Research efforts to develop topical microbicides for intravaginal use for the prevention of sexually transmitted infections (STI) including HIV have been ongoing for over a decade. In the past year an estimated 4.3 million people became newly infected with HIV. Women now represent almost half of all adults living with HIV/AIDS. The need for a female controlled STI preventive product is well understood. Preclinical safety and efficacy testing of topical microbicide products must be performed prior to human use to assess the product's effects on the vaginal ecosystem and to assess potential anti-HIV activity. We have developed a useful model to evaluate the safety of topical microbicide products after vaginal use in the pigtailed macaque. We have used this model to study the effects of single and repeated applications of microbicides on vaginal microflora and epithelium. We have conducted preclinical safety and pharmacokinetic studies of vaginal gel formulations containing UC781 ( 1% and 0.1%) and tenofovir (1%) in this macaque model. In addition, we have the ability to image (MRI) product dispersal and transport in the female reproductive tract. In this proposed cooperative agreement, a novel delivery system for topical microbicides, vaginal films, will be compared to vaginal gel formulations. We will use our macaque model to assess safety, dispersal and pharmacokinetic characteristics of various film formulations containing UC781 and/or tenofovir, and compare these findings to those compiled for gel formulations. Finally, we will assess the efficacy of each of the developed film products using a macaque model for RT-SHIV infection. These studies will in part guide the optimization of a combination topical microbicide delivery system.
An effective topical microbicide product is desperately needed to mitigate the ongoing HIV pandemic. These macaque studies will provide data integral to the optimization of product safety, delivery and efficacy, with an end goal of providing a combination topical microbicide product poised for advancement to clinical trials.
|Guthrie, K M; Rohan, L; Rosen, R K et al. (2018) Vaginal film for prevention of HIV: using visual and tactile evaluations among potential users to inform product design. Pharm Dev Technol 23:311-314|
|Grab, Sheila; Rohan, Lisa C (2018) A Quantitative Disintegration Method for Polymeric Films. J Pharm Innov 13:321-329|
|Robinson, Jennifer A; Marzinke, Mark A; Fuchs, Edward J et al. (2018) Comparison of the Pharmacokinetics and Pharmacodynamics of Single-Dose Tenofovir Vaginal Film and Gel Formulation (FAME 05). J Acquir Immune Defic Syndr 77:175-182|
|Richardson-Harman, Nicola; Parody, Robert; Anton, Peter et al. (2017) Analytical Advances in the Ex Vivo Challenge Efficacy Assay. AIDS Res Hum Retroviruses 33:395-403|
|Robinson, Jennifer A; Marzinke, Mark A; Bakshi, Rahul P et al. (2017) Comparison of Dapivirine Vaginal Gel and Film Formulation Pharmacokinetics and Pharmacodynamics (FAME 02B). AIDS Res Hum Retroviruses 33:339-346|
|Beamer, May A; Austin, Michele N; Avolia, Hilary A et al. (2017) Bacterial species colonizing the vagina of healthy women are not associated with race. Anaerobe 45:40-43|
|Patel, Sravan Kumar; Rohan, Lisa Cencia (2017) On-demand microbicide products: design matters. Drug Deliv Transl Res 7:775-795|
|Petrina, Melinda A B; Cosentino, Lisa A; Rabe, Lorna K et al. (2017) Susceptibility of bacterial vaginosis (BV)-associated bacteria to secnidazole compared to metronidazole, tinidazole and clindamycin. Anaerobe 47:115-119|
|Coleman, Jenell S; Fuchs, Edward; Aung, Wutyi S et al. (2016) Feasibility of radiolabeled small molecule permeability as a quantitative measure of microbicide candidate toxicity. Contraception 93:331-336|
|Fan, Maria D; Kramzer, Lindsay F; Hillier, Sharon L et al. (2016) Preferred Physical Characteristics of Vaginal Film Microbicides for HIV Prevention in Pittsburgh Women. Arch Sex Behav :|
Showing the most recent 10 out of 34 publications