TY - JOUR
T1 - Tenofovir Alafenamide for HIV Prevention
T2 - Review of the Proceedings from the Gates Foundation Long-Acting TAF Product Development Meeting
AU - Romano, Joseph W.
AU - Baum, Marc M.
AU - Demkovich, Zach R.
AU - DIana, Frank
AU - Dobard, Charles
AU - Feldman, Paul L.
AU - Garcia-Lerma, J. Gerardo
AU - Grattoni, Alessandro
AU - Gunawardana, Manjula
AU - Ho, Duy Khiet
AU - Hope, Thomas J.
AU - Massud, Ivana
AU - Milad, Mark
AU - Moss, John A.
AU - Pons-Faudoa, Fernanda P.
AU - Roller, Shane
AU - Van Der Straten, Ariane
AU - Srinivasan, Selvi
AU - Veazey, Ronald S.
AU - Zane, Doris
N1 - Funding Information:
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’s 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).
Funding Information:
NW (SLAP-HIV grant; funded by NIH/DAIDS): nondegradable reservoir implant
Publisher Copyright:
© Joseph W. Romano et al. 2021; Published by Mary Ann Liebert, Inc. 2021.
PY - 2021/6
Y1 - 2021/6
N2 - 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.
AB - 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.
KW - HIV PrEP
KW - TAF
KW - long-acting
UR - http://www.scopus.com/inward/record.url?scp=85107576998&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85107576998&partnerID=8YFLogxK
U2 - 10.1089/aid.2021.0028
DO - 10.1089/aid.2021.0028
M3 - Review article
C2 - 33913760
AN - SCOPUS:85107576998
SN - 0889-2229
VL - 37
SP - 409
EP - 420
JO - AIDS Research and Human Retroviruses
JF - AIDS Research and Human Retroviruses
IS - 6
ER -