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Higher Adherence Tied to 65% Protection With Dapivirine Vaginal Ring
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21st International AIDS Conference (AIDS 2016), July 18-22, 2016, Durban, South Africa
IAC: Residual dapivirine ring levels indicate higher adherence to vaginal ring is associated with HIV-1 protection ......."Results suggest ring use is associated with at least 56% and potentially >75% protection when used consistently" - (07/22/14)
Mark Mascolini
Estimating adherence by measuring residual dapivirine left in returned vaginal rings, MTN-020/ASPIRE researchers figured that higher adherence led to a 65% reduction in HIV risk compared with placebo among women in four southern African countries [1].
Initial analysis of MTN-020/ASPIRE, a 2629-woman double-blind placebo-controlled trial, determined that using vaginal rings loaded with the nonnucleoside dapivirine trimmed the risk of HIV acquisition 27% (P = 0.046) in an intention-to-treat analysis [2]. The protection rate rose to 37% when the investigators excluded two study sites with lower adherence or retention. But the dapivirine ring offered no protection to women 21 or younger, who had lower adherence.
Trial participants were asked to make monthly visits at which they got tested for HIV, returned their current ring, and got a new ring. Starting 12 months after the study began, returned rings were sent to a central lab to measure residual dapivirine levels. Dapivirine rings initially contained 25 mg of the nonnucleoside. MTN investigators figured that a returned ring still containing 23.5 mg or more dapivirine indicated nonadherence, less than 23.5 mg indicated low to high adherence, and less than 22 mg indicated medium to high adherence They rated adherence of each woman by determining residual dapivirine levels in rings returned in the previous 3 months. In women with follow-up from study month 12 and beyond, a time-varying Cox model adjusted for age and study site compared HIV acquisition with dapivirine versus placebo according to dapivirine level.
This analysis included 2359 women with 1089 person-years of follow-up in the placebo arm, 360 person-years in the nonadherent group, 741 person-years in the low to high adherence group, and 458 person-years in the medium to high adherence group. HIV incidence stood at 4.6 per 100 person-years in the placebo arm, 3.6 per 100 in the nonadherent arm, 1.9 per 100 in the low to high adherence group, and 1.5 per 100 in the medium to high adherence group. Compared with placebo, dapivirine-nonadherent women had a nonsignificant 31% HIV risk reduction (P = 0.24). But compared with placebo, women with low to high dapivirine ring adherence had a significant 56% risk reduction (P = 0.007) and women with medium to high dapivirine ring adherence had a significant 65% risk reduction (P = 0.01).
The same adherence analysis suggested medium to high dapivirine ring adherence cut HIV risk 72% in women older than 21 (95% confidence interval 21 to 90) and 50% in women 21 or younger (nonsignificant with 95% confidence interval -78 to 86). Other analyses divided women assigned to dapivirine into four groups according to how long a woman had the ring: no use and bottom, middle, and top use groups. These analyses generally indicated that longer dapivirine ring use conferred higher levels of protection from HIV--up to 75% in the top-use group-- compared with placebo.
The MTN-020/ASPIRE investigators concluded that "across multiple analyses, there is a statistically significant relationship between ring use and HIV protection." They proposed that these analyses suggest a dose-response relationship between ring use and HIV risk, with risk reduction ranging from at least 56% to as high as 75% with consistent use.
References
1. Brown E, Palanee-Philips T, Marzinke M, et al. Residual dapivirine ring levels indicate higher adherence to vaginal ring is associated with HIV-1 protection. 21st International AIDS Conference (AIDS 2016). July 18-22, 2016. Durban, South Africa. Abstract TUAC0105LB.
2. Microbicide Trials Network. MTN-020 questions and answers.
http://www.mtnstopshiv.org/news/studies/mtn020/qa
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