Determination of Adequate Tuberculosis Regimen in Patients Hospitalized With HIV-associated Severe Immune Suppression (DATURA)
Tuberculosis, HIV-1-infection, Immuno-Deficiency
About this trial
This is an interventional treatment trial for Tuberculosis focused on measuring Tuberculosis, HIV-1, Mortality, Immuno-deficiency, Isoniazid, Rifampicin
Eligibility Criteria
INCLUSION CRITERIA
- Patient (and legally designed representative of minor patient) able to correctly understand the trial and to sign the informed consent
- Aged ≥ 15 years
- Confirmed HIV-1 infection as documented at any time prior to trial entry per national HIV testing procedures
- CD4 count ≤ 100 cells/μL
Hospitalized for a newly diagnosed TB, defined by:
- Any positive Xpert® MTB/RIF specimen (sputum, urine, pus, other),
- Or a positive urine lipoarabinomannan (LAM) test,
- Or an abnormal chest X-ray compatible with active TB
EXCLUSION CRITERA
- Initiation of TB drugs for more than 3 days
- History of TB treatment during the last 6 months
- Central neurological symptoms, including but not restrictive to TB meningitis
- Suspected TB pericarditis
- Documented Mycobacterium tuberculosis strain resistant to rifampicin using rapid molecular testing (Xpert® MTB/RIF)
- Any concomitant medication or known hypersensitivity contraindicating any component of the TB treatment
- HIV-2 co-infection
- History of ART, unless if stopped for more than 1 year
- Current treatment with ART for more than 1 week
- Any contraindication to efavirenz and dolutegravir
- Severe associated diseases requiring specific treatment (including all specific AIDS defining illnesses other than TB and any severe sepsis)
- Impaired hepatic function with ALT (SGPT) > 5 times the upper limit of normal (ULN) value
- Creatinine clearance < 50 mL/min (according to the Cockcroft-Gault formula)
- Pregnancy or breastfeeding
Sites / Locations
- National Center for HIV/AIDS, Dermatology and STD (NCHADS)Recruiting
- Jamot HospitalRecruiting
- Ignace Deen HospitalRecruiting
- Mbarara Regional Referral hospitalRecruiting
- Pham Ngoc Thach Hospital
- University Teaching HospitalRecruiting
Arms of the Study
Arm 1
Arm 2
Experimental
Active Comparator
Intensified TB treatment
WHO standard TB treatment
Increased doses of rifampicin (R) to 35±5 mg/kg daily and isoniazid (H) 10±2 mg/kg daily together with standard-dose of pyrazinamide (Z) 20-30 mg/kg daily + ethambutol (E) 15-20 mg/kg daily for 8 weeks (initial phase of TB treatment). Prednisone 40 to 80 mg once a day (OD) according to weight bands for 2 weeks, followed by 20 to 40 mg OD according to weight bands for 2 weeks, then 10 to 20 mg OD according to weight bands for the last 2 weeks (total duration: 6 weeks). Because of the corticosteroid treatment, albendazole 400 mg OD will be given to participants for 3 days. Continuation phase: 16 weeks of RH.
Standard-dose of R 8-12 mg/kg daily + H 4-6 mg/kg daily + Z 20-30 mg/kg daily + E 15-20 mg/kg daily for 8 weeks. Continuation phase: 16 weeks of RH.