A Phase I Randomized, Placebo-Controlled, Double-Blind Study to Assess Safety, Pharmacokinetics, and Modeled Pharmacodynamics of a Vaginal Insert Containing Tenofovir Alafenamide and Elvitegravir - Trial PACTR202310819162115

Timeline & Enrollment

Summary

Background: Adolescent girls and young women (AGYW) bear the burden of the HIV-1 epidemic, with more than 59% of new infections occurring in women in sub-Saharan Africa (SSA). The daily dosing requirement and systemic side effects, primarily gastrointestinal (GI), have made it difficult, particularly for AGYW, to adhere to daily tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC) for HIV-1 prevention. In SSA, adolescents and young people desire and even prefer on-demand HIV prevention options. Across multiple end-user studies a subset of women consistently indicate a preference for on-demand HIV and multipurpose prevention technologies (MPT) over daily use and even longer-acting products. Recent acceptability data from the contraceptive field, among AGYW in both high- and low-income countries, indicate that many prefer an on-demand, female controlled, peri-coital contraceptive, rather than a daily regimen or even a long-acting product. While there are several US Food and Drug Administration (FDA) approved antivirals to reduce HSV-2 shedding from an infected individual’s genital tract and reduce the duration of painful HSV-2 flare ups, there is no approved HSV-2 primary prevention product. HSV-2 is the most common cause of genital ulcers and is the most prevalent viral sexually transmitted infection (STI) in the US and world-wide, with an estimated 417 million people worldwide living with HSV-2. SSA is the most severely affected region of the world with up to 80% of sexually active women infected with HSV-2 by age 35 years. There are substantial data that HSV-2 and HIV1 infections are synergistic, with asymptomatic shedding of HSV-2 causing increased susceptibility to HIV-1 and increased shedding of HSV-2 among HIV-1 infected individuals. The development of an HIV-1 and HSV-2 primary prevention MPT would have a significant public health impact, especially for AGYW. The objectives of this study will be to examine the safety, Pharmacokinetics, modelled Pharmacodynamics, and acceptability of inserts containing the combination of Tenofovir Alafenamide (TAF) and Elvitegravir (EVG) applied vaginally in HIV-1 negative low-risk women aged 18 – 50 years.

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