Dataset Information

Microbicides for HIV prevention.

ABSTRACT: Although the HIV incidence rate has slowed in some countries, HIV remains a serious health challenge, particularly in the developing world. The epidemic is increasingly feminised, with young women at high risk of acquiring the virus. There is thus a clear requirement for acceptable woman-initiated methods of HIV prevention. Foremost among these are vaginally-applied substances known as microbicides; early research into potential microbicides focussed on non-HIV-specific compounds such as surfactants and polyanionic entry inhibitors. However, proof of the microbicide concept as a viable prevention strategy was not provided until the CAPRISA 004 trial of a microbicide containing the HIV-specific antiretroviral tenofovir was completed in mid-2010. Confirmation of the proof of concept provided by CAPRISA 004 by at least two major trials will hopefully lead to licensure of the product by 2018. Parallel studies are planned to ascertain the feasibility of implementation of these products in the public sector with subsequent research focussed on appropriate and acceptable methods of delivery of the active ingredient, and to increase adherence through other delivery systems such as vaginal rings.

SUBMITTER: Ramjee G

PROVIDER: S-EPMC3284101 | biostudies-other | 2011 Dec

REPOSITORIES: biostudies-other

ACCESS DATA

Publications

Microbicides for HIV prevention.

Ramjee Gita G

The Indian journal of medical research 20111201 6

Although the HIV incidence rate has slowed in some countries, HIV remains a serious health challenge, particularly in the developing world. The epidemic is increasingly feminised, with young women at high risk of acquiring the virus. There is thus a clear requirement for acceptable woman-initiated methods of HIV prevention. Foremost among these are vaginally-applied substances known as microbicides; early research into potential microbicides focussed on non-HIV-specific compounds such as surfact ...[more]

PMID: 22310825

Similar Datasets

Project description:UNLABELLED:Vaginal HIV microbicides offer great promise in preventing HIV transmission, but failures of phase 3 clinical trials, in which microbicide-treated subjects had an increased risk of HIV transmission, raised concerns about endpoints used to evaluate microbicide safety. A possible explanation for the increased transmission risk is that the agents shifted the vaginal bacterial community, resulting in loss of natural protection and enhanced HIV transmission susceptibility. We characterized vaginal microbiota, using pyrosequencing of bar-coded 16S rRNA gene fragments, in samples from 35 healthy, sexually abstinent female volunteer subjects (ages 18 to 50 years) with regular menses in a repeat phase 1 study of twice-daily application over 13.5 days of 1 of 3 gel products: a hydroxyethylcellulose (HEC)-based "universal" placebo (10 subjects), 6% cellulose sulfate (CS; 13 subjects), and 4% nonoxynol-9 (N-9; 12 subjects). We used mixed effects models inferred using Bayesian Markov chain Monte Carlo methods, which showed that treatment with active agents shifted the microbiota toward a community type lacking significant numbers of Lactobacillus spp. and dominated by strict anaerobes. This state of the vaginal microbiota was associated with a low or intermediate Nugent score and was not identical to bacterial vaginosis, an HIV transmission risk factor. The placebo arm contained a higher proportion of communities dominated by Lactobacillus spp., particularly L. crispatus, throughout treatment. The data suggest that molecular evaluation of microbicide effects on vaginal microbiota may be a critical endpoint that should be incorporated in early clinical assessment of microbicide candidates. IMPORTANCE:Despite large prevention efforts, HIV transmission and acquisition rates remain unacceptably high. In developing countries, transmission mainly occurs through heterosexual intercourse, where women are significantly more vulnerable to infection than men. Vaginal microbicides are considered to be one of the most promising female-controlled products, in that women themselves insert the microbicides into the vagina to prevent HIV transmission during sexual intercourse. The failure of several microbicides in clinical trials has raised questions concerning the low in vivo efficacy of such anti-HIV molecules. This study was designed to gain insights into the failures of two microbicides by testing the hypothesis that the microbicides negatively affect a critical line of defense against HIV, the vaginal microbiota. The results suggest that in the early assessment of candidate microbicides, culture-independent evaluation of their effect on the vaginal microbiota should be considered and may constitute a critical endpoint.

Dataset Information

Microbicides for HIV prevention.

Publications

Microbicides for HIV prevention.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets