- Assess and compare the safety of vaginal rings (VRs) containing 25 mg dapivirine, 100 mg maraviroc, or the combination of 25 mg dapivirine + 100 mg maraviroc, when used continuously for 28 days by healthy, HIV-uninfected, sexually abstinent women, as compared with the placebo vaginal ring
- Examine the systemic and local pharmacokinetics (PK) of dapivirine and maraviroc in vaginal fluid, plasma and tissue during and after 28 days’ continuous use of a matrix vaginal ring containing 25 mg dapivirine, or 100 mg maraviroc, or 25 mg dapivirine + 100 mg maraviroc
MTN-013/IPM 026 was a Phase 1 safety and PK study of 48 healthy, HIV-uninfected, sexually abstinent, 18-40 years old women. Participants were randomized to receive one of four study VRs (containing 25 mg dapivirine, 100 mg maraviroc, 25 mg dapivirine + 100 mg maraviroc, or placebo) in a 1:1:1:1 ratio. The VR was to be used continuously for approximately 28 consecutive days. Safety assessments were conducted with special consideration for monitoring systemic toxicity and intensive PK assessments were conducted at multiple time points. MTN-013/IPM 026 was the first clinical trial that evaluated a VR containing maraviroc and a VR containing the combination of antiretroviral agents. The design of MTN-013/IPM 026 allowed for a comparison of the safety of each study VR to a placebo VR and provided data regarding the absorption and distribution of the drug(s) administered.
MTN-013 completed follow-up on September 4, 2012. Primary study results were presented at the Conference on Retroviruses and Opportunistic Infections (CROI) held on March 3-6, 2014, in Boston, MA. The primary manuscript was published in Journal of Acquired Immune Deficiency Syndromes on November 1, 2015. A total of five papers have been published from this study.
There was no difference in related genitourinary adverse events between treatment arms compared with placebo. All four study VRs were safe and well-tolerated. Dapivirine was consistently detected in plasma, cervicovaginal fluid (CVF) and cervical tissue; maraviroc was consistently detected only in CVF. Dapivirine levels in cervical tissue were about 10,000-fold higher than in plasma and 10-fold lower than in CVF for both dapivirine only and combination VR study arms. Dapivirine, but not maraviroc, demonstrated concentration-dependent inhibition of HIV-1 infection in cervical tissue.
Multi-site, double-blinded, four-arm, randomized, placebo-controlled trial