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Rectal microbicide development.

ABSTRACT: Individuals practicing unprotected receptive anal intercourse are at particularly high risk of HIV infection. Men who have sex with men (MSM) in the developed and developing world continue to have disproportionate and increasing levels of HIV infection. The past few years have seen important progress in demonstrating the efficacy of oral pre-exposure prophylaxis (PrEP), vaginal microbicides, and treatment as prevention, but there has also been significant progress in the development of rectal microbicides. The purpose of this review is to summarize the status of rectal microbicide research and to identify opportunities, challenges, and future directions in this important field of HIV prevention.Recent phase 1 rectal microbicide studies have characterized the safety, acceptability, compartmental pharmacokinetics, and pharmacodynamics of both UC781 and tenofovir gels. The tenofovir gel formulation used in vaginal studies was not well tolerated in the rectum and newer rectal-specific formulations have been developed and evaluated in phase 1 studies.Complex phase 1 studies have provided important data on candidate rectal microbicides. Tenofovir gel is poised to move into phase 2 evaluation and it is possible that a phase 2B/3 effectiveness study could be initiated in the next 2-3 years.

SUBMITTER: McGowan I

PROVIDER: S-EPMC3861872 | biostudies-literature | 2012 Nov

REPOSITORIES: biostudies-literature

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Rectal microbicide development.

McGowan Ian I

Current opinion in HIV and AIDS 20121101 6

<h4>Purpose of review</h4>Individuals practicing unprotected receptive anal intercourse are at particularly high risk of HIV infection. Men who have sex with men (MSM) in the developed and developing world continue to have disproportionate and increasing levels of HIV infection. The past few years have seen important progress in demonstrating the efficacy of oral pre-exposure prophylaxis (PrEP), vaginal microbicides, and treatment as prevention, but there has also been significant progress in th ...[more]

PMID: 23032732

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Project description:Preexposure prophylaxis (PrEP) of HIV infection with tenofovir-containing regimens is effective, but plagued by poor adherence in some studies. Options for safe, effective, and acceptable PrEP products, especially for men and women at risk of HIV via receptive anal intercourse (RAI), are needed. We performed a randomized, partially blinded, first-in-human evaluation of four candidate rectal microbicide vehicles-aqueous gel, aqueous fluid, lipid gel, and lipid fluid-to select a prototype for further clinical development. Eight seronegative participants received three doses of each product with each dose separated by at least 2 weeks: one dose was given alone without simulated RAI in clinic, another dose was followed by simulated RAI in clinic, and another dose was self-administered at home in the context of RAI with a partner. Assessments included safety, acceptability, colon histology, ex vivo HIV infectivity of colon tissue explants, and colonic luminal distribution of vehicle and HIV surrogates. Adverse events were all mild and mainly sigmoidoscopy associated. There were minor differences in colon distribution of products and little effect of RAI. Vehicle distribution covered 95% (±7% standard deviation) of the distribution of an HIV surrogate in the colonic lumen. The lipid fluid vehicle increased HIV colon tissue infectability 5-fold [log10 p24 0.68 (95% confidence interval 0.08, 1.28)] and aqueous gel provided 6-fold protection [log10 p24 0.80 (95% confidence interval 0.20, 1.41)] compared to no product baseline. Colon permeability of lipid vehicles was more than 10-fold greater than aqueous vehicles. All products received similar acceptability ratings, though trends favored the gel products. Intensive simultaneous assessment of safety and toxicity, luminal and tissue distribution, ex vivo HIV infectivity, and product acceptability in relevant sexual contexts provided clear differentiation among candidate gels very early in product development. We selected the aqueous gel for further development as a rectal microbicide vehicle.

Dataset Information

Rectal microbicide development.

Publications

Rectal microbicide development.

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