Recent Publications

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

    Novel drug combination nanoparticles exhibit enhanced plasma exposure and dose-responsive effects on eliminating breast cancer lung metastasis

    Date: 
    3/6/20
    Citation: 

    Mu Q, Yu J, Griffin JI, Wu Y, Zhu L, McConnachie LA, Ho RJY. Novel drug combination nanoparticles exhibit enhanced plasma exposure and dose-responsive effects on eliminating breast cancer lung metastasis. PLoS One. 2020 Mar 6;15(3):e0228557. doi: 10.1371/journal.pone.0228557. PMID: 32142553; PMCID: PMC7059902.

    Early diagnosis along with new drugs targeted to cancer receptors and immunocheckpoints have improved breast cancer survival. However, full remission remains elusive for metastatic breast cancer due to dose-limiting toxicities of heavily used, highly potent drug combinations such as gemcitabine and paclitaxel. Therefore, novel strategies that lower the effective dose and improve safety margins could enhance the effect of these drug combinations. To this end, we developed and evaluated a novel drug combination of gemcitabine and paclitaxel (GT). Leveraging a simple and scalable drug-combination nanoparticle platform (DcNP), we successfully prepared an injectable GT combination in DcNP (GT DcNP). 

      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

              Modelling the intradermal delivery of microneedle array patches for long-acting antiretrovirals using PBPK

              Date: 
              12/6/19
              Citation: 

              Rajoli RKR, Flexner C, Chiong J, Owen A, Donnelly RF, Larraneta E, Siccardi M. Modelling the intradermal delivery of microneedle array patches for long-acting antiretrovirals using PBPK. Eur J Pharm Biopharm. 2019 Nov;144:101-109.  doi: 10.1016/j.ejpb.2019.09.011. Epub 2019 Sep 13. PMID: 31525446; PMCID: PMC6917207.

              Existing HIV therapy using oral antiretrovirals (ARVs) can result in pill fatigue and sub-optimal adherence. Microneedle array patches (MAPs) offer non-invasive, blood-free and painless drug delivery, and may improve patient adherence.

              Health Topics: 
              HIV
              LA/ER Transdermal Drug Delivery

                Transgender Women's Concerns and Preferences on Potential Future Long-Acting Biomedical HIV Prevention Strategies: The Case of Injections and Implanted Medication Delivery Devices (IMDDs)

                Date: 
                10/25/19
                Citation: 

                Rael CT, Martinez M, Giguere R, Bockting W, MacCrate C, Mellmen W, Valente P, Greene GJ, Sherman SG, Footer, KHA, D’Aquila RT, Carballo-Dieguez A, Hope TJ. Transgender Women's Concerns and Preferences on Potential Future Long-Acting Biomedical HIV Prevention Strategies: The Case of Injections and Implanted Medication Delivery Devices (IMDDs). AIDS Behav. 2020 May;24(5):1452-1462. doi: 10.1007/s10461-019-02703-5. PMID: 31654172; PMCID: PMC7181384.

                There are several long-acting biomedical HIV prevention products in the development pipeline, including injections and implanted medication delivery devices (IMDDs). It is critical to understand concerns and preferences on the use of these products in populations that shoulder a disproportionate burden of the HIV epidemic, such as transgender women. This will allow researchers and public health professionals to construct interventions tailored to the needs of these women to promote optimal use of these tools. In studies of other biomedical HIV prevention products (e.g., oral PrEP) it is clear that transgender women have unique concerns related to the use of these strategies.

                Health Topics: 
                HIV
                LA/ER Implantable Therapy
                LA/ER Injectable Therapy
                Pre-exposure Prophylaxis (PrEP)

                  Acceptability of a long-acting injectable HIV prevention product among US and African women: findings from a phase 2 clinical Trial (HPTN 076)

                  Date: 
                  10/22/19
                  Citation: 

                  Tolley EE, Li S, Zangeneh SZ, Atujuna M, Musara P, Justman J, Pathak S, Bekker LG, Swaminathan S, Stanton J, Farrior J, Sista N. Acceptability of a long-acting injectable HIV prevention product among US and African women: findings from a phase 2 clinical Trial (HPTN 076). J Int AIDS Soc. 2019 Oct;22(10):e25408. doi: 10.1002/jia2.25408. PMID: 31651098; PMCID: PMC6813716.

                  High HIV incidence and low adherence to daily oral PrEP among women underscore the need for more acceptable and easier to use HIV prevention products. Global demand for injectable contraception suggests that new, long-acting, injectable formulations could meet this need. We examine acceptability of a long-acting injectable PrEP among HIV-uninfected women in Zimbabwe, South Africa and two United States phase 2 trial sites.

                  Health Topics: 
                  HIV
                  LA/ER Injectable Therapy
                  Pre-exposure Prophylaxis (PrEP)

                    Considerations and challenges in developing novel long-acting antiretrovirals modalities for treatment and prevention of HIV-1 infection: a regulatory perspective

                    Date: 
                    9/3/19
                    Citation: 

                    Sampson MR, Troy SB, Belew Y, Arya V, Struble KA. Considerations and challenges in developing novel long-acting antiretrovirals modalities for treatment and prevention of HIV-1 infection: a regulatory perspective. Curr Opin HIV AIDS. 2019 Sep 3. doi: 10.1097/COH.0000000000000587. [Epub ahead of print]. PMID: 31483323.

                    Outline some regulatory considerations and scientific challenges related to the development of long-acting antiretrovirals (ARVs) for the treatment and prevention of HIV-1 infection.

                    Health Topics: 
                    HIV
                    LA/ER Implantable Therapy
                    LA/ER Injectable Therapy
                    LA/ER Oral Therapy
                    LA/ER Transdermal Drug Delivery
                    Pre-exposure Prophylaxis (PrEP)

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