SAVVY® (C31G) Gel for Prevention of HIV infection in Women: A Phase 3, Double-Blind, Randomized, Placebo-Controlled Trial in Ghana
ABSTRACT The 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.
This 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.
SAVVY 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.
Full-textDOI: · Available from: Baafuor Opoku, Jun 27, 2015
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ABSTRACT: Abstract To assess the views of potential end-users of a microbicide in KwaZulu-Natal regarding the characteristics that would justify further development, three focus group discussions were conducted in 2009 with 23 local staff members working on a microbicide clinical trial, 20 former trial participants and 14 Community Advisory Board members not enrolled in the trial, in an area with high HIV incidence and low consistent condom use. All participants agreed on the need for additional HIV prevention options that are as effective as possible and can be used by women. The majority of respondents stated that even a highly acceptable HIV prevention option with protection as low as 30% would still be an important addition to condoms for women; that a partially protective microbicide would have to be introduced as part of the existing prevention messages in order to continue promoting condom use; that there should eventually be a choice between antiretroviral (ARV) and non-ARV-based microbicides and a choice of how and where to access microbicides. Respondents also felt it would be important to make plans for access to a microbicide that can offer protection, even if partial, rather than wait to find out if alternative microbicides are equally or more effective. Potential end-users in a high HIV prevalence area believe that a partially effective microbicide would be an important addition to the limited HIV prevention options for women. The significant challenges of introducing a partially protective HIV prevention option were recognised, but seen as ones worth facing, as well as an opportunity to lay the ground work for the introduction of more efficacious HIV prevention methods in the future.AIDS Care 09/2012; 25(5). DOI:10.1080/09540121.2012.722604 · 1.60 Impact Factor
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ABSTRACT: Abstract Sexual transmission of HIV is the major cause of spread of HIV in Africa and the Third World and is an unmet medical need. Recently, microbicides have attracted attention because they allow females to protect themselves and their offspring. We are exploiting one of the four retroviral enzymes, the ribonuclease H, RNase H, as a novel approach for a microbicide. It is the only enzyme of HIV not yet targeted by antiretroviral therapy. The enzyme is linked to the reverse transcriptase (RT) and hydrolyzes the RNA moiety of RNA-DNA hybrids. The RNase H is located inside virus particles and normally functions during viral replication inside cells. Here we show that activating the RNase H prematurely inside the virus particles destroys the viral genome and abrogates viral infectivity. The antiviral compound consists of a synthetic oligodeoxynucleotide (ODN), which creates an artificial RNA-DNA hybrid substrate for the RNase H inside the particle. The compound was analyzed in mouse models including humanized SCID mice and the vagina of mice. Infection was reduced up to 1000-fold or could be completely prevented. The compound is suitable as microbicide or to prevent mother-to-child transmission.AIDS research and human retroviruses 08/2012; DOI:10.1089/aid.2012.0067 · 2.46 Impact Factor
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