Topical Antiretroviral Drug Combination Blocks HIV Transmission

Combination antiretroviral drugs delivered from Pod-Intravaginal Rings (pod-IVR) were found to successfully prevent (S)HIV infection.

During a 6-month study published in PLOS One, 6 macaques were given pod-IVRs that contained 65-mg of tenofovir disoproxil fumarate (TDF) and 68-mg of emtricitabine (FTC) every 2 weeks with a total of 8 ring changes. A week after the insertion of the first pod-IVR, the macaques received the first of 16 vaginal exposures to 50 TCID50 of SHIV162p3.

The results of the study found that at week 18, all 6 macaques with TDF-FTC pod-IVRs achieved complete protection, compared with 0 of 9 control animals.

“We are extremely pleased with the results of this study,” said researcher Marc M. Baum. “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.

“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.”

The new delivery system can remain protective for more than 4-and-a-half months, and can help overcome the low adherence rate of topical PrEP.

Additionally, the approach also helps eliminate several challenges related to the oral administration of these drugs. Since the drugs are continually released into the vaginal tissue, it can help with patient adherence to a regular dosing schedule.

Furthermore, the delivery system decreases side effects.

“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,” Baum said. “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.

“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.”