The main focus of this session was to describe exciting recent advances in drug-eluting intravaginal ring (IVR) technology, using sheep as the pre-clinical animal model. In one variant currently under development, a silicone IVR houses a drug delivery “pod” which can be adapted for a variety of different medications, including ARVs. Data were presented from 4 different studies, evaluating drugs from 4 different ARV classes. Sustained deliveries of tenofovir, saquinavir, raltegravir, and maraviroc (MVC) were demonstrated over 28-days, as determined in cervicovaginal lavage, tissue, and plasma levels. Dual-therapy IVRs with antiretrovirals and hormonal contraceptives are a particularly attractive approach for empowering women to have control over both their sexual and reproductive health. A novel device using polyurethane tubing either permeable to water or with a controlling membrane to titrate specific release rates, was explored with tenofovir alone or in combination with levonorgestrel. In vitro release testing and in vivo tests in sheep (and rabbits) demonstrated the ability to sustain drug concentrations in cervicovaginal fluid and tissue, at high levels over a 90-day period.

Two “other things” were discussed, besides sheep rings. In a model of transmission designed to assess the population-level impact of microbicide use in high prevalence settings, consistent use of a 70% efficacious microbicide by 60% of non-pregnant women was predicted to prevent up to 39% of new infections in women and 11% of new infections in men, over a 10 year period. Up to 10% of mother-to-child transmission cases could be prevented, as well, if HIV is acquired in pregnancy. Expanding the intervention into pregnant women appeared to have a higher overall impact.

Excitement about IVR technology was tempered a bit by negative data on the ability of 2 doses of MVC to prevent rectal SHIV infection, in a macaque study. Six animals received 300mg MVC 24 hours before virus exposure, and another 2 hours thereafter; 4 animals served as controls. Despite overall favorable pharmacokinetics in plasma and rectal secretions similar to those seen in humans, 5 of 6 MVC-treated animals were infected during five rectal SHIV exposures along with 3 of 4 controls. The faster rate of dissociation of MVC from the CCR5 receptor of macaques, compared with humans, may in part explain these findings. Seven-day dosing studies are underway, with explant challenges.