STI/HIV Prevention

The major research focus of the Rohan Lab is the development of microbicides. Microbicides are products in development that are to be applied vaginally and/or rectally to prevent acquisition of sexually transmitted infections (STIs) like human immunodeficiency virus (HIV). HIV continues to be a global health concern. Both men and women at risk urgently need prevention methods that are within his/her personal control – microbicides fit into this niche of need. Our funded research projects in the area of microbicide product development are listed below.

U19 AI120249 (Program Co-PI with Hillier, S; Project 1 PI; Project 4 PI) NIH/NIAID “Film Antirotroviral Microbicide Evaluation (FAME)”. This integrated preclinical/clinical program (IPCP) will develop a new formulation of the antiretroviral drug MK-2048 that women will use just once a week to prevent HIV infection transmitted through unprotected vaginal intercourse. This research program includes laboratory assessments, animal and in silico modeling, and clinical trials to achieve these goals over 5 years.

UM1 A1106707 (Central Laboratory: Co-Director, Comparative Assessment Core; Program PI: Dezzutti, C) NIH “Laboratory Center (LC): Microbicide Trials Network.” Within the MTN LC, the Rohan Lab is responsible for product formulation-related issues with respect to clinical protocol implementation.

U19 AI113182 (Core B PI; Program PI: Palmer, K) NIH/NIAID “Griffithsin-based Rectal Microbicides for PREvention of Viral ENTry (PREVENT).” The goal of the PREVENT integrated preclinical/clinical program (IPCP) is to develop a Griffithsin-based rectal gel that can be used prior to receptive anal intercourse (RAI) to reduce the risk of HIV infection.

U19 AI113127 (Core C PI; Program PI: Hendrix, C) NIH/NIAID “Delivery of Rectal Enema as Microbicide (DREAM)”.  The goal of the DREAM Program is to develop a single dose pericoital enema to rectally deliver tenofovir (TFV) or its prodrugs and that is capable of providing one week of anti-HIV protection.

  • Clinical trial currently being conducted within this research program
    • DREAM-01: Optimization of a Tenofovir Enema for HIV Prevention (NCT02750540)

U19 AI082639 (Program Co-PI with Hillier, S; Project 1 PI; Core C PI) NIH/NIAID “Alternative formulations of tenofovir and UC781”. This project developed the first vaginal film formulations of microbicides to be advanced from the bench to first in human clinical studies. Specifically film formulations were developed for the nonnucleoside reverse transcriptase inhibitor (NNRTI), dapivirine, and the nucleotide reverse transcriptase inhibitor (NtRTI), tenofovir, and their combination.

  • Clinical trials conducted within this research program
    • A Phase I Trial to Assess the Safety of Dapivirine Gel and Film Formulations : FAME 02 (NCT01548560)
    • Comparison of the Pharmacokinetics and Pharmacodynamics of Single Dose Dapivirine Vaginal Gel and Film Formulation (NCT01924091)
      • Robinson JA, Markzinke MA, Bakshi RP, Fuchs EJ, Radebaugh C, Aung WS, Spiegel H, Coleman JS, Rohan LC, Hendrix CW. Comparison of dapivirine vaginal gel and film formulation pharmacokinetics and pharmacodynamics (FAME 02B). AIDS Res Hum Retroviruses. 2016 Nov 3. [Epub ahead of print]
    • A Phase I Trial to Assess the Safety of Tenofovir Gel and Film Formulations: FAME 04 (NCT01989663)
    • Comparison of the Pharmacokinetics and Pharmacodynamics of Single Dose Tenofovir Vaginal Gel and Film Formulation (NCT02280109)

U19 AI082637 (Core C PI; Program PI: McGowan, I) NIH/NIAID “Combination HIV Antiretroviral Rectal Microbicide Program”. The goal of this project was to develop rectal specific microbicide gel products containing single or combinations of antiretroviral drug candidates.

R33 AI094508 (Co-Investigator; PI: Bronshtein, V) NIH/NIAID “Thermostable Vaginal Probiotic Microbicide”. This project involves the development of appropriate platforms for delivery of probiotics as microbicides. The project includes development of novel polymeric platforms which can be manufactured at low temperature to preserve bacteria viability.

HHSN272201000001C (PI) NIH/Advanced Biosciences Laboratories, Inc. “Release Assays from EVA Ring Segments”. This project studied the in vitro release profile for EVA vaginal rings being developed as devices for the sustained release of microbicide agents to predict clinical exposure and safety. The project also developed novel methods for delivery of hydrophobic drug candidates using strategies such as gel and suppository dosage forms.

R01 AI116292 (Co-Investigator; PI: Hladik, F) NIH/NIAID “Systems and Carcinogenic Impact Assessment of Topical Microbicides on Human Mucosa”. NRTIs like tenofovir and NNRTIs like dapivirine are being evaluated for vaginal or rectal application to prevent sexual HIV transmission. However, NRTIs have side effects that could undermine their effectiveness and cause serious safety concerns with long-term topical use. In this proposal, these side effects will be investigated, with a focus on tenofovir’s possibly carcinogenic effects at the currently-tested concentrations, and determine whether NNRTIs could be a safer alternative.