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The future role of rectal and vaginal microbicides to prevent HIV infection in heterosexual populations: implications for product development and prevention.

ABSTRACT: To compare the potential impact of rectal (RMB), vaginal (VMB) and bi-compartment (RVMB) (applied vaginally and protective during vaginal and anal intercourse) microbicides to prevent HIV in various heterosexual populations. To understand when a RMB is as useful than a VMB for women practicing anal intercourse (AI).Mathematical model was used to assess the population-level impact (cumulative fraction of new HIV infections prevented (CFP)) of the three different microbicides in various intervention scenarios and prevalence settings. We derived the break-even RMB efficacy required to reduce a female's cumulative risk of HIV infection by the same amount than a VMB.Under optimistic coverage (fast roll-out, 100% uptake), a 50% efficacious VMB used in 75% of sex acts in population without AI may prevent ?33% (27, 42%) new total (men and women combined) HIV infections over 25 years. The 25-year CFP reduces to ?25% (20, 32%) and 17% (13, 23%) if uptake decreases to 75% and 50%, respectively. Similar loss of impact (by 25%-50%) is observed if the same VMB is introduced in populations with 5%-10% AI and for RR(RAI)=4-20. A RMB is as useful as a VMB (ie, break-even) in populations with 5% AI if RR(RAI)=20 and in populations with 15%-20% AI if RR(RAI)=4, independently of adherence as long as it is the same with both products. The 10-year CFP with a RVMB is twofold larger than for a VMB or RMB when AI=10% and RR(RAI)=10.Even low AI frequency can compromise the impact of VMB interventions. RMB and RVMB will be important prevention tools for heterosexual populations.

SUBMITTER: Boily MC

PROVIDER: S-EPMC3332062 | biostudies-literature | 2011 Dec

REPOSITORIES: biostudies-literature

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The future role of rectal and vaginal microbicides to prevent HIV infection in heterosexual populations: implications for product development and prevention.

Boily Marie-Claude MC Dimitrov Dobromir D Abdool Karim Salim S SS Mâsse Benoît B

Sexually transmitted infections 20111201 7

<h4>Objectives</h4>To compare the potential impact of rectal (RMB), vaginal (VMB) and bi-compartment (RVMB) (applied vaginally and protective during vaginal and anal intercourse) microbicides to prevent HIV in various heterosexual populations. To understand when a RMB is as useful than a VMB for women practicing anal intercourse (AI).<h4>Methods</h4>Mathematical model was used to assess the population-level impact (cumulative fraction of new HIV infections prevented (CFP)) of the three different ...[more]

PMID: 22110117

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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

The future role of rectal and vaginal microbicides to prevent HIV infection in heterosexual populations: implications for product development and prevention.

Publications

The future role of rectal and vaginal microbicides to prevent HIV infection in heterosexual populations: implications for product development and prevention.

Similar Datasets

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