Viral Hepatitis

Resources Access for Preclinical Integrated Drug Development (RAPIDD) Program (X01 Clinical Trial Not Allowed)

Grant Source: 
NIH/NIAID

The purpose of this FOA is to provide investigators working on the development of novel therapeutic products for HIV and HIV-associated co-infections (hepatitis B virus, hepatitis C virus, and Mycobacterium tuberculosis) with a mechanism to request NIAID DAIDS preclinical services to fill gaps in their product development efforts and facilitate the advancement of promising therapeutics from bench to clinics.

Health Topics: 
HIV
Viral Hepatitis

    Identification of a novel long-acting 4’-modified nucleoside reverse transcriptase inhibitor against HBV

    Date: 
    3/19/21
    Citation: 

    Higashi-Kuwata N, Hayashi S, Kumamoto H, Ogata-Aoki H, Das D, Venzon D, Hattori SI, Bulut H, Hashimoto M, Otagiri M, Takamune N, Kishimoto N, Davis D, Misumi S, Kakuni M, Tanaka Y, Mitsuya H. Identification of a novel long-acting 4'-modified nucleoside reverse transcriptase inhibitor against HBV. J Hepatol. 2020 Dec 14:S0168-8278(20)33843-5. doi: 10.1016/j.jhep.2020.12.006. Epub ahead of print. PMID: 33333207.

    Although there are currently effective treatment options for HBV, treatment-resistant variants and the need for lifelong therapy pose a significant challenge. Therefore, the development of new treatment options is crucial to improve out-comes and quality of life. Herein, this study reports preclinical evidence showing that the anti-HBV agent, E-CFCP, has potent activity against wild-type and treatment-resistant variants. In addition, once-weekly oral dosing may be possible,which is preferable to the current daily dosing regimens.

    Health Topics: 
    LA/ER Oral Therapy
    Viral Hepatitis

      Development of a long-acting direct-acting antiviral system for hepatitis C virus treatment in swine

      Date: 
      6/2/20
      Citation: 

      Verma M, Chu JN, Salama JAF, et al. Development of a long-acting direct-acting antiviral system for hepatitis C virus treatment in swine. Proc Natl Acad Sci U S A. 2020;117(22):11987-11994. doi:10.1073/pnas.2004746117

      Chronic hepatitis C virus (HCV) infection is a leading cause of cirrhosis worldwide and kills more Americans than 59 other infections, including HIV and tuberculosis, combined. While direct-acting antiviral (DAA) treatments are effective, limited uptake of therapy, particularly in high-risk groups, remains a substantial barrier to eliminating HCV. We developed a long-acting DAA system (LA-DAAS) capable of prolonged dosing and explored its cost-effectiveness. We designed a retrievable coil-shaped LA-DAAS compatible with nasogastric tube administration and the capacity to encapsulate and release gram levels of drugs while resident in the stomach. We formulated DAAs in drug-polymer pills and studied the release kinetics for 1 mo in vitro and in vivo in a swine model. The LA-DAAS was equipped with ethanol and temperature sensors linked via Bluetooth to a phone application to provide patient engagement. 

      Health Topics: 
      HIV
      Tuberculosis
      Viral Hepatitis

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

        Date: 
        6/1/20
        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 Jun;7(6):e443-e448. doi: 10.1016/S2352-3018(19)30342-X. Epub 2019 Dec 20. 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. Although these novel drug formulations could contribute greatly to HIV treatment and prevention efforts, their lack of activity against hepatitis B virus (HBV) could limit their global impact, particularly in populations with high burdens of both HIV and HBV.

        Health Topics: 
        HIV
        LA/ER Injectable Therapy
        Viral Hepatitis

          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