BOSTON — A dapivirine vaginal ring was effective for 28 days at blocking HIV infection in cervical tissue, according to data from a first-in-human trial presented here at the 2014 Conference on Retroviruses and Opportunistic Infections.
“What’s very exciting is that the levels of dapivirine found in the cervical tissue were high enough to block HIV infection in the laboratory, with higher levels associated with better protection against HIV,” Beatrice Chen, MD, MPH, assistant professor of obstetrics, gynecology and reproductive sciences at the University of Pittsburgh, said during her presentation. “Unfortunately maraviroc did not have similar success in our trial. However, maraviroc is still a promising drug for a microbicide, if we can develop a ring that produces higher levels of the drug that is better absorbed into the body.”
Chen and colleagues conducted a double-blind, randomized, placebo-controlled trial among 48 sexually abstinent women to evaluate three different vaginal rings containing microbicides: one with dapivirine (International Partnership for Microbicides) only; one with maraviroc (Selzentry, ViiV) only; and one with both dapivirine and maraviroc. The rings included 25 mg dapivirine and/or 100 mg maraviroc. The rings were left in for 28 days and the women underwent cervical biopsies when the rings were removed to determine drug levels and for an HIV explants challenge. The drug levels were also quantified in plasma and vaginal fluid. This study was the first in-human study of a vaginal ring containing maraviroc alone, as well as the first study of a vaginal ring containing two different microbicides.
“We found that the rings were safe in women who used them for 28 days and that women almost always kept them in place throughout the study,” Chen said. “Dapivirine was absorbed well enough among those who had the dapivirine-alone ring, as well as those who had the combination ring.”
Plasma dapivirine levels were similar among women on the dapivirine ring and the combination ring. On day 28, the mean vaginal fluid levels of dapivirine were 14.9 mcg/mL for the dapivirine ring and 10 mcg/mL for the combination ring. The day-28 mean tissue levels of dapivirine were 0.6 mcg/mL for the dapivirine ring and 1.6 mcg/mL for the combination ring.
For maraviroc, the plasma concentrations were below limits of quantification. The day-28 mean maraviroc vaginal fluid levels were 6.7 mcg/mL for the maraviroc ring and 1.1 mcg/mL for the combination ring. Only four women among the maraviroc ring group and the combination ring group had tissue levels of maraviroc above levels of quantification.
“There are currently two very large studies underway in Africa looking at the efficacy of the dapivirine vaginal ring, and our study gives us hope that the ring may be able to prevent HIV infection in these studies,” Chen said.
For more information:
Chen B. Abstract #41. Presented at: CROI 2014. March 3-6, 2014; Boston.
Disclosure: Chen reports no relevant disclosures.