SAVVY® (C31G) Gel for Prevention of HIV infection in Women: A Phase 3, Double-Blind, Randomized, Placebo-Controlled Trial in Ghana

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

Candidate Microbicide PPCM Blocks Human Immunodeficiency Virus Type 1 Infection in Cell and Tissue Cultures and Prevents Genital Herpes in a Murine Model

“…The premature closure of several narrow-spectrum-microbicide human clinical trials underscores the challenges in microbicide development. The increase in HIV infection among women using nonoxynol-9 (N-9), Savvy (33), or cellulose sulfate highlights the need for improved preclinical evaluation of both the safety and the efficacy of candidate microbicides (15,41). Specifically, efficacy studies must include a more extensive evaluation of the activities of candidate drugs against HIV isolates representing multiple clades in cell and explant culture systems reflective of the genital tract.…”

Simian-Human Immunodeficiency Viruses and Their Impact on Non-Human Primate Models for AIDS

“…This poorly understood process cannot be properly evaluated in vitro. The recent failure and enhanced transmission observed in the first microbicide efficacy trials with nonoxynol-9 and Savvy [193,194] warrant the need for controlled and careful investigation of topical products in animal models. A phase II/III trial with nonoxynol-9, an over the counter spermicide, in a vaginal gel formulation increased the risk of acquisition of HIV among users of the gel [195].…”

Lessons learnt from implementing an empirically informed recruitment approach for FEM-PrEP, a large HIV prevention clinical trial

“…Such populations, however, can be challenging to identify and recruit into clinical trials. Recruitment approaches reported most often in pre-exposure prophylaxis (PrEP), vaginal microbicide, and HIV vaccine clinical trials include recruiting from community venues such as markets, education institutions, bars, and hotels/hostels; [1][2][3][4][5][6][7] from health facilities such as family planning, sexually transmitted infection (STI), and primary care clinics; [4][5][6][7][8][9][10][11] through peer recruiters; 6,9,11 and through strategies combining geography and sexual network characteristics.…”

“…We began planning for FEM-PrEP soon after the completion of the SAVVY trials in West Africa, also sponsored by FHI 360. 1,2 Investigators from these trials reported that they were unable to determine the effectiveness of the study product because of lower than expected HIV incidence within the study population. With this in mind, and building upon FHI 360's previous PrEP clinical trial formative research, we conducted formative research in three of the four FEM-PrEP sites (Bondo, Pretoria, and Arusha) to inform the FEM-PrEP recruitment strategy by identifying places where HIV incidence might be high.…”