ObjectivesSuccessful control of the HIV/AIDS pandemic requires reduction of HIV-1 transmission at sexually-exposed mucosae. No prevention studies of the higher-risk rectal compartment exist. We report the first-in-field Phase 1 trial of a rectally-applied, vaginally-formulated microbicide gel with the RT-inhibitor UC781 measuring clinical and mucosal safety, acceptability and plasma drug levels. A first-in-Phase 1 assessment of preliminary pharmacodynamics was included by measuring changes in ex vivo HIV-1 suppression in rectal biopsy tissue after exposure to product in vivo.MethodsHIV-1 seronegative, sexually-abstinent men and women (N = 36) were randomized in a double-blind, placebo-controlled trial comparing UC781 gel at two concentrations (0.1%, 0.25%) with placebo gel (1∶1∶1). Baseline, single-dose exposure and a separate, 7-day at-home dosing were assessed. Safety and acceptability were primary endpoints. Changes in colorectal mucosal markers and UC781 plasma drug levels were secondary endpoints; ex vivo biopsy infectibility was an ancillary endpoint.ResultsAll 36 subjects enrolled completed the 7–14 week trial (100% retention) including 3 flexible sigmoidoscopies, each with 28 biopsies (14 at 10 cm; 14 at 30 cm). There were 81 Grade 1 adverse events (AEs) and 8 Grade 2; no Grade 3, 4 or procedure-related AEs were reported. Acceptability was high, including likelihood of future use. No changes in mucosal immunoinflammatory markers were identified. Plasma levels of UC781 were not detected. Ex vivo infection of biopsies using two titers of HIV-1BaL showed marked suppression of p24 in tissues exposed in vivo to 0.25% UC781; strong trends of suppression were seen with the lower 0.1% UC781 concentration.ConclusionsSingle and 7-day topical rectal exposure to both concentrations of UC781 were safe with no significant AEs, high acceptability, no detected plasma drug levels and no significant mucosal changes. Ex vivo biopsy infections demonstrated marked suppression of HIV infectibility, identifying a potential early biomarker of efficacy. (Registered at ClinicalTrials.gov; #NCT00408538)

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OBJECTIVES. The purpose of the study was to determine the contraceptive efficacy of the female condom and to provide data about the device to the US Food and Drug Administration. METHODS. The clinical trial was conducted at six US sites and three sites in Latin America. Eligible subjects were in mutually monogamous relationships and agreed to use the female condom as their only means of contraception for 6 months. RESULTS. A total of 328 subjects contributed to the analysis of contraceptive efficacy. Twenty-two US subjects and 17 Latin American subjects became pregnant, yielding 6-month gross cumulative accidental pregnancy rates of 12.4 and 22.2, respectively. During perfect (consistent and correct) use of the method, the 6-month accidental pregnancy rates were 2.6 and 9.5 for the US and Latin American centers, respectively. There were no serious adverse events related to the use of the method. CONCLUSIONS. The female condom provides contraceptive efficacy in the same range as other barrier methods, particularly when used consistently and correctly, and has the added advantage of helping protect against sexually transmitted diseases.

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