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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 409-420 |
| Number of pages | 12 |
| Journal | AIDS research and human retroviruses |
| Volume | 37 |
| Issue number | 6 |
| DOIs | |
| State | Published - Jun 2021 |
Funding
RTI International work was supported by the Bill & Me-linda Gates Foundation, Grant No. OPP1149227, with funding for the NHP study provided by the United States Agency for International Development (USAID) through the U.S. President\u2019s Emergency Plan for AIDS Relief (PEPFAR) (AID-OAA-A-14-00012). Houston Methodist Research Institute work was supported by funding from the National Institutes of Health, National Institute of Allergy and Infectious Diseases (R01AI120749; A.G.), the National Institutes of Health, National Institute of General Medical Sciences (R01GM127558; A.G.) and Gilead Sciences (A.G.). F.P.P. received funding support from Tecnologico de Monterrey and Consejo Nacional de Ciencia y Tecnologia. Oak Crest Institute of Science work was supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under award no. R01AI120748. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The NW group received funding from the National Institute of Allergy and Infectious Disease of the National Institutes of Health (UM1 AI120184). NW (SLAP-HIV grant; funded by NIH/DAIDS): nondegradable reservoir implant
Keywords
- HIV PrEP
- TAF
- long-acting
ASJC Scopus subject areas
- Immunology
- Virology
- Infectious Diseases
