Vaginal gels containing the anti-retroviral drug tenofovir seemed promising at first in preventing HIV infection, but failed during trials because of poor delivery. Now an intra-vaginal ring that slowly dispenses the drug has been shown effective in controlling simian immunodeficiency virus (SHIV) in macaque monkeys. The TDF-IVR (tenofovir disoproxil fumarate intravaginal ring) has shown complete control in preventing SHIV transmission over a four month period with monthly ring changes. All the monkeys that had the ring and were exposed to the virus remained SHIV negative, while the control group was essentially completely infected.
The next step is to test the safety of the ring in an initial clinical trial on human subjects. 60 women will participate in the study, which will last 14 days, but the true effectiveness of the ring in humans will be tested only after the safety phase is complete.
Here we describe a reservoir IVR technology that delivers the tenofovir prodrug tenofovir disoproxil fumarate (TDF) continuously over 28 d. With four monthly ring changes in this repeated challenge model, TDF IVRs generated reproducible and protective drug levels. All TDF IVR-treated macaques (n = 6) remained seronegative and simian-HIV RNA negative after 16 weekly vaginal exposures to 50 tissue culture infectious dose SHIV162p3. In contrast, 11/12 control macaques became infected, with a median of four exposures assuming an eclipse of 7 d from infection to virus RNA detection. Protection was associated with tenofovir levels in vaginal fluid [mean 1.8 × 105 ng/mL (range 1.1 × 104 to 6.6 × 105 ng/mL)] and ex vivo antiviral activity of cervicovaginal lavage samples. These observations support further advancement of TDF IVRs as well as the concept that extended duration drug delivery devices delivering topical antiretrovirals could be effective tools in preventing the sexual transmission of HIV in humans.
Study in Proceedings of The National Academy of Sciences: Intravaginal ring eluting tenofovir disoproxil fumarate completely protects macaques from multiple vaginal simian-HIV challenges.
Northwestern University: Study: New Medical Device Extremely Effective at Preventing Immunodeficiency Virus…
