Jared Baeten and Zeda Rosenberg at CROI 2018. Photo by Liz Highleyman.
Two parallel open-label studies of the dapivirine vaginal ring released interim results at the 25th Conference on Retroviruses and Opportunistic Infections (CROI 2018) on Wednesday. They indicate that women used the ring more consistently than in the earlier randomised studies and as a result the ring was more effective in preventing HIV infections. The ring stopped more than half of the HIV infections that would otherwise have occurred.
The ring, which is similar to devices used for contraception, is designed to be worn inside the vagina for a month at a time; women can insert and remove it themselves.
The two studies, HOPE (MTN 025) and DREAM (IPM 032), are open-label extensions of the two randomised, placebo-controlled studies of the vaginal ring known as ASPIRE (MTN 020) and the Ring Study (IPM 027). These two studies previously reported effectiveness of 27% and 31% respectively.
These two open-label studies are very similar, recruiting women in countries in southern and eastern Africa who had taken part in the previous randomised studies. Participants know they are receiving an active product and that it has proven to be effective and safe.
The HOPE study enrolled 1407 participants with an average age of 31, while DREAM enrolled 900 participants with an average age of 29. A significant proportion had sexually transmitted infections when recruited to the studies: 16% and 18% respectively. Recruitment and retention has generally been good.
Adherence appears to be higher than in the randomised studies. Adherence is estimated by measuring drug levels in the rings that are returned after use. This indicates that 89.5% and 96% of women in HOPE and DREAM had used the ring at least some of the time in the previous month. This compares to 77% and 83% in the randomised studies.
As the open-label studies do not have placebo arms (a comparison group that does not receive the intervention), effectiveness cannot be directly measured. Nonetheless, the researchers would expect HIV incidence in the two cohorts to be 4.1% and 3.9% respectively. In fact, it was 1.9% and 1.8% in the two studies, each indicating an effectiveness of 54%.
Jared Baeten of the Microbicide Trials Network made a comparison with oral pre-exposure prophylaxis (PrEP). In the original iPrEx study of PrEP, effectiveness had only been 44%, but it was 50% in its open-label extension and 100% in people who took four or more doses a week. Further studies and demonstration projects were needed to demonstrate PrEP’s extremely high efficacy in circumstances where adherence was high.
The vaginal ring studies have essentially started the second stage of this process, Baeten said. The final results will be released next year and will stratify users by adherence, relating adherence to efficacy rates.