A vaginal ring containing dapivirine, a non-nucleoside reverse transcriptase inhibitor (NNRTI), was safe and effective in preventing HIV-1 infection in African women. Among women who acquired HIV-1 infection during the ASPIRE study conducted by the Microbicide Trials Network (MTN-020), NNRTI resistance associated mutations were detected in both dapivirine ring and placebo ring recipients with no significant difference between arms. NNRTI-based antiretroviral therapy (ART) remains the first-line standard of care in many regions of the world. The impact of dapivirine ring use at the time of HIV-1 acquisition on the subsequent response to NNRTI-containing ART is unknown.
The virologic failure rate following initiation of ART was assessed among women who acquired HIV-1 infection during participation in MTN-020, a randomized, placebo-controlled trial of a monthly dapivirine vaginal ring. Virologic failure was defined as lack of suppression of plasma HIV-1 RNA to <200 copies/ml by 6 months after ART initiation or viral rebound to ≥200 copies/ml after initial suppression at any time.
Among 168 participants with incident HIV-1 infection during dapivirine or placebo ring use in MTN-020, 158 (94%; 65 dapivirine, 93 placebo) had at least 1 follow-up visit, of whom 78 (49%) initiated NNRTI-containing ART during follow-up (29 dapivirine, 49 placebo). The median time from estimated HIV-1 seroconversion to ART initiation was 10.3 months. The median time from ART initiation to HIV-1 RNA <200 copies/ml was approximately 90 days for both dapivirine and placebo ring recipients. The Cox proportional hazards model estimate for the likelihood of virologic suppression between the dapivirine ring and placebo ring arms was 1.0 (95% confidence interval 0.6-1.6). Among 57 women with at least 6 months of post-ART follow-up, 10 (17.5%) experienced virologic failure, 6/36 (16.7%) placebo ring recipients and 4/21 (19%) dapivirine ring recipients (P=0.82).
Compared to placebo, we observed no difference in the time to virologic suppression or the risk of virologic failure for women who had received the dapivirine vaginal ring and then initiated NNRTI-containing ART. These results provide reassurance that standard WHO-recommended ART regimens are effective in the setting of breakthrough HIV-1 infection in women who had received the dapivirine vaginal ring, although continued monitoring of viorologic response is warranted.