Pod-intravaginal rings offered complete protection from new SHIV infections in macaques.
Findings from a recent study suggest that 2 antiretroviral drugs can provide protection against HIV transmission through an intravaginal ring (IVR).
The 2 drugs, tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC), were delivered by sustained release IVR to successfully prevent new SHIV162p3 infections in female pigtailed macaques for over 4 months, according to a study published by PLOS ONE.
"We are extremely pleased with the results of this study," said researcher Marc M. Baum, PhD. "The observed protection in macaques indicates the significant potential for the TDF-FTC drug combination delivered via the pod-IVR to successfully prevent sexual HIV infection in humans."
Every 2 weeks, 6 monkeys received pod-IVRs that contain 65-mg of TDF and 68-mg of FTC. There was also a control group that did not receive any treatment. After 1 week, all monkeys received 1 of 16 vaginal exposures to a SIV/HIV virus that infects monkeys, 50 TCID50 of SHIV162p3, according to the study.
During the 18-week study, the rings were changed every 2 weeks. Researchers discovered that 100% of monkeys treated with pod-IVRs had protection from the virus compared with 0% of the control group that did not receive the pod-IVR.
These pigtailed macaques are good models to use since they have similar menstrual cycles, vaginal architecture, and vaginal microbiome, according to the study.
"This model has been used extensively to evaluate several lead candidates for preexposure prophylaxis (PrEP) against HIV. We are able to critically evaluate the pharmacokinetics, safety, and efficacy of PrEP candidates in ways that are not feasible in humans, thereby allowing us to make informed decisions on candidates in the PrEP pipeline prior to initiation of costly clinical trials,” Dr Baum said. "Up to this point, topical preexposure prophylaxis (PrEP) against HIV has been marginally successful in recent clinical trials with low adherence rates being a primary factor for failure.
“Our hypothesis has been that controlled, sustained release of ARV [antiretroviral] drug combinations could overcome these low adherence rates if the product itself could remain protective for extended periods of time. This study has shown that the drug combination and the versatile drug delivery system that we have designed can indeed remain protective for over four and a half months."
The pod-IVRs have the ability to lessen nonadherence and side effects since the drugs are absorbed in a steady dose.
"In contrast to daily therapies, sustained release approaches to drug delivery have special appeal for use in the developing world: they are less expensive on a per-patient, per-day basis, they require less infrastructure to provide to the community, and they can be more effective," Dr Baum said.
The only FDA-approved antiretroviral drug for HIV PrEP is an oral combination of TDF and FTC, according to the study.
"The novel and versatile drug delivery system that our team is developing has proven that it has the capacity to deliver and maintain protective levels of multiple drugs," Dr Baum concluded. "Protection against (S)HIV virus that was observed in this study warrants clinical evaluation of the pod-IVR design and the sustained delivery of a variety of AVRs to find the best combination possible."