Use of the dapivirine vaginal ring for pre-exposure prophylaxis (PrEP) does not lead to resistance mutations in women who seroconvert, Urvi Parikh, Ph.D., with the University of Pittsburgh, reported at the HIV Research for Prevention 2018 conference in Madrid, Spain. Dapivirine is an investigative non-nucleoside reverse transcriptase inhibitor (NNRTI) that is being evaluated only for HIV prevention.
Data for this study come from the phase III ASPIRE trial, which tested the safety and effectiveness of the ring in Southern Africa. Its 2,629 participants were randomly assigned to the study device or a placebo, and 168 of them seroconverted during the study period (median follow-up: 1.6 years).
A woman using the dapivirine ring could get drug-resistant HIV in the following scenarios, Parikh explained in a press conference:
- She is already living with HIV when she starts to use the ring.
- She continues to use the ring after seroconverting.
- She acquires HIV that is already resistant to dapivirine.
All ASPIRE participants were tested for HIV prior to entering the study and then monthly thereafter, and the ring was discontinued immediately in anyone who seroconverted. Standard genotyping tests were run on the plasma from all seroconverters to check for specific mutations in the virus. In addition, plasma from a subset of 58 women in the dapivirine arm and 57 matched controls in the placebo arm was tested using highly sensitive next-generation sequencing. This research-only method detects genetic changes in thousands of individual viruses inside the body and identifies resistance present in as little as 1% of a person's viruses.
No dapivirine-specific mutations were detected, nor were any rare mutations that may confer resistance to the study drug. Thirteen women had mutations indicating resistance to NNRTIs, but five of them were in the placebo group and thus had never been exposed to dapivirine. The observed NNRTI resistance likely came from these women's particular HIV virus, not from using the dapivirine ring, Parikh noted.
In contrast to oral PrEP, the dapivirine in the ring stays mostly in the vagina. "But should any HIV pass the drug barrier in the vagina and start multiplying in the bloodstream, there probably isn't enough dapivirine circulating to be noticed and to cause resistant virus to emerge," she explained [[in a press release from the Microbicide Trials Network https://medicalxpress.com/news/2018-10-sensitive-drug-resistance-dapivirine.html]], the study's sponsor.
"The findings suggest the risk that drug resistance could develop with the use of the dapivirine ring is minimal," she concluded.