Development of Ultra Long-Acting Oral HIV Therapies
NIH/NIAID: 1R01AI131416-01; Andrew Martin Bellinger (PI); 03/22/17 - 02/28/22
NIH/NIAID: 1R01AI131416-01; Andrew Martin Bellinger (PI); 03/22/17 - 02/28/22
NIH/NIAID: 4R01AI073146-09; Victor J. Garcia-Martinez (PI); 01/05/02 - 07/31/17
NIH/NIAID: 5R01AI117740-03; Christopher J. Destache (PI); 02/04/16 - 01/31/18
Non-adherence to anti-retroviral therapy by HIV+ patients results in increased viral loads and risk of emergence of drug-resistant HIV strains. This poses a major public health threat. Lyndra Co. has developed an orally available, long-acting drug delivery system that it will now formulate to deliver anti-retrovirals.
In this application, researchers propose to utilize novel synthetic chemistry to develop a series of aliphatic tenofovir prodrugs designed to greatly enhance cellular uptake and to provide prolonged intracellular exposure to molecules with potent antiviral activity. They will further extend systemic exposure to these compounds by delivering them in slow-release nanoparticle formulations. They believe that with this “dual-modulation” of drug presentation we will provide systemic exposure to therapeutic concentrations of highly active antiviral compounds for periods of at least four weeks following intramuscular injection.
Nelson AG, Zhang X, Ganapathi U, et al. Drug delivery strategies and systems for HIV/AIDS pre-exposure prophylaxis and treatment. J Control Release. 2015;219:669-680. doi:10.1016/j.jconrel.2015.08.042. PMID: 26315816; PMCID: PMC4879940.
The year 2016 will mark an important milestone - the 35th anniversary of the first reported cases of HIV/AIDS. Antiretroviral Therapy (ART) including Highly Active Antiretroviral Therapy (HAART) drug regimens is widely considered to be one of the greatest achievements in therapeutic drug research having transformed HIV infection into a chronically managed disease. Unfortunately, the lack of widespread preventive measures and the inability to eradicate HIV from infected cells highlight the significant challenges remaining today.
Kraft JC, McConnachie LA, Koehn J, et al. Long-acting combination anti-HIV drug suspension enhances and sustains higher drug levels in lymph node cells than in blood cells and plasma. AIDS. 2017;31(6):765-770. doi:10.1097/QAD.0000000000001405. PMID: 28099191; PMCID: PMC5345888.
Objective:
To determine if a combination of anti-HIV drugs-tenofovir (TFV), lopinavir (LPV), and ritonavir (RTV)-in a lipid-stabilized nanosuspension (called TLC-ART101) could enhance and sustain intracellular drug levels and exposures in lymph node and blood cells above those in plasma.
Design:
Four macaques were given a single dose of TLC-ART101 subcutaneously. Drug concentrations in plasma and mononuclear cells of the blood (PBMCs) and lymph nodes (LNMCs) were analyzed using a validated combination LC-MS/MS assay.
Ho RJ, Yu J, Li B, et al. Systems Approach to targeted and long-acting HIV/AIDS therapy. Drug Deliv Transl Res. 2015;5(6):531-539. doi:10.1007/s13346-015-0254-y. PMID: 26315144; PMCID: PMC4826474.
NIH/NIAID 5R01AI120748-02; Marc M. Baum (PI); 06/26/15 - 05/31/20
The purpose of this Funding Opportunity Announcement (FOA) is to solicit applications from single institutions, or consortia of institutions, to identify existing anti-HIV molecules...