Standard Versus Double Dose Dolutegravir in Patients With HIV-associated Tuberculosis: a Phase 2 Non-comparative Randomised Controlled Trial

CIDRI003

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.

2019-12-19

2022-01-20

2022-06-28

Completed

Early phase I

108

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.

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE2'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'PARALLEL', 'interventionModelDescription': 'Parallel assignment of randomised groups with stratification by ART-naïve versus first-line interrupter status', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'TRIPLE', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR']}}, 'enrollmentInfo': {'count': 108, 'type': 'ACTUAL'}}

2023-09-18