The Dapivirine vaginal ring empowers women by giving them a device that they can use to protect themselves from HIV infection and which in no way requires agreement or permission from their male partner/s. Two landmark studies were presented at CROI. Adherence had always been the problem seen in previous studies of similar technologies.
MTN 020/ Aspire Study
This was a placebo controlled RTC. 2629 <50% married women from 4 African countries were randomised to two arms - one was the Dapivirine containing ring the other was a placebo ring. Dapivirine is an nnrti. The median age of the women was 26 - ranging from 18 to 45. The ring is replaced every four weeks and meant to be in situ all of the time.
Adherence was assessed by measuring blood levels - levels >95 pg/ml was consistent with > 8 hrs of use. 82% of plasma samples were at this level or greater. Adherence would be over estimated if the ring was inserted > 8 hrs prior to the clinic visit. Returned rings were also assessed for residual drug. 84% were found t have levels < 23.5 suggesting adequate compliance.
median followup was 1.6 years. Women attended 91% of expected visits.
Overall there was a 37% reduction in expected HIV infections in the women on the active treatment arm. Interestingly in women <21 years of there was NO reduction in infections and in women above 21 years there was a 51% reduction in expected infections. Analysis suggested poor adherence in women < 21 yrs of age.
The rings were well tolerated in both arms with essentially no significant adverse events.
The Ring Study IPM 027
This was an RCT double blinded trial studying the safety and efficacy of a Dapivirine vaginal ring. 1959 women from two African countries were randomised 2:1 Dapivirine ring and placebo. The women aged 18 - 45 received HIv prevention counselling. Adherence was objectively assessed by plasma levels throughout the trial and measurement of residual drug in returned rings. Rings were replaced every 4 weeks. The study concluded end 2015 after most women had been tudied for two years. All women will be offered an active ring at the first visit after conclusion of the study.
Expected HIV infections were reduced by 31% in the group using the active ring.
The study organisers concluded that the ring was safe and well tolerated with an overall reduction of 31%. They noted that was a high incidence of HIV infection in the group studied of 8 % per year.
These number do not sound that great to me. However they do compare pretty well to the IPPREX findings presented in 2011 re oral Truvada as PrEP. It may be that adherence would be much better in an open label situation with better levels of education and understanding about the importance of always having the ring in situ no matter what else is happening. So that as we see in community settings adherence is much better and the protection against infection almost absolute.