Design: Randomized, double-masked, placebo-controlled phase 3 trial.
Setting: Postnatal and family planning clinics of the Queen Elizabeth Central Hospital and two health centers in¬†Blantyre, Malawi.
Participants:¬†Nonpregnant¬†HIV-uninfected and -infected women.
Intervention:¬†Intravaginal¬†metronidazole¬†treatment and placebo gels provided at baseline and every 3¬†mo¬†for 1 y.
Outcome measures: Primary: Cross-sectional and longitudinal comparisons of BV frequency at baseline, 1¬†mo¬†after product dispensation (post-treatment evaluation [PTE]), and every quarterly visit. Secondary: Effect of treatment on BV clearance and recurrence.
Results: Baseline: 842 HIV-uninfected and 844 HIV-infected women were enrolled. The frequency of BV at baseline in treatment and placebo arms, respectively, was 45.9% and 46.8% among HIV-uninfected women, and 60.5% and 56.9% among HIV-infected women. Primary outcomes: At the¬†PTEs¬†the prevalence of BV was consistently lower in treatment than placebo arms irrespective of HIV status. The differences were statistically significant mainly in HIV-uninfected women. Prevalence of BV was also reduced over time in both treatment and placebo arms. In a multivariable analysis that controlled for other covariates, the effect of¬†intravaginal¬†metronidazole¬†treatment gel compared with placebo was not substantial: adjusted relative risk (RR) 0.90, 95% confidence interval (CI) 0.83‚Äì0.97 in HIV-uninfected women and adjusted RR 0.95, 95% CI 0.89‚Äì1.01 in HIV-infected women. Secondary outcomes:¬†Intravaginal¬†metronidazole¬†treatment gel significantly increased BV clearance (adjusted hazard ratio [HR] 1.34, 95% CI 1.07‚Äì1.67 among HIV-uninfected women and adjusted HR 1.29, 95% CI 1.06‚Äì1.58 among HIV-infected women) but was not associated with decreased BV recurrence.¬†Safety:¬†No serious adverse events were related to use of¬†intravaginal¬†gels.
Conclusion: Intermittent microbicide treatment with intravaginal gels is an innovative approach that can reduce the frequency of vaginal infections such as BV.