abel onyango, phd student kenya aids vaccine initiative-university of nairobi

EFFECTS OF SEXUAL ACTIVITY ON IMMUNE ACTIVATION AMONG HIV-EXPOSED SERONEGATIVE FEMALES AT PUMWANI CLINIC, NAIROBI

Abel Onyango, PhD studentKenya AIDS Vaccine Initiative-University

of NairobiDept. of Medical Microbiology

OUTLINE

BackgroundProblem statementJustificationResearch questionsHypothesisObjectivesMethodsTime-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

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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

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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

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MODEL OF THE SEROCONVERSION

Fowke et al., 1996

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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

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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

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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

HESNN = 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

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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