Background: Efficacy of the DVR in reducing the risk of HIV-1 infection via vaginal intercourse in HIV-1 uninfected women has been demonstrated in two independent, well-controlled Phase III trials, IPM 027 and MTN-020, conducted in four countries in sub-Saharan Africa. DVR is meant to be used in combination with safer sex practices. The pooled efficacy results of these two trials are presented.
Methods: In the pooled efficacy analysis, HIV-1 infection as measured by HIV-1 seroconversion was the primary endpoint. The efficacy analysis was repeated using the time of first detection of HIV-1 RNA as the endpoint. Adherence to DVR use was defined as ≤23.5 mg of residual dapivirine levels in used rings and dapivirine plasma concentrations of ≥95 pg/mL, measures that indicate at least some DVR use during the prior month.
Results: The rate of HIV-1 seroconversion per 100 person-years was 3.7 (95% CI, 3.1 to 4.3) and 5.0 (95% CI, 4.2 to 5.8) in the dapivirine and placebo ring groups, respectively, resulting in a statistically significant reduction in the risk of HIV-1 infection by 27.4% (95% CI, 8.6 to 42.3%; p=0.0063) relative to placebo. This risk reduction was statistically significantly higher (p=0.026) in participants older than 21 years (39.8%, 95% CI, 20.2 to 54.6%) than in participants 21 years or younger (-4.8%, 95% CI, -57.3 to 30.2). Using time of first detection of HIV-1 RNA, use of the DVR showed a statistically significant reduction in the risk of HIV-1 infection of 29.9% (95% CI, 11.8 to 44.3; p=0.023) relative to placebo. For periods in which participants were defined as adherent to at least some DVR use, HIV-1 infection risk reduction improved to 45.3% (95% CI, 27.4 to 58.8%; p< 0.0001).
Conclusions: The pooled results of two independent well-controlled Phase III trials of DVR, which achieved similar and statistically significant results, resulted in an overall HIV-1 risk reduction of 27.4%. Higher HIV-1 risk reduction was observed with increased adherence to product use. The maximum level of HIV-1 infection risk reduction from vaginal exposure with consistent ring use cannot be determined based on the available data.