1. Extended Postexposure Protection Against Vaginal Simian/Human Immunodeficiency Virus Infection With Tenofovir Alafenamide Fumarate/Elvitegravir Inserts in Macaques.
- Author
-
Makarova N, Singletary T, Peet MM, Mitchell J, Bachman S, Holder A, Dinh C, Lipscomb J, Agrahari V, Mendoza M, Pan Y, Heneine W, Clark MR, García-Lerma JG, Doncel GF, and Smith JM
- Subjects
- Animals, Female, Vagina virology, Vagina drug effects, Simian Immunodeficiency Virus drug effects, HIV Infections prevention & control, HIV Infections virology, Administration, Intravaginal, Macaca mulatta, Disease Models, Animal, Tenofovir administration & dosage, Tenofovir analogs & derivatives, Quinolones administration & dosage, Quinolones pharmacology, Alanine administration & dosage, Simian Acquired Immunodeficiency Syndrome prevention & control, Simian Acquired Immunodeficiency Syndrome virology, Anti-HIV Agents administration & dosage, Adenine analogs & derivatives, Adenine administration & dosage, Adenine pharmacology, Adenine therapeutic use
- Abstract
Vaginal inserts that can be used on demand before or after sex may be a desirable human immunodeficiency virus (HIV) prevention option for women. We recently showed that inserts containing tenofovir alafenamide fumarate (TAF, 20 mg) and elvitegravir (EVG, 16 mg) were highly protective against repeated simian/human immunodeficiency virus (SHIV) vaginal exposures when administered to macaques 4 hours before or after virus exposure (93% and 100%, respectively). Here, we show in the same macaque model that insert application 8 hours or 24 hours after exposure maintains high efficacy (94.4% and 77.2%, respectively). These data extend the protective window by TAF/EVG inserts and inform their clinical development for on-demand prophylaxis in women., Competing Interests: Potential conflicts of interest. J. G. G.-L. and W. H. are named in US government patents on “Inhibition of HIV infection through chemoprophylaxis” (US patents 9,044,509 B2; 9,579,333 B2; 9,937,191 B2 and 10,335,423 B2) and “HIV post-exposure prophylaxis” (US patent 11,191,763 B2), and the US government patent application on “HIV preexposure prophylaxis.” (US 2022/0265689 A1). M. M. P., V. A., G. F. D., and M. R. C. are named in patent applications US 2021/0379089 A1 on “Pharmaceutical compositions and methods of making on-demand solid dosage formulations,” inventions that were developed under a USAID-funded cooperative agreement. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2023.)
- Published
- 2024
- Full Text
- View/download PDF