Rifampin-Based Tuberculosis Treatment Versus Rifabutin-Based Tuberculosis Treatment in Persons With HIV
Condition: HIV Infection; Tuberculosis
MeSH terms: Tuberculosis
Intervention: Standard-dose Lopinavir/Ritonavir; Double-dose Lopinavir/Ritonavir; Raltegravir; Isoniazid; Pyridoxine; Pyrazinamide; Ethambutol; Rifabutin; Rifampin
Intervention description: Two LPV 200 mg/RTV 50 mg fixed-dose combination tablets orally twice daily from entry to Week 72.; Four LPV 200 mg/RTV 50 mg fixed-dose combination tablets orally twice daily from entry through Week 72.; One 400 mg tablet orally twice daily from entry to Week 72.; 300 mg orally once daily from entry through Week 24.; 25 mg orally once daily from entry to Week 24.; 20 to 30 mg/kg orally once daily (not to exceed 2 g per day) from entry through Week 8 study visit (or until completion of intensive TB treatment as determined after dose adjustment in accrual period 1 participants).; 15 to 20 mg/kg orally once daily from entry through Week 8 study visit (or until completion of intensive TB treatment as determined after dose adjustment in accrual period 1 participants).; 300 mg of rifabutin orally once until LPV/RTV is started; then the dose will be reduced to 150 mg daily from the start of LPV/RTV through Week 24.; Weight-based dose; for weight < 45 kg: 450 mg orally once daily; for weight > 45 kg: 600 mg orally once daily, from entry to week 24.
Intervention MeSH terms: Pyridoxine; Vitamin B 6; Ritonavir; Lopinavir; Raltegravir Potassium; Rifampin; Isoniazid; Pyrazinamide; Ethambutol; Rifabutin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 71.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      There is a rapidly-growing need to identify evidence-based, safe, and effective co-treatment
      regimens for HIV-related tuberculosis (TB) among patients who require protease inhibitor
      (PI)-based antiretroviral therapy (ART). This study compared three alternative co-treatment
      options among participants in high TB endemic resource-constrained settings, in which one
      co-treatment option explores if an additional anti-HIV drug needs to be used when patients
      are being treated with a PI together with rifabutin-based anti-TB treatment.
    

Eligibility criteria:

        Inclusion Criteria:

          -  HIV-1 infection

          -  CD4+/CD8+ T-cell count obtained within 30 days prior to study entry

          -  Confirmed or probable pulmonary or extrapulmonary TB (more information on the
             criterion can be found in the protocol)

          -  Chest x-ray within 30 days prior to study entry

          -  A PI-based antiretroviral regimen is required, as determined by the participant's
             primary clinician/clinical facility

          -  Certain laboratory values obtained within 14 days prior to study entry (more
             information on the criterion can be found in the protocol)

          -  For females of reproductive potential, negative serum or urine pregnancy test within 7
             days prior to study entry and 72 hours of starting study medications

          -  Willing to use acceptable methods of contraception while on study drugs and for 6
             weeks after stopping these drugs

          -  Karnofsky performance score > 40 within 14 days prior to study entry, and likelihood
             of survival, in the opinion of the site investigator, for at least 6 months

          -  Ability to swallow oral medications

          -  Ability and willingness of participant or legal guardian/representative to provide
             informed consent

        Exclusion Criteria:

          -  History of completed TB treatment and resolution of TB symptoms less than 1 year prior
             to the current TB episode at study entry, or incomplete treatment for a prior episode
             of TB (i.e., defaulted past TB treatment) at any time prior to the current TB episode

          -  Documented multidrug-resistant tuberculosis (MDR TB) or extensively drug-resistant
             tuberculosis (XDR TB)

          -  Participants infected with a rifamycin resistant strain of TB (more information on the
             criterion can be found in the protocol)

          -  Receipt of more than 28 cumulative days of anti-TB treatment for the current TB
             episode prior to study entry

          -  Active drug or alcohol use or dependence that, in the opinion of the site
             investigator, would interfere with adherence to study requirements

          -  Active illness requiring systemic treatment and/or hospitalization within 30 days
             prior to study entry, or that in the opinion of the site investigator, might otherwise
             interfere with adherence to study requirements

          -  Pregnant or breastfeeding

          -  Anticipated receipt of prohibited medications (more information on the criterion can
             be found in the protocol)

          -  Known intolerance/allergy/sensitivity or any hypersensitivity to components of study
             drugs or their formulations

          -  History of close contact with known MDR or XDR TB patients at any time prior to study
             entry