SAVVY Vaginal Gel (C31G) for Prevention of HIV Infection: A Randomized Controlled Trial in Nigeria

Abstract

BackgroundThe 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 follow-up visits for HIV testing, adverse event reporting, and study product supply. The study was conducted between September 2004 and December 2006 in Lagos and Ibadan, Nigeria, where we enrolled 2153 HIV-negative women at high risk of HIV infection. Participants were randomized 1∶1 to SAVVY or placebo. The effectiveness endpoint was incidence of HIV infection as indicated by detection of HIV antibodies in oral mucosal transudate (rapid test) or blood (ELISA), and confirmed by Western blot or PCR testing. We observed 33 seroconversions (21 in the SAVVY group, 12 in the placebo group). The Kaplan-Meier estimates of the cumulative probability of HIV infection at 12 months were 0.028 in the SAVVY group and 0.015 in the placebo group (2-sided p-value for the log-rank test of treatment effect 0.121). The point estimate of the hazard ratio was 1.7 for SAVVY versus placebo (95% confidence interval 0.9, 3.5). Because of lower-than-expected HIV incidence, we did not observe the required number of HIV infections (66) for adequate power to detect an effect of SAVVY. Follow-up frequencies of adverse events, reproductive tract adverse events, abnormal pelvic examination findings, chlamydial infections and vaginal infections were similar in the study arms. No serious adverse event was attributable to SAVVY use.Conclusions/SignificanceSAVVY did not reduce the incidence of HIV infection. Although the hazard ratio was higher in the SAVVY than the placebo group, we cannot conclude that there was a harmful treatment effect of SAVVY.Trial RegistrationClinicalTrials.gov NCT00130078

The spread, treatment, and prevention of HIV-1: evolution of a global pandemic

“…Non-vaccine biological interventions designed to prevent infection with HIV-1 after exposure to the virus include topical microbicides. However, multiple first-generation microbicides (nonoxynol-9, cellulose sulphate, and C31G [SAVVY]) have failed to protect in clinical trials (126)(127)(128)(129). Indeed, these early microbicides seemed to increase the risk of infection, perhaps through subclinical irritation of the mucosa.…”

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.…”