HIV

Development of Ultra Long-Acting Oral HIV Therapies

Grant Source: 
NIH/NIAID

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.

Health Topics: 
HIV
LA/ER Oral Therapy

    Development of Sustained-Release Anti-HIV Nucleoside Phosphonate Nanoparticles

    Grant Source: 
    NIH

    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.

    Health Topics: 
    HIV
    LA/ER Oral Therapy

      Drug delivery strategies and systems for HIV/AIDS pre-exposure prophylaxis and treatment

      Date: 
      12/10/15
      Citation: 

      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.

      Health Topics: 
      HIV

        Long-acting combination anti-HIV drug suspension enhances and sustains higher drug levels in lymph node cells than in blood cells and plasma

        Date: 
        3/27/17
        Citation: 

        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.

        Health Topics: 
        HIV

          Systems Approach to Targeted and Long-acting HIV/AIDS Therapy

          Date: 
          12/5/15
          Citation: 

          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.

          ABSTRACT
          Medication adherence and insufficient drug levels are central to HIV/AIDS disease progression. Recently, Fletcher et al. confirmed that HIV patients on oral antiretroviral therapy had lower intracellular drug concentrations in lymph nodes than in blood. For instance, in the same patient, multiple lymph node drug concentrations were as much as 99 % lower than in blood. This study built upon our previous finding that HIV patients taking oral indinavir had 3-fold lower mononuclear cell drug concentrations in lymph nodes than in blood. As a result, an association between insufficient lymph node drug concentrations in cells and persistent viral replication has now been validated. Lymph node cells, particularly CD4 T lymphocytes, host HIV infection and persistence; CD4 T cell depletion in blood correlates with AIDS progression. With established drug targets to overcome drug insufficiency in lymphoid cells and tissues, we have developed and employed a "Systems Approach" to engineer multi-drug-incorporated particles for HIV treatment.
           
          Health Topics: 
          HIV

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