ArticlesEffectiveness of COL-1492, a nonoxynol-9 vaginal gel, on HIV-1 transmission in female sex workers: a randomised controlled trial
Introduction
Although the male condom, when used consistently and correctly, provides high levels of protection against HIV-1 and other sexually transmitted infections, negotiating its use is not always feasible for many women. Therefore, there is need for a female-controlled method for prevention of HIV-1. Research on microbicides is part of this global effort.
The product that has been tested most is the spermicide nonoxynol-9 (recommended international name nonoxinol-9), which shows in-vitro activity against HIV-1 and other sexually transmitted infections1, 2, 3, 4, 5 and can prevent simian immunodeficiency virus infection in macaques.6 Results of several studies in women showed that nonoxynol-9 had a protective effect against Neisseria gonorrhoeae and Chlamydia trachomatis infection.7, 8, 9, 10
At the time we planned our study, data for HIV-1 prevention were conflicting. Although results of an observational study in female sex workers in Cameroon showed a protective effect in more consistent spermicide users than less consistent users (relative risk 0·1; 95% Cl 0·1–0·6),11 results of a randomised placebo-controlled trial did not show a significant protective effect (1·6; 0·8–2·8).12 The high number of toxic effects seen in this study was thought to be attributable to the high dose of nonoxynol-9—ie, 1000 mg, with about 50% of this dose bioavailable.
Because nonoxynol-9 is readily available, low in price, and has been on the US market as an over-the-counter product since the 1960s, we thought controversy surrounding the drug as a potential HIV-1-prevention method needed to be resolved. We decided to study a new gel formulation with a low nonoxynol-9 dose (52·5 mg), COL-1492, which covers the cervix and the vaginal walls and gives immediate availability of the drug. Because of the known dose-dependent effect of this drug,13 the absence of any local toxic effects of the gel was documented first in women in developed countries, then by a study of the phase 3 target population.14, 15 Results of both trials showed no difference between nonoxynol-9 and placebo with respect to frequency of lesions.
Our aim was to compare the effectiveness of nonoxynol-9 with placebo gel in prevention of HIV-1 infection in HIV-1-negative female sex workers.
Section snippets
Participants
Between September, 1996, and June, 2000, we did a randomised, placebo-controlled, triple-blind trial, in which we screened healthy, HIV-l-negative female sex workers in South Africa (Durban and Johannesburg), Thailand (Bangkok and Hat Yai), Benin (Cotonou), and Côte d'lvoire (Abidjan) for inclusion in our study. Women were recruited from clinics for sexually transmitted infection in Bangkok, Hat Yai, and Johannesburg; from clinics for female sex workers in Cotonou and Abidjan; and in Durban
Results
2146 women were screened and 1005 were enrolled. A total of 892 women (excluding 113 from Johannesburg) were randomly allocated (figure), of whom 127 had no HIV-1 test after enrolment. These women were excluded from the primary analysis, which thus included 765 women. 563 women completed the study, including 57 women with a follow-up visit within 6 weeks before the end of study enrolment. 37 women withdrew during the study (figure).
The overall retention rate of participants in the study was 71%
Discussion
Our results show that nonoxynol-9 increased risk of HIV-1 infection compared with placebo. Risk was especially high in women who used the study drug gel more than 3·5 times per day and who also had a high incidence of lesions with epithelial disruption. This finding suggests that nonoxynol-9 has an adverse effect on vaginal integrity when used frequently, thus increasing women's susceptibility to HIV-1 infection. At low frequency use, nonoxynol-9 had no effect, either positive or negative, on
References (19)
- et al.
Inactivation of HTLV-III/LAV-infected cultures of normal human lymphocytes by nonoxynol-9 in vitro
Lancet
(1985) - et al.
In-vitro inactivation of HIV-1 by contraceptive sponge containing nonoxynol-9
Lancet
(1988) - et al.
The effect of contraceptives containing nonoxynol-9 on the genital transmission of simian immunodeficiency virus in rhesus macaques
Fertil Steril
(1992) - et al.
Use of nonoxynol-9 and reduction in rate of gonococcal and chlamydial cervical infections
Lancet
(1992) - et al.
Inhibition of growth of Chlamydia trachomatis by nonoxynol-9 in vitro
Antimicrob Agents Cliemotlhr
(1985) - et al.
The efficacy of nonoxynol-9 from an in vitro point of view
AIDS
(1996) - et al.
In vitro activity of the spermicide nonoxynol-9 against Clilamydia trachoniatis
Antimicrob Agents Chemother
(1985) - et al.
A clinical trial of nonoxynol-9 for preventing gonococcal and chlamydial infections
J Infect Dis
(1988) - et al.
Microbicides, meta-analysis, and the N-9 question: where's the research?
Sex Transm Dis
(1998)
Cited by (714)
ZB-06, a vaginal film containing an engineered human contraceptive antibody (HC4-N), demonstrates safety and efficacy in a phase 1 postcoital test and safety study
2023, American Journal of Obstetrics and GynecologyHIV/AIDS Prevention
2023, Manson's Tropical Diseases, Fourth EditionThe use of PSA as a biomarker of recent semen exposure in female reproductive health studies
2021, Journal of Reproductive ImmunologyWomen-specific routes of administration for drugs: A critical overview
2021, Advanced Drug Delivery Reviews
Study group members listed at end of report