HIV

Long-acting injectable cabotegravir is highly effective for the prevention of HIV infection in cisgender men and transgender women who have sex with men

Date: 
5/18/20

The HIV Prevention Trials Network (HPTN) announced today results from HPTN 083, a global randomized, controlled, double-blind study that compared the safety and efficacy of long-acting injectable cabotegravir (CAB LA) to daily oral tenofovir/emtricitabine (TDF/FTC) (Truvada) for pre-exposure prophylaxis (PrEP). The study showed that CAB LA lowered HIV incidence among cisgender men and transgender women who have sex with men. During a planned review of study data, an independent Data and Safety Monitoring Board (DSMB) recommended that the study results be announced as soon as possible. The study sponsor, the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, agreed with this recommendation.

Health Topics: 
HIV
LA/ER Injectable Therapy

    Integration of Computational and Experimental Approaches to Elucidate Mechanisms of First-Pass Lymphatic Drug Sequestration and Long-Acting Pharmacokinetics of the Injectable Triple-HIV Drug Combination TLC-ART 101

    Date: 
    5/15/20
    Citation: 

    Perazzolo S, Shireman LM, McConnachie LA, Koehn J, Kinman L, Lee W, Lane S, Collier AC, Shen DD, Ho RJY. Integration of Computational and Experimental Approaches to Elucidate Mechanisms of First-Pass Lymphatic Drug Sequestration and Long-Acting Pharmacokinetics of the Injectable Triple-HIV Drug Combination TLC-ART 101. J Pharm Sci. 2020 May;109(5):1789-1801. doi: 10.1016/j.xphs.2020.01.016. Epub 2020 Jan 29. PMID: 32006525.

    TLC-ART101 is a long-acting triple-HIV drug combination of lopinavir-ritonavir-tenofovir in one nanosuspension intended for subcutaneous injection. After a single TLC-ART 101 administration in nonhuman primates, drug concentrations in both plasma and HIV-target lymph node mononuclear cells were sustained for 2 weeks. Nevertheless, the mechanisms leading to the targeted long-acting pharmacokinetics remain elusive. Therefore, an intravenous study of TLC-ART 101 in nonhuman primates was conducted to elucidate the degree of association of drugs in vivo, estimate subcutaneous bioavailability, and refine a mechanism-based pharmacokinetic (MBPK2) model. The MBPK2 model considers TLC-ART 101 systemic drug clearances, nanoparticle-associated/dissociated species, more detailed mechanisms of lymphatic first-pass retention of associated-drugs after subcutaneous administrations, and the prediction of drug concentration time-courses in lymph node mononuclear cells. 

    Health Topics: 
    HIV

      A Conjoint Analysis of the Acceptability of Targeted Long-Acting Injectable Antiretroviral Therapy Among Persons Living with HIV in the U.S

      Date: 
      4/15/20
      Citation: 

      Simoni JM, Tapia K, Lee SJ, Graham SM, Beima-Sofie K, Mohamed ZH, Christodoulou J, Ho R, Collier AC. A Conjoint Analysis of the Acceptability of Targeted Long-Acting Injectable Antiretroviral Therapy Among Persons Living with HIV in the U.S. AIDS Behav. 2020 Apr;24(4):1226-1236. doi: 10.1007/s10461-019-02701-7. PMID: 31655915; PMCID: PMC7085450.

      With long-acting injectable antiretroviral therapy likely to be a treatment option for people living with HIV (PLWH), it is critical to assess its acceptability among potential end-users. Based on formative qualitative work and our own ongoing development of targeted long-acting products in nanosuspension formulations, we created eight hypothetical medication scenarios varying along six dichotomous attributes: administration location (home versus [vs.] clinic), dosing frequency (every 2 weeks vs. 1 week), injections per dose (one vs. two), injection pain (mild vs. moderate), injection site reaction (mild vs. moderate), and effectiveness (better vs. same as pills). PLWH from three outpatient care clinics in Seattle, WA and Riverside, CA rated acceptability (i.e., willingness to try each hypothetical medication) from 0 (very unlikely) to 100 (very likely). In conjoint analyses, we examined level and correlates of acceptability, the impact of each attribute on overall acceptability, and moderators of this effect. 

      Health Topics: 
      HIV
      LA/ER Injectable Therapy

        Long-Acting Cabotegravir and Rilpivirine for Maintenance of HIV-1 Suppression

        Date: 
        3/4/20
        Citation: 

        Swindells, J.-F. Andrade-Villanueva, G.J. Richmond, G. Rizzardini, A. Baumgarten, M. Masiá, G. Latiff, V. Pokrovsky, F. Bredeek, G. Smith, P. Cahn, Y.-S. Kim, S.L. Ford, C.L. Talarico, P. Patel, V. Chounta, H. Crauwels, W. Parys, S. Vanveggel, J. Mrus, J. Huang, C.M. Harrington, K.J. Hudson, D.A. Margolis, K.Y. Smith, P.E. Williams, and W.R. Spreen. Long-Acting Cabotegravir and Rilpivirine for Maintenance of HIV-1 SuppressionS. N Engl J Med 2020;382:1112-23.DOI: 10.1056/NEJMoa1904398

        Simplified regimens for the treatment of human immunodeficiency virus type 1 (HIV-1) infection may increase patient satisfaction and facilitate adherence.

