Characterisation of novel microbicide safety biomarkers in East and South Africa

Vaginal microbicides are being developed to expand HIV prevention options for women and couples. A healthy vaginal environment protects women from infections and should therefore remain intact during and after product administration. Up to recently, microbicide safety trials included naked-eye pelvic exams and colposcopy to visualize genital epithelial disruption and inflammation and vaginal fluid microscopy to evaluate the vaginal flora. However, recent experiences with the candidate microbicide cellulose sulfate gel suggest that these measurements are insufficient to predict harm. Since then , some research groups have started to include biomarkers of genital inflammation and epthelial integrity, and have started to enumerate HIV target cells, in human safety trials. However, normative value ranges of these biomarkers have not yet been established in population groups that are relevant for microbicde trials, and many additional potential biomarkers have not yet been evaluated. We propose to characterize biomarkers of inflammation, epithelial integrity, immune activation and antimicrobial activity in the cervicovaginal encironment of healthy HIV-negaive adult women at low risk for HIV, healthy HIV-negative adult women at high risk for HIV, HIV-negative adult women with BV, HIV-negative adult women using traditional vaginal pratices. HIV-negative adult pregnant women, HIV-negative adolescents, healthy HIV-positive adult women, and microbicide and placebo gel users (the latter using stored specimens) in kenya, Rwanda, Tanzania and South Africa. We will also conduct tradional assessments. The expected outcomes are the identification of promising biomarkers that could be introduced in the next generation of microbicide safety trials, and baseline data on these biomarkers against which future assessments in women who are using candidate microbicide products can be compared.