Standard Versus Double Dose Dolutegravir in Patients With HIV-associated Tuberculosis
Condition: HIV Infections; Tuberculosis
MeSH terms: Tuberculosis
Intervention: Placebo; Dolutegravir 50 mg
Intervention description: Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily is not given with a supplementary dose of dolutegravir 50 mg.; Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily is given with a supplementary dose of dolutegravir 50 mg.
Intervention MeSH terms: Dolutegravir
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Parallel assignment of randomised groups with stratification by ART-naïve versus first-line interrupter status
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 108.0
Sex: All
Minimum age: 18 Years
Maximum age: 110 Years
Healthy volunteers: No
Keywords: Antiretroviral therapy; Dolutegravir; Rifampicin; Tuberculosis; Drug-drug interaction

Summary:

      The investigators propose to conduct a phase 2 randomised (1:1) double-blind
      placebo-controlled trial of the dolutegravir-lamivudine-tenofovir fixed dose combination
      tablet daily with an additional 50 mg dose of dolutegravir/matching placebo taken 12 hours
      later in ART-naïve or fisrt-line interrupted HIV-infected patients on rifampicin-based
      anti-tuberculosis therapy. The hypothesis is that virologic outcomes with standard dose
      dolutegravir-based ART will be acceptable in patients on rifampicin-based anti-tuberculosis
      therapy.
    

Eligibility criteria:

        Inclusion Criteria:

          -  HIV-1 infection as documented by screening plasma HIV-1 RNA >1000 c/mL

          -  ART-naïve (short-term antiretroviral use for prevention of mother-to-child
             transmission will be allowed) or

          -  ART treatment interrupters on ART <6 months prior to interruption or virologically
             suppressed (<50 copies/mL or LDL) <6 months prior to interruption

          -  On rifampicin-based therapy for tuberculosis for <3 months

          -  CD4 counts >100 cells/µL

          -  Women of child-bearing potential willing to use adequate contraception (defined as
             either an intrauterine contraceptive device or hormonal contraception as per national
             guidelines)

        Exclusion Criteria:

          -  Pregnant/breastfeeding

          -  Estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 (calculated by the
             Modification of Diet in Renal Disease (MDRD) study)

          -  Alanine aminotransferase >3 times upper limit of normal (ULN)

          -  Allergy or intolerance to one of the drugs in regimen

          -  Concomitant medication known to significantly reduce or increase dolutegravir exposure
             (except rifampicin)

          -  Active psychiatric disease or substance abuse

          -  On treatment for active AIDS-defining condition other than tuberculosis (participants
             on maintenance therapy may be enrolled)

          -  Malignancy

          -  Any other clinical condition that in the opinion of an investigator puts the patient
             at increased risk of participating in the study.