Project Details


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 epithelial 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 microbicide 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 environment of healthy HIV-negative adult women atlow 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 practices, 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 traditional microbicide safety assessments (which are mostly clinical),and will correlate the biomarkers with these traditional 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.Before a microbicide is marketed, its safety will have to be established in special population groups (such as adolescents, pregnant women and high frequency users). These groups are not typically included in standard safety and efficacy trials. In this study, we will characterize these special population groups, with an emphasis on recruitment and retention procedures. Several of the institutions participating in this proposal are involved in clinical testing of candidate microbicides (for example, 0.5% PRO2000/5 gel, TMC120 gel, and perhaps also tenofovir gel) and are likely to be asked to conduct safety studies in these special population groups in the near future. The expected outcomes are recruitmentand retention plans for these special population groups, and a better understanding of sexual and reproductive behaviourin these groups.

In order to study biomarkers, and characterize special population groups for microbicide trials, a strong collaboration between different countries and different disciplines is needed.We need to bring together clinicians, laboratory scientists,social scientists, data staff and administrative staff from institutions in sub-Saharan Africa that are conducting microbicide trials and from institutions in Europe that possess very specific expertise (for example, expertise in cutting edge laboratory techniques). Work Package 1 is designed to maximize collaboration and communication between all of these groups. In the current study, all diagnostic laboratory testing will be done in local laboratories but some cutting edge laboratory testing will be conducted in specialized laboratories in Europe. However, the consortium of scientists on this proposal will decide together which biomarker tests are appropriate for future technology transfer to the African sites. The expected outcome is a technology transfer plan.
Effective start/end date6/04/094/01/13


  • The European & Developing Countries Clinical Trials Partnership : €529,510.00