HIV

From in silico hit to long-acting late-stage preclinical candidate to combat HIV-1 infection

Date: 
12/26/17
Citation: 

Kudalkar SN, Beloor J, Quijano E, et al. From in silico hit to long-acting late-stage preclinical candidate to combat HIV-1 infection [published correction appears in Proc Natl Acad Sci U S A. 2018 Mar 12;:]. Proc Natl Acad Sci U S A. 2018;115(4):E802-E811. doi:10.1073/pnas.1717932115. PMID: 29279368; PMCID: PMC5789948.

Nonnucleoside reverse transcriptase inhibitors (NNRTIs) that target the viral polymerase have been a key component of the current HIV-1 combination drug regimens; however, these issues hamper them. Thus, the development of novel more effective NNRTIs as anti-HIV-1 agents with fewer long-term liabilities, efficacy on new drug-resistant HIV-1 strains, and less frequent dosing is crucial.

Health Topics: 
HIV

    Multimodal imaging approach to examine biodistribution kinetics of Cabotegravir (GSK1265744) long acting parenteral formulation in rat

    Date: 
    12/28/17
    Citation: 

    Jucker BM, Alsaid H, Rambo M, et al. Multimodal imaging approach to examine biodistribution kinetics of Cabotegravir (GSK1265744) long acting parenteral formulation in rat. J Control Release. 2017;268:102-112. doi:10.1016/j.jconrel.2017.10.017. PMID: 29042321.

    Long-Acting Parenterals (LAPs) have been used in the clinic to provide sustained therapeutic drug levels at a target site, and thereby reducing the frequency of dosing required. In an effort to understand the factors associated with long-acting cabotegravir (GSK1265744 LAP) pharmacokinetic variability, the current study was designed to investigate the temporal relationship between intramuscular (IM) or subcutaneous (SC) drug depot morphology and distribution kinetics with plasma pharmacokinetics.

    Health Topics: 
    HIV
    LA/ER Implantable Therapy
    LA/ER Injectable Therapy

      Creation of a nanoformulated cabotegravir prodrug with improved antiretroviral profiles

      Date: 
      1/15/18
      Citation: 

      Zhou T, Su H, Dash P, et al. Creation of a nanoformulated cabotegravir prodrug with improved antiretroviral profiles. Biomaterials. 2018;151:53-65. doi:10.1016/j.biomaterials.2017.10.023. PMID: 29059541; PMCID: PMC5926202.

      Long-acting parenteral (LAP) antiretroviral drugs have generated considerable interest for treatment and prevention of HIV-1 infection. One new LAP is cabotegravir (CAB), a highly potent integrase inhibitor, with a half-life of up to 54 days, allowing for every other month parenteral administrations. Despite this excellent profile, high volume dosing, injection site reactions and low body fluid drug concentrations affect broad use for virus infected and susceptible people.

      Health Topics: 
      HIV
      LA/ER Injectable Therapy

        Potential Clinical and Economic Value of Long-Acting Preexposure Prophylaxis for South African Women at High-Risk for HIV Infection

        Date: 
        5/15/16
        Citation: 

        Walensky RP, Jacobsen MM, Bekker LG, et al. Potential Clinical and Economic Value of Long-Acting Preexposure Prophylaxis for South African Women at High-Risk for HIV Infection. J Infect Dis. 2016;213(10):1523-1531. doi:10.1093/infdis/jiv523. PMID: 26681778; PMCID: PMC4837902.

        For young South African women at risk for human immunodeficiency virus (HIV) infection, preexposure prophylaxis (PrEP) is one of the few effective prevention options available. Long-acting injectable PrEP, which is in development, may be associated with greater adherence, compared with that for existing standard oral PrEP formulations, but its likely clinical benefits and additional costs are unknown.

        Health Topics: 
        HIV
        Pre-exposure Prophylaxis (PrEP)

          Long-Acting Injectable Preexposure Prophylaxis for HIV Prevention in South Africa: Is There a Will and a Way?

          Date: 
          5/15/16
          Citation: 

          Landovitz RJ, Grinsztejn B. Long-Acting Injectable Preexposure Prophylaxis for HIV Prevention in South Africa: Is There a Will and a Way?. J Infect Dis. 2016;213(10):1519-1520. doi:10.1093/infdis/jiv524. PMID: 26681779.

