38, CCR5,CCR7,HLA-DR levels Blood draws and lab analysis Blood CD69, CD38, CCR5,CCR7,HLA-DR levels Data analysis Analysis will be done using paired T-test and ANOVA to compare differences in means of T cell activation determinants Data analysis Analysis will be done using paired T-test and ANOVA to compare differences in means of T cell activation determinants

FLOW CYTOMETRY PANEL CD3 PECy5 CD4 FITC CD8 V500 CCR7 PE-CF594 CD45RA Alexa700 CCR5 V450 HLA-DR APC-H7 CD161 APC CD95 PE, CD69 PE-Cy7

15 SO WHAT??? Clear understanding and potential discovery of unique protective mechanisms among HESN individuals may provide opportunity for further scientific knowledge and perhaps develop new preventive interventions or treatment options for HIV

ACKNOWLEDGEMENTS Dr. Keith Fowke,PhD Prof. Omu Anzala, MD, PhD Dr. Julius Oyugi, PhD Julie Lajoie,PhD Genevieve Boily- Larouche,PhD Lyle McKinnon,PhD UOM IDRC UNITID staffs KAVI-UON staffs