Journal Article

Topical Delivery of Tenofovir Disoproxil Fumarate and Emtricitabine from Pod-Intravaginal Rings Protects Macaques from Multiple SHIV Exposures

McNicholl, Janet M., Miller, Christine S., Mitchell, James M., Zhang, Jining, Fanter, Rob, Gunawardana, Manjula, Smith, James M., Churchman, Scott A., Smith, Thomas J., Yang, Flora, Baum, Marc M., Dinh, Chuong T., Butkyavichene, Irina, Moss, John A., Srinivasan, Priya

2016

Overview

Topical preexposure prophylaxis (PrEP) against HIV has been marginally successful in recent clinical trials with low adherence rates being a primary factor for failure. Controlled, sustained release of antiretroviral (ARV) drugs may help overcome these low adherence rates if the product is protective for extended periods of time. The oral combination of tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) is currently the only FDA-approved ARV drug for HIV PrEP. A novel pod-intravaginal ring (IVR) delivering TDF and FTC at independently controlled rates was evaluated for efficacy at preventing SHIV162p3 infection in a rigorous, repeat low-dose vaginal exposure model using normally cycling female pigtailed macaques. Six macaques received pod-IVRs containing TDF (65 mg) and FTC (68 mg) every two weeks, and weekly vaginal exposures to 50 TCID50 of SHIV162p3 began one week after the first pod-IVR insertion. All pod-IVR-treated macaques were fully protected throughout the study (P = 0.0002, Log-rank test), whereas all control animals became infected with a median of 4 exposures to infection. The topical, sustained release of TDF and FTC from the pod-IVR maintained protective drug levels in macaques over four months of virus exposures. This novel and versatile delivery system has the capacity to deliver and maintain protective levels of multiple drugs and the protection observed here warrants clinical evaluation of this pod-IVR design.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Acquired immune deficiency syndrome / Administration, Intravaginal / Administration, Topical / AIDS / Animals / Antiretroviral agents / Antiretroviral drugs / Biology and life sciences / Chlamydia trachomatis / Clinical trials / Condoms / Contraceptive Devices, Female / Controlled release / Disease prevention / Disease transmission / Drug delivery / Drug delivery systems / Drugs / Emtricitabine / Emtricitabine - pharmacology / Exposure / Female / Health aspects / HIV / Human immunodeficiency virus / Infections / Insertion / Macaca / Macaca nemestrina / Medical research / Medicine and Health Sciences / Pharmaceuticals / Physical Sciences / Prophylaxis / Retroviruses, Simian / Simian Acquired Immunodeficiency Syndrome - prevention & control / Simian Acquired Immunodeficiency Syndrome - transmission / Simian immunodeficiency virus / Sustained release / Tenofovir / Tenofovir - pharmacology / Trichomonas vaginalis / Vagina / Viruses