Pharmacokinetics and Safety of Double-dose Dolutegravir When Used With Rifapentine for HIV-associated Tuberculosis

Prior treatment

• Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.
• Requirement for ongoing use of drugs that are known to have significant drug-drug interactions with DTG or RPT.
• Previous treatment for active TB disease within 6 months preceding initiation of study drugs.
• At the time of study entry, documentation of an M. tuberculosis isolate from the current or previous treatment episode known to be resistant to RIF or INH.

Other illness

• Known allergy/sensitivity or any hypersensitivity to components of the study drugs, or their formulations.
• Known history of acute intermittent porphyria.
• Known cirrhosis, a history of decompensated liver disease (ascites, hepatic encephalopathy, or esophageal varices).
• Documentation of severe opportunistic infections, in the opinion of the site investigator, within 3 months of study entry.

Lab values

• Known history of prolonged QT syndrome.

Other

• Breastfeeding, pregnant, or plans to become pregnant.
• More than 5 days of treatment directed against active TB for the current TB episode preceding study entry.
• Documentation of severe extra-pulmonary TB (e.g., meningitis, osteomyelitis, disseminated TB) at the time of screening.
• Acute gout at the time of screening.

• Weight ≥40 kg.
• Ability and willingness of participant or legal guardian/representative to provide informed consent.
• Documentation of HIV-1 status.
• CD4+ cell count ≥50 cells/mm3 obtained within 30 days prior to study entry at any network-approved non-US laboratory that is IQA certified.
• ART-naïve or not on ART for 12 consecutive weeks prior to TB diagnosis.
• Willingness and eligibility to start DTG-based ART at 6 weeks, with a window of ±1 week, after starting TB treatment, with no intention to change ART for the duration of the study.
• Documentation of pulmonary TB.
• Willingness to start 2HPZM/2HPM therapy for DS-TB.
• The following laboratory values obtained within 30 days prior to study entry:
  • Absolute neutrophil count (ANC) \>750 cells/mm3
  • Hemoglobin ≥7.4 g/dL
  • Platelet count ≥50,000/mm3
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) \<2.5 X the upper limit of normal (ULN)
  • Alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \[SGPT\]) \<2.5 x ULN
  • Total bilirubin ≤1.5 x ULN
  • Creatinine \<1.3 x ULN
• For participants who can become pregnant, negative serum or urine pregnancy test at screening within 30 days prior to entry and within 48 hours prior to entry.
• Participants who can become pregnant must agree not to participate in the conception process and if participating in sexual activity that could lead to pregnancy, must agree to use one reliable nonhormonal method of contraception.
• Documentation of Karnofsky performance score ≥50 within 30 days prior to entry.