The dapivirine vaginal ring reduced the rate of new HIV-1 infection by 31% in a phase III clinical trial involving 1,959 high-risk women in sub-Saharan Africa, according to a report published in the New England Journal of Medicine.
The dapivirine-containing ring is replaced every month and was used in this study for up to 2 years. It was not associated with any safety concerns, said Annalene Nel, MD, PhD, of the International Partnership for Microbicides, Silver Spring, Md., and her associates.
The International Partnership for Microbicides is a nonprofit group that developed the ring, which can be self-inserted and removed and which provides a sustained release of the antiretroviral drug for at least 4 weeks. QPharma of Malmö, Sweden, manufactures the rings and donated the ones used in this study, but was not otherwise involved in the trial.
The study participants were sexually active women aged 18-45 years (mean age, 26) treated at seven research centers in South Africa and Uganda. Almost all of them (98%) had only one male sexual partner. For the purposes of this trial, the women were asked to attend the participating clinics every 4 weeks to have the rings replaced and to provide a plasma sample. This allowed the researchers to measure the residual amount of dapivirine in the used rings and to measure plasma levels of the drug, both of which were indicators of compliance.
A total of 1,307 women were randomly assigned to receive dapivirine rings and 652 to receive placebo rings. At the data cutoff point, 615 women (31.4%) were still in the trial and 761 (38.8%) had completed it; 583 women (29.8%) had discontinued early. All the participants at one medical center were withdrawn by the sponsor because of high rates of protocol violation at that facility and corresponding high rates of patient nonadherence with the device.
The primary efficacy endpoint – the rate of HIV-1 seroconversion during follow-up – was 4.1 per 100 person-years with the dapivirine ring, compared with 6.1 per 100 person-years with the placebo ring. This represents a 31% lower infection rate with the active treatment (hazard ratio, 0.69). A subgroup analysis that excluded participants at the protocol-violating facility showed a seroconversion rate of 3.6 per 100 person-years with the active treatment vs. 5.4 per 100 person-years with the placebo, a 30% reduction in the infection rate, the investigators said ().
The findings were consistent across other subgroup analyses, including those that categorized the participants according to their adherence levels, as measured by plasma levels and residual ring levels of dapivirine.
The cumulative incidence of adverse events was similar between the two study groups (87.4% and 85.7%, respectively), as was the incidence of grade 3 or 4 adverse events. None of the more serious adverse events were judged to be related to the devices. Mild product-related adverse events occurred in 5 women (0.4%) in the dapivirine group and 3 (0.5%) in the placebo group. There also were no significant differences between the two study groups in the incidence of laboratory abnormalities, rates of sexually transmitted and other genital infections, or pregnancy rates.
The study was funded by the International Partnership for Microbicides, which is supported by the Bill and Melinda Gates Foundation, Irish Aid, the Ministry of Foreign Affairs of Denmark, the Ministry of Foreign Affairs of the Netherlands, the Norwegian Agency for Development Cooperation, the U.K. Department for International Development, the U.S. Agency for International Development, and the President’s Emergency Plan for AIDS Relief.
Dr. Nel reported having no relevant financial disclosures; one of her associates reported ties to Janssen and Johnson & Johnson.