          Human immunodeficiency virus (HIV) antiretroviral therapy (ART) use results in substantial improvements in HIV-related morbidity and mortality [1, 2] and leads to dramatic reductions in sexual transmission of HIV among heterosexual serodiscordant couples when ART suppresses HIV viremia in the infected partner [3]. 

          Health Topics: 
          HIV
          Pre-exposure Prophylaxis (PrEP)

            Nanodrug formulations to enhance HIV drug exposure in lymphoid tissues and cells: clinical significance and potential impact on treatment and eradication of HIV/AIDS

            Date: 
            2/9/16
            Citation: 

            Shao J, Kraft JC, Li B, et al. Nanodrug formulations to enhance HIV drug exposure in lymphoid tissues and cells: clinical significance and potential impact on treatment and eradication of HIV/AIDS. Nanomedicine (Lond). 2016;11(5):545-564. doi:10.2217/nnm.16.1. PMID: 26892323; PMCID: PMC4910949.

            Although oral combination antiretroviral therapy effectively clears plasma HIV, patients on oral drugs exhibit much lower drug concentrations in lymph nodes than blood. This drug insufficiency is linked to residual HIV in cells of lymph nodes. While nanoformulations improve drug solubility, safety and delivery, most HIV nanoformulations are intended to extend plasma levels.

            Health Topics: 
            HIV

              New perspectives on nanotechnology and antiretroviral drugs: a ‘small’ solution for a big promise in HIV treatment?

              Date: 
              3/27/16
              Citation: 

              Corsi F, Fiandra L, Rizzardini G. New perspectives on nanotechnology and antiretroviral drugs: a 'small' solution for a big promise in HIV treatment?. AIDS. 2016;30(6):963-964. doi:10.1097/QAD.0000000000001026. PMID: 26807964.

              In this issue, Li et al.[1] present a well designed multidisciplinary study, aimed to demonstrate the potential benefit of a multifunctional polymeric nanodevice for delivering HIV treatment.

              Health Topics: 
              HIV
              LA/ER Implantable Therapy

                Co-delivery of HIV-1 entry inhibitor and NNRTI shuttled by nanoparticles: cocktail therapeutic strategy for antiviral therapy

                Date: 
                3/27/16
                Citation: 

                Li W, Yu F, Wang Q, et al. Co-delivery of HIV-1 entry inhibitor and nonnucleoside reverse transcriptase inhibitor shuttled by nanoparticles: cocktail therapeutic strategy for antiviral therapy. AIDS. 2016;30(6):827-838. doi:10.1097/QAD.0000000000000971. PMID: 26595538.

                OBJECTIVES: 
                Traditionally, the antiviral efficacy of classic cocktail therapy is significantly limited by the distinct pharmacokinetic profiles of partner therapeutics that lead to inconsistent in-vivo biodistribution.

                Health Topics: 
                HIV

                  The mixed lineage kinase-3 inhibitor URMC-099 improves therapeutic outcomes for long-acting antiretroviral therapy

                  Date: 
                  1/15/16
                  Citation: 

                  Zhang G, Guo D, Dash PK, et al. The mixed lineage kinase-3 inhibitor URMC-099 improves therapeutic outcomes for long-acting antiretroviral therapy. Nanomedicine. 2016;12(1):109-122. doi:10.1016/j.nano.2015.09.009. PMID: 26472049; PMCID: PMC4728028.

                  During studies to extend the half-life of crystalline nanoformulated antiretroviral therapy (nanoART) the mixed lineage kinase-3 inhibitor URMC-099, developed as an adjunctive neuroprotective agent was shown to facilitate antiviral responses.

                  Health Topics: 
                  HIV

                    In Silico Dose Prediction for Long-Acting Rilpivirine and Cabotegravir Administration to Children and Adolescents

                    Date: 
                    5/24/17
                    Citation: 

                    Rajoli RKR, Back DJ, Rannard S, et al. In Silico Dose Prediction for Long-Acting Rilpivirine and Cabotegravir Administration to Children and Adolescents. Clin Pharmacokinet. 2018;57(2):255-266. doi:10.1007/s40262-017-0557-x. PMID: 28540638; PMCID: PMC5701864.

                    Long-acting injectable antiretrovirals represent a pharmacological alternative to oral formulations and an innovative clinical option to address adherence and reduce drug costs. Clinical studies in children and adolescents are characterised by ethical and logistic barriers complicating the identification of dose optimisation.

                    Health Topics: 
                    HIV
                    LA/ER Injectable Therapy
                    Pediatric Formulations

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