Safety and tolerability of the ring, a secondary endpoint, was similar among the groups, with slightly more than one-fourth of participants in each arm having a mild adverse event, most commonly associated with abnormal vaginal discharge or menstrual irregularities such as spotting.
The investigators also looked at endogenous progesterone levels as a surrogate for ovulation. Although the ring’s package insert recommends to start using it within the first 5 days after the start of menses, the median enrollment time was 9 days after menses in all groups. Nonetheless, all participants in the control and atazanavir groups had undetectable progesterone values (less than 5 ng/mL) by day 14.
In contrast, among women in the efavirenz group, all women had undetectable progesterone values only at day 21.
The findings suggest that, when considering contraception and ART in HIV-infected women, developers of intravaginally administered drugs should consider systemic drug-drug interactions, because hormones released from a vaginal ring are extensively absorbed and act systemically. It is also important to consider local drug-drug interactions with the microbiome, because although it is known that dapivirine released from a vaginal ring can concentrate in the vaginal tract, possible interactions with the local microbiome, local drug transporters, and local drug-metabolizing enzymes are not known, Dr. Scarsi cautioned.
The study was supported by the National Institutes of Health. Merck provided the vaginal ring used in the study. Dr. Scarsi reported having no conflicts of interest to disclose.
SOURCE: Scarsi KK et al.