Standard Versus Double Dose Dolutegravir in Patients With HIV-associated Tuberculosis

• Status: Recruiting
• Trial end date: 2022-08-31
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Cape Town
• Collaborators: Medecins Sans Frontieres, Netherlands; Wellcome Trust
• Treatments: Dolutegravir; Lamivudine; Tenofovir

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.