Tuberculosis

A long-acting formulation of rifabutin is effective for prevention and treatment of Mycobacterium tuberculosis

Date: 
8/8/22
Citation: 

Kim M, Johnson CE, Schmalstig AA, Annis A, Wessel SE, Van Horn B, Schauer A, Exner AA, Stout JE, Wahl A, Braunstein M, Victor Garcia J, Kovarova M. A long-acting formulation of rifabutin is effective for prevention and treatment of Mycobacterium tuberculosis. Nat Commun. 2022 Aug 8;13(1):4455. doi: 10.1038/s41467-022-32043-3. PMID: 35941109.

Tuberculosis (TB) is a communicable disease caused by Mycobacterium tuberculosis (Mtb) and is a major cause of morbidity and mortality. Successful treatment requires strict adherence to drug regimens for prolonged periods of time. Long-acting (LA) delivery systems have the potential to improve adherence.

Health Topics: 
Tuberculosis

    Notice of Special Interest (NOSI): Sustained Release of Antivirals for Treatment or Prevention of HIV or Treatment of Latent TB/HBV (SRATP)

    Grant Source: 
    NIH/NIAID

    Clinical experience for HIV treatment and prevention has demonstrated that adherence to a drug regimen schedule is a significant factor in the success of the HIV treatment regime and/or prevention strategies. Effective treatment of HIV-infected individuals requires strict adherence to a multi-component regimen of antiretroviral agents taken at least daily for the remainder of a patient’s life. Non-adherence can lead to emergence of drug-resistance and loss of therapeutic effectiveness. Among people living with HIV, morbidity and mortality is increasingly driven by co-infections, such as tuberculosis (TB) and hepatitis B, where the compliance and completion of prolonged multidrug regimens are significant factors in treatment success.

    Effective prevention requires that the inhibitor be present at the right time, place, and concentration to stop HIV transmission and acquisition. Although many factors (social, behavioral, and individual preference) can influence adherence, the use of drug delivery systems to provide for a longer therapeutic exposure or window of protection and/or less frequent administration may improve their consistent use, reduce dosing intervals, and potentially improve adherence to the drug regimens.

    Development of safe, effective, and well-tolerated sustained release (SR)/long acting (LA) products and strategies that maintain consistent and effective drug levels in plasma and target tissues for longer periods of time is critical for successful treatment and prevention of HIV and HIV-associated co-infections.

    Health Topics: 
    HIV
    Tuberculosis

      Landmark trial demonstrates effectiveness of shortened TB treatment

      Date: 
      11/2/20

      The ACTG is pleased to share the primary results of Study 31/A5349, which were presented at the 51st virtual Union World Conference on Lung Health on October 21st, 2020. This important study showed that the four-month regimen of rifapentine, isoniazid, pyrazinamide, and moxifloxacin (RPT-MOX) was non-inferior to the currently recommended six-month regimen of rifampicin, isoniazid, ethambutol, and pyrazinamide for the treatment of drug-susceptible pulmonary TB. RPT-MOX was also safe and well-tolerated by patients. A second four-month regimen of rifapentine, isoniazid, pyrazinamide, and ethambutol failed to meet the non-inferiority margin. 

      Health Topics: 
      Tuberculosis

        A year-long extended release nanoformulated cabotegravir prodrug

        Date: 
        8/15/20
        Citation: 

        Kulkarni TA, Bade AN, Sillman B, et al. A year-long extended release nanoformulated cabotegravir prodrug. Nat Mater. 2020;19(8):910-920. doi:10.1038/s41563-020-0674-z

        Long-acting cabotegravir (CAB) extends antiretroviral drug administration from daily to monthly. However, dosing volumes, injection site reactions and health-care oversight are obstacles towards a broad usage. The creation of poloxamer-coated hydrophobic and lipophilic CAB prodrugs with controlled hydrolysis and tissue penetrance can overcome these obstacles. To such ends, fatty acid ester CAB nanocrystal prodrugs with 14, 18 and 22 added carbon chains were encased in biocompatible surfactants named NMCAB, NM2CAB and NM3CAB and tested for drug release, activation, cytotoxicity, antiretroviral activities, pharmacokinetics and biodistribution.

        Health Topics: 
        HIV
        LA/ER Injectable Therapy
        Tuberculosis

          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

            Emerging Technologies for New Solutions in Global Health Priority Areas (Round 23)

            Grant Source: 
            Gates

            ​THE OPPORTUNITY
            A set of rapidly-evolving technologies is changing the world and expanding the realm of the possible. These emerging technologies include – but are not limited to – artificial intelligence, materials science, wearable sensors, synthetic biology, nanotechnology, microscopy, augmented and virtual reality, geospatial mapping, robotics, and DNA sequencing. 
            DEADLINE: 10 APR 2019 - 11:30AM PDT

            Health Topics: 
            Tuberculosis

              Accelerating impact of long-acting technologies in low- and middle-income countries (LMICs)

              Grant Source: 
              UNITAID

              Safe and efficacious medicines are available for the prevention and treatment of major diseases, but their effectiveness can be compromised by poor treatment completion. Lack of adherence can worsen clinical outcomes, leading to increased mortality, persistent transmission and increased drug resistance in the case of antimicrobials and antivirals. Analyses of treatment and prevention of HIV, malaria, and TB within public health programs show wide disparities in rates of completion, especially among specific populations and regions.

              Application Deadline: 23 April 2019

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

                Predicting drug-drug interactions between rifampicin and long-acting cabotegravir and rilpivirine using PBPK modelling

                Date: 
                12/19/18
                Citation: 

                Rajoli RKR, Curley P, Chiong J, et al. Predicting drug-drug interactions between rifampicin and long-acting cabotegravir and rilpivirine using PBPK modelling. J Infect Dis. 2019 May 5;219(11):1735-1742. doi: 10.1093/infdis/jiy726. PMID: 30566691; PMCID: PMC6500558.

                Cabotegravir and rilpivirine are two long-acting (LA) ARVs that can be administered intramuscularly (IM); their interaction with rifampicin, a first-line anti-TB agent, has not been investigated. The aim of this study was to simulate and predict DDIs between these LA ARV agents and rifampicin using PBPK modelling.

                Health Topics: 
                HIV
                LA/ER Injectable Therapy
                Tuberculosis

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