Imperfect adherence to daily oral antiretroviral formulations is a major obstacle to the effectiveness of HIV therapy and pre-exposure prophylaxis (PrEP). An important and novel solution to this problem is long-acting/extended-release injectable antiretrovirals (LA/ER ARV's) that can be administered periodically in a clinic setting, eliminating the problems of pill fatigue, forgetfulness, missed doses, and privacy concerns related to pill taking. This strategy is especially important for vulnerable populations, including children, adolescents, pregnant women, intravenous drug users, and when HIV disclosure is associated with risk of stigma and/or violence. Because the development of these products is so complex and challenging, the Long Acting/Extended Release Antiretroviral Resource Program (LEAP) will assist investigators working on these new approaches by identifying solutions to common problems that take advantage of the best available technological and regulatory strategies. This program will provide a centralized resource to: 1) facilitate innovation by providing investigators with access to experts from the scientific, pharmaceutical, regulatory, and HIV-affected communities, 2) develop a web-based portal that will serve as a communications and data hub for researchers by creating a repository for important laboratory and clinical information and results, and 3) provide a state-of-the-art computer based modeling and simulation service that will guide selection of formulation, dose, and route of administration for new products. Because development of LA/ER ARV's currently entails significant scientific and financial risks, the field is moving slowly and resources such a these are necessary to facilitate development of new and existing compounds. Expected outcomes of this Program include more efficient translation of laboratory-based research into clinical trials and eventual drug approval, new products and formulations in preclinical and clinical stages of development, regulatory dialog and guidance for investigators, and print and web-based publications including systematic reviews of shared data that can serve as the basis for future product development.

Public Health Relevance

Current treatment and prevention of HIV may require taking pills daily for years or decades. This resource program will encourage the development of long-acting injectable anti-HIV drugs that can replace current oral medications, and require injection only a few times a year. We will support investigators in this field with access to scientific, pharmaceutical, regulatory, and community-based experts and services.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Resource-Related Research Projects (R24)
Project #
Application #
Study Section
Special Emphasis Panel (ZAI1)
Program Officer
Livnat, Daniella
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Johns Hopkins University
Internal Medicine/Medicine
Schools of Medicine
United States
Zip Code
Rajoli, R K R; Podany, A T; Moss, D M et al. (2018) Modelling the long-acting administration of anti-tuberculosis agents using PBPK: a proof of concept study. Int J Tuberc Lung Dis 22:937-944
Flexner, Charles (2018) Antiretroviral implants for treatment and prevention of HIV infection. Curr Opin HIV AIDS 13:374-380
Swindells, S; Siccardi, M; Barrett, S E et al. (2018) Long-acting formulations for the treatment of latent tuberculous infection: opportunities and challenges. Int J Tuberc Lung Dis 22:125-132
Rajoli, Rajith K R; Back, David J; Rannard, Steve et al. (2018) In Silico Dose Prediction for Long-Acting Rilpivirine and Cabotegravir Administration to Children and Adolescents. Clin Pharmacokinet 57:255-266
Weld, Ethel D; Rana, Md Sohel; Dallas, Ronald H et al. (2018) Interest of Youth Living with HIV in Long-Acting Antiretrovirals. J Acquir Immune Defic Syndr :
Bakshi, Rahul P; Tatham, Lee M; Savage, Alison C et al. (2018) Long-acting injectable atovaquone nanomedicines for malaria prophylaxis. Nat Commun 9:315
Flexner, Charles W; Clayden, Polly; Venter, Willem D F (2017) Why a universal antiretroviral regimen? Curr Opin HIV AIDS 12:315-317
Jacobson, Jeffrey M; Flexner, Charles W (2017) Universal antiretroviral regimens: thinking beyond one-pill-once-a-day. Curr Opin HIV AIDS 12:343-350
Owen, Andrew; Rannard, Steve (2016) Strengths, weaknesses, opportunities and challenges for long acting injectable therapies: Insights for applications in HIV therapy. Adv Drug Deliv Rev 103:144-56
Nelson, Antoinette G; Zhang, Xiaoping; Ganapathi, Usha et al. (2015) Drug delivery strategies and systems for HIV/AIDS pre-exposure prophylaxis and treatment. J Control Release 219:669-680