Abstract
ObjectiveThe objective of this trial was to determine the effectiveness of 1.0% C31G (SAVVY) in preventing male-to-female vaginal transmission of HIV infection among women at high risk.Methodology/Principal FindingsThis was a Phase 3, double-blind, randomized, placebo-controlled trial. Participants made up to 12 monthly visits for HIV testing, adverse event reporting, and study product supply. The study was conducted between March 2004 and February 2006 in Accra and Kumasi, Ghana. We enrolled 2142 HIV-negative women at high risk of HIV infection, and randomized them to SAVVY or placebo gel. Main outcome measures were the incidence of HIV-1 and HIV-2 infection as determined by detection of HIV antibodies from oral mucosal transudate specimens and adverse events. We accrued 790 person-years of follow-up in the SAVVY group and 772 person-years in the placebo group. No clinically significant differences in the overall frequency of adverse events, abnormal pelvic examination findings, or abnormal laboratory results were seen between treatment groups. However, more participants in the SAVVY group reported reproductive tract adverse events than in the placebo group (13.0% versus 9.4%). Seventeen HIV seroconversions occurred; eight in participants randomized to SAVVY and nine in participants receiving placebo. The Kaplan-Meier estimates of the cumulative probability of HIV infection through 12 months were 0.010 in the SAVVY group and 0.011 in the placebo group (p = 0.731), with a hazard ratio (SAVVY versus placebo) of 0.88 (95% confidence interval 0.33, 2.27). Because of a lower-than-expected HIV incidence, we were unable to achieve the required number of HIV infections (66) to obtain the desired study power.Conclusions/SignificanceSAVVY was not associated with increased adverse events overall, but was associated with higher reporting of reproductive adverse events. Our data are insufficient to conclude whether SAVVY is effective at preventing HIV infection relative to placebo.Trial RegistrationClinicalTrials.gov NCT00129532
Highlights
Topical microbicides are designed to inhibit the sexual transmission of Human Immunodeficiency Virus (HIV) and other disease pathogens
In post hoc analyses that examined subgroups defined by selfreported frequency of gel use, we found a greater treatment group difference in the incidence of reported reproductive system and breast disorders (17.3 per 100 person-years in the SAVVY group and 10.1 per 100 person-years in the placebo group) among the subgroup of participants whose self-reported gel use was at or below the overall median than among the subgroup of participants whose self-reported gel use was above the overall medium
Lower-than-expected HIV incidence has been an increasing problem in HIV prevention trials and the lower-than-expected HIV incidence seen in this trial may have been due in part at least 3 factors: 1) a greater-than-expected effect of trial risk reduction measures such as condom use, 2) participants who join clinical trials may be more inclined to safer behavior than those in their community who do not participate, and 3) an inaccurate estimate of trial incidence due to changes in the local epidemic
Summary
Topical microbicides are designed to inhibit the sexual transmission of Human Immunodeficiency Virus (HIV) and other disease pathogens. They offer a female-controlled prophylactic option in situations where male condom use cannot be negotiated. No clinical studies have yet demonstrated that these products can prevent HIV infection, and spermicides with the surfactant nonoxynol-9 (N-9) have caused mucosal erosion and ulceration, which may increase the risk of HIV transmission [2,3,4]. We investigated the safety and effectiveness of 1.0% SAVVY in preventing HIV infection in a population of young, sexually active women at high risk for acquiring HIV infection
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