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

          Long-Acting Cabotegravir and Rilpivirine after Oral Induction for HIV-1 Infection

          Date: 
          3/19/20
          Citation: 

          C. Orkin, K. Arasteh, M. Górgolas Hernández‑Mora, V. Pokrovsky, E.T. Overton, P.‑M. Girard, S. Oka, S. Walmsley, C. Bettacchi, C. Brinson, P. Philibert, J. Lombaard, M. St. Clair, H. Crauwels, S.L. Ford, P. Patel, V. Chounta, R. D’Amico, S. Vanveggel, D. Dorey, A. Cutrell, S. Griffith, D.A. Margolis, P.E. Williams, W. Parys, K.Y. Smith, and W.R. Spreen. Long-Acting Cabotegravir and Rilpivirine after Oral Induction for HIV-1 Infection. N Engl J Med 2020;382:1124-35.DOI: 10.1056/NEJMoa1909512

          This study assessed whether switching to monthly injections of long-acting cabotegravir plus rilpivirine would be noninferior to continuing oral therapy in patients with HIV type 1 (HIV-1) who had viral suppression in response to oral induction therapy.

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

            A multi-site study of women living with HIV's perceived barriers to, and interest in, long-acting injectable anti-retroviral therapy.

            Date: 
            3/2/20
            Citation: 

            Philbin MM, Parish C, Kinnard EN, Reed SE, Kerrigan D, Alcaide M, Cohen MH, Sosanya O, Sheth AN, Adimora AA, Cocohoba J, Goparaju L, Golub ET, Fischl M, Metsch LR. A multi-site study of women living with HIV's perceived barriers to, and interest in, long-acting injectable anti-retroviral therapy. J Acquir Immune Defic Syndr. 2020 Mar 2. doi: 10.1097/QAI.0000000000002337. PMID: 32141961

            Adherence to antiretroviral therapy (ART) is imperative for viral suppression and reducing HIV transmission, but many people living with HIV report difficultly sustaining long-term adherence. Long-acting injectable (LAI) ART has the potential to transform HIV treatment and prevention. However, little LAI ART-related behavioral research has occurred among women, particularly outside of clinical trials.

            Health Topics: 
            HIV
            LA/ER Injectable Therapy

              Long-acting rilpivirine (RPV LA) pre-exposure prophylaxis does not inhibit vaginal transmission of RPV-resistant HIV-1 nor select for high frequency drug resistance in humanized mice.

              Date: 
              1/22/20
              Citation: 

              Melody K, Roy CN, Kline C, Cottrell ML, Evans D, Shutt K, Pennings PS, Keele BF, Bility M, Kashuba ADM, Ambrose Z. Long-acting rilpivirine (RPV LA) pre-exposure prophylaxis does not inhibit vaginal transmission of RPV-resistant HIV-1 or select for high frequency drug resistance in humanized mice. J Virol. 2020 Mar 31;94(8):e01912-19. doi: 10.1128/JVI.01912-19. Print 2020 Mar 31. PMID: 31969438; PMCID: PMC7108851.

              As a long-acting formulation of the non-nucleoside reverse transcriptase inhibitor rilpivirine (RPV LA) has been proposed for use as pre-exposure prophylaxis (PrEP) and the prevalence of transmitted RPV-resistant viruses can be relatively high, we evaluated the efficacy of RPV LA to inhibit vaginal transmission of RPV-resistant HIV-1 in humanized mice. 

              Health Topics: 
              HIV
              Pre-exposure Prophylaxis (PrEP)

                Addressing the global burden of hepatitis B virus while developing long-acting injectables for the prevention and treatment of HIV

                Date: 
                12/20/19
                Citation: 

                Bollinger RC, Thio CL, Sulkowski MS, McKenzie-White J, Thomas DL, Flexner C. Addressing the global burden of hepatitis B virus while developing long-acting injectables for the prevention and treatment of HIV. Lancet HIV. 2020;7(6):e443-e448. doi:10.1016/S2352-3018(19)30342-X. PMID: 31870675; PMCID: PMC7376366.

                The first long-acting formulations of HIV drugs are undergoing regulatory review for use in maintenance of viral suppression in people with HIV.

                Health Topics: 
                HIV
                LA/ER Injectable Therapy
                Viral Hepatitis

                  Long-acting implants to treat and prevent HIV infection

                  Date: 
                  12/6/19
                  Citation: 

                  Weld ED, Flexner C. Long-acting implants to treat and prevent HIV infection. Curr Opin HIV AIDS. 2020 Jan;15(1):33-41. doi: 10.1097/COH.0000000000000591. PMID: 31764198; PMCID: PMC7050620.

                  Subcutaneous implants are a promising technology to enable long-acting parenteral delivery of antiretroviral drugs (ARV) because they may be able to provide protective drugs concentrations for a year or longer following a single implant. The present review covers the current status of preclinical and clinical development of antiretroviral implants.

                  Health Topics: 
                  HIV
                  LA/ER Implantable Therapy
                  Viral Hepatitis

                    Pages