Abstract
The ability to successfully develop a safe and effective vaccine for the prevention of HIV infection has proven challenging. Consequently, alternative approaches to HIV infection prevention have been pursued, and there have been a number of successes with differing levels of efficacy. At present, only two oral preexposure prophylaxis (PrEP) products are available, Truvada and Descovy. Descovy is a newer product not yet indicated in individuals at risk of HIV-1 infection from receptive vaginal sex, because it still needs to be evaluated in this population. A topical dapivirine vaginal ring is currently under regulatory review, and a long-acting (LA) injectable cabotegravir product shows strong promise. Although demonstrably effective, daily oral PrEP presents adherence challenges for many users, particularly adolescent girls and young women, key target populations. This limitation has triggered development efforts in LA HIV prevention options. This article reviews efforts supported by the Bill & Melinda Gates Foundation, as well as similar work by other groups, to identify and develop optimal LA HIV prevention products. Specifically, this article is a summary review of a meeting convened by the foundation in early 2020 that focused on the development of LA products designed for extended delivery of tenofovir alafenamide (TAF) for HIV prevention. The review broadly serves as technical guidance for preclinical development of LA HIV prevention products. The meeting examined the technical feasibility of multiple delivery technologies, in vivo pharmacokinetics, and safety of subcutaneous (SC) delivery of TAF in animal models. Ultimately, the foundation concluded that there are technologies available for long-term delivery of TAF. However, because of potentially limited efficacy and possible toxicity issues with SC delivery, the foundation will not continue investing in the development of LA, SC delivery of TAF products for HIV prevention.
Highlights
More than 4 years ago, the Bill & Melinda Gates Foundation initiated investments designed to develop long-acting (LA) delivery of antiretroviral (ARV) drugs for the prevention of HIV transmission in both men and women
This article is a summary review of a meeting convened by the foundation in early 2020 that focused on the development of LA products designed for extended delivery of tenofovir alafenamide (TAF) for HIV prevention
HIV oral preexposure prophylaxis (PrEP) efficacy was first demonstrated with the use of oral truvada (FTC/tenofovir disoproxil fumarate (TDF)) in men who have sex with men (MSM) and transgender women (TGW),[11] and in sero-discordant couples.[12]
Summary
More than 4 years ago, the Bill & Melinda Gates Foundation (the foundation) initiated investments designed to develop long-acting (LA) delivery of antiretroviral (ARV) drugs for the prevention of HIV transmission in both men and women. These new foundation-supported efforts focusing on TAF were conducted independently and in parallel with development of other LA prevention products, supported in partnerships with the foundation These included, the injectable suspension formulation of the integrase inhibitor, cabotegravir[3] (CAB-LA; GlaxoSmith-Kline; ViiV), that had originally been developed as an LA treatment option to be used in combination with the LA injectable suspension formulation of rilpivirine ( Janssen)[4]; and, the 30-day dapivirine vaginal ring (International Partnership of Microbicides).[5,6]. These products were in advanced development at the time the foundation initiated its investments in the LA ARV portfolio described here. This article summarizes the product preclinical development studies along with the data analyses conducted by the meeting participants that led to this conclusion
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