BOSTON — Two studies presented here at CROI 2016 suggest that preventive use of vaginal rings containing dapivirine could safely reduce the incidence of new HIV transmissions to women.
Although the ring provided overall protection of approximately 30% in both trials, younger women participating in the trial more often demonstrated new transmissions, higher levels of drug remaining in used rings and low drug plasma concentrations, the researchers reported.
“Today, we have two trials demonstrating statistically significant reductions in HIV incidence in women, a population where previous trials have had flat results, and that’s a big step forward,” Jared M. Baeten, MD, PhD, professor of global health, medicine, epidemiology and biostatistics at the University of Washington, said during a press event. “What we need to understand now is what — in the best-case use — HIV prevention [the ring] can provide, as well as the populations who would use a pill, and who are the populations who would not use a pill but might use a ring.”
Jared M. Baeten
Efficacy appears to increase with greater adherence
In the MTN-020/ASPIRE study, Baeten and colleagues enrolled women aged 18 to 45 years from 15 sites in Malawi, Uganda, Zimbabwe and South Africa. An equal number of participants randomly received either a monthly ring containing 25 mg of the non-nucleoside reverse transcriptase inhibitor dapivirine, or placebo. The women returned for monthly follow-up visits to receive a new self-administered ring, receive testing for HIV and STD, and report any adverse events. In addition, researchers examined adherence to the intervention on a quarterly basis by measuring levels of the drug in participants’ serum and, after the first year of the trial, measuring residual drug levels in used rings. The study’s primary endpoints were the incidence of HIV transmission and serious adverse events.
The final analysis included 2,629 women (median age, 26 years; 41% married). Seventeen percent reported more than one partner in the 3 months before the study’s initiation, and 64% reported that their primary partner was aware of the vaginal ring.
Participants attended 91% of expected monthly visits, with a median follow-up of 1.6 years. Plasma samples meeting the cutoff dapivirine concentration were detected in 82% of samples, and 84% of returned rings contained less than 23.5 mg of the study drug. The researchers observed no significant differences in primary safety endpoints between study groups.
There were 71 HIV infections among women assigned the dapivirine ring (3.3 per 100 person-years) vs. 97 infections among those given placebo (4.5 per 100 person-years). Although this translated to a 27% relative reduction (95% CI, 1%-46%), removing two sites with exceptionally low adherence increased the reduction to 37% (95% CI, 12%-56%). Changes in efficacy were seen based on age, with a 61% efficacy (95% CI, 32%-77%) among women aged 25 years or older compared with a –27% efficacy (95% CI, –133% to 31%) among women aged 18 to 21 years. Outcomes among these age groups mirrored trends in adherence levels, leading Baeten and colleagues to suggest a potential relationship between these two variables.
“HIV was reduced by one-third overall, and by more than half among a subgroup of women who appeared to use the ring better,” Baeten said. “This is the first demonstration of a sustained-release approach for antiretroviral prevention, and HIV protection in this study, not surprisingly, was greater with greater adherence.”
Older women demonstrate superior protection, adherence
These results were comparable to those reported by Annalene Nel, MD, PhD, of the International Partnership for Microbicides in South Africa, and the researchers of the IPM 027/The Ring Study.
In this multicenter, randomized trial, 1,959 women recruited at centers in South Africa and Uganda were randomly assigned to receive monthly dapivirine rings at a 2:1 ratio. The participants were aged 18 to 45 years (median age, 25 years; 91% unmarried).
In an analysis that included 2,805 person-years of follow-up, Nel and colleagues identified an incidence of 4.08 new infections per 100 person-years in those assigned the intervention. When compared with the 6.1 per 100 person-years incidence rate seen among those assigned placebo, the intervention demonstrated a 30.7% reduction in HIV infection (95% CI, 0.9%-51.5%). Similar to the ASPIRE study, greater efficacy was observed among women older than 21 years, and among women with lower residual drug levels in used rings. The incidence of adverse events was similar between study arms.
“Women in sub-Saharan Africa remain at very high risk of HIV despite the rollout of HIV treatment and male circumcision,” Nel said during the press event. “That is unacceptable for us. Today’s results give us hope that we must, and can, do better.” – by Dave Muoio
Baeten JM, et al. Abstract 109LB. Presented at: Conference on Retroviruses and Opportunistic Infections; Feb. 22-25, 2016; Boston.
Baeten JM, et al. New Engl J Med. 2016;doi:10.1056/NEJMoa1506110.
Nel A, et al. Abstract 110LB. Presented at: Conference on Retroviruses and Opportunistic Infections; Feb. 22-25, 2016; Boston.
Disclosures: Baeten and Nel report no relevant financial disclosures. Please see the full studies for a list of all other authors’ relevant financial disclosures.