Recent Publications - HIV

Translation of combination nanodrugs into nanomedicines: lessons learned and future outlook

Date: 
1/10/18
Citation: 

Mu Q, Yu J, McConnachie LA Kraft JC, Gao Y, Gulati GK, Ho RJY. Translation of combination nanodrugs into nanomedicines: lessons learned and future outlook. J Drug Target. Jun-Jul 2018;26(5-6):435-447. doi: 10.1080/1061186X.2017.1419363. Epub 2018 Jan 10. PMID: 29285948; PMCID: PMC6205718.

For the past two decades, the number of research publications on single-agent nanoformulations has grown exponentially. However, formulations advancing to pre-clinical and clinical evaluations that lead to therapeutic products has been limited.

Health Topics: 
HIV

    Development of an oral once-weekly drug delivery system for HIV antiretroviral therapy

    Date: 
    1/9/18
    Citation: 

    Kirtane AR, Abouzid O, Minahan D, et al. Development of an oral once-weekly drug delivery system for HIV antiretroviral therapy. Nat Commun. 2018;9(1):2. Published 2018 Jan 9. doi:10.1038/s41467-017-02294-6. PMID: 29317618; PMCID: PMC5760734.

    The efficacy of antiretroviral therapy is significantly compromised by medication non-adherence. Long-acting enteral systems that can ease the burden of daily adherence have not yet been developed.

    Health Topics: 
    HIV
    LA/ER Oral Therapy

      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

        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

          Long-acting intramuscular cabotegravir and rilpivirine in adults with HIV-1 infection (LATTE-2): 96-week results of a randomised, open-label, phase 2b, non-inferiority trial

          Date: 
          9/23/17
          Citation: 

          Margolis DA, Gonzalez-Garcia J, Stellbrink HJ, et al. Long-acting intramuscular cabotegravir and rilpivirine in adults with HIV-1 infection (LATTE-2): 96-week results of a randomised, open-label, phase 2b, non-inferiority trial. Lancet. 2017;390(10101):1499-1510. doi:10.1016/S0140-6736(17)31917-7. PMID: 28750935.

          The two-drug combination of all-injectable, long-acting cabotegravir plus rilpivirine every 4 weeks or every 8 weeks was as effective as daily three-drug oral therapy at maintaining HIV-1 viral suppression through 96 weeks and was well accepted and tolerated.

          Health Topics: 
          HIV
          LA/ER Injectable Therapy

            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

              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

                Strengths, Weaknesses, Opportunities and Challenges for Long Acting Injectable Therapies: Insights for applications in HIV therapy

                Date: 
                8/1/16
                Citation: 

                Owen A, Rannard S. Strengths, weaknesses, opportunities and challenges for long acting injectable therapies: Insights for applications in HIV therapy. Adv Drug Deliv Rev. 2016;103:144-156. doi:10.1016/j.addr.2016.02.003. PMID: 26916628; PMCID: PMC4935562.

                Many terms have been utilised to describe the LA approach and standardisation would be beneficial.  Ultimately, definitions will depend upon specific indications and routes of delivery.  This review focuses upon the critical importance of potency in achieving the LA outcome for injectable formulations and explores established and emerging technologies that have been employed across indications.

                Health Topics: 
                HIV
                LA/ER Injectable Therapy

                  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)

                    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)

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