A vaginal ring that contains dapivirine was "liked" by 93% of adolescent participants in a small U.S. trial of the device that was presented at the 2017 IAS Conference on HIV Science in Paris. Adherence to the study regimen was also quite high, and the device was found to be safe in this population.
Prior studies had shown the ring to be effective in preventing HIV among adult women. The ASPIRE trial in sub-Saharan Africa found up to 75% lower HIV rates among participants who always wore the ring. Protection rates dropped to 56% for consistent users of the device and were even lower for those who wore the device only intermittently. When the results in that trial were stratified by age, researchers found no difference in seroconversion rates between the ring and placebo arms among 18- to 21-year-old women. That age group also showed the lowest adherence.
By contrast, the current study found a 95% adherence rate based on residual drug levels in returned rings. High adherence was also documented by blood plasma samples, which showed that 87% had worn the ring on the day prior to the study visit where the sample was taken. Study presenter Katherine Bunge, M.D., of the University of Pittsburgh and the Microbicides Trial Network attributed this much higher rate of device use to several factors: parental involvement, a relatively short study and carefully chosen participants.
Fewer than 100 young women participated in the study. Since all were between 15 and 17 years old, parental consent was required. That consent was often difficult to obtain, Bunge said, especially since study participants had to be sexually active to be included. If permission were obtained from the parent, that person would have to know that their daughter was having sex. Another issue for parents was the fact that the ASPIRE trial had already shown the device to be effective. What would their daughters gain from participating in this study? Discussions here focused on sexually transmitted infection and HIV testing, as well as related counseling that accompanied the study visits, Bunge explained.
Study participants were randomized to either the dapivirine ring or a placebo ring, with 73 girls using the active ring and 23 the placebo. A new ring was dispensed every four weeks, at which point the used ring was returned. The entire study ran for six months. Blood and vaginal fluid were collected four times during that period, at two, four, 12 and 24 weeks. After three and six months of ring use, participants were asked questions about their experiences and feelings regarding the device. Questions were open-ended to elicit as much detailed information as possible. Researchers also called the girls one week after the beginning and end of the trial to "check in" and address concerns that might have come up.
Another complication related to participants' young age was school. As one of the girls quoted in the related poster presentation put it, "When I was at school ... it would move and then there was no place to like really fix the ring." Some participants reported the ring being displaced or falling out altogether, and more than half said they had taken the device out at least once during one or more months. However, such removals were generally brief.
The majority of participants reported no physical discomfort from using the dapivirine ring, even during sex. The most common concern was that the sex partner might feel the device, even though two-thirds of those who said their partners did feel the ring also reported that it didn't greatly bother them. Most partners reacted positively to the ring. "Well, my boyfriend likes the ring more than using a condom," said one girl. Participants also considered the ring to be more reliable than condoms. As one of them put it: "You can, um, you can forget condoms; you can forget the diaphragm; but the ring is in you thirty days."
Other concerns included increased vaginal discharge and odor, and occasional cramps. Girls were also concerned about hygiene when wearing the ring during menstruation. "I feel like that's kind of gross to have like, blood on the ring," said one. Participants had been advised that it would be better not to use tampons during the study, and some found that to be "frustrating." There were ten product holds, but none of them were related to use of the device. Most of the discontinuations were due to pregnancy or pelvic inflammatory disease.
Local groups are applying to license the dapivirine ring in adult women in Europe, the United States and South Africa. "HIV doesn’t distinguish between a 16-year-old and an 18-year-old," noted Sharon Hillier, Ph.D., of the University of Pittsburgh in a related press release. If the ring is approved for adults, safety data are needed to get regulatory approval for teenagers, she added. Obtaining that data was the primary goal of the current study, according to Bunge.
The next step is the REACH trial, which will compare oral pre-exposure prophylaxis with the dapivirine ring in 16- to 21-year-old women in sub-Saharan Africa. It is expected to start in late 2017.