Evaluating the effectiveness of Dolutegravir in treating HIV and TB together

Efficacy, Safety and Pharmacokinetics of Dolutegravir 50 Mg Once Daily with Food Versus Dolutegravir 50 Mg Twice Daily in HIV/TB Co-infected Patients Receiving Rifampin-based Antituberculosis Therapy

This study is testing the best dose of a medication called Dolutegravir for people who have both HIV and tuberculosis to see how safe and effective it is.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 200 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: The HIV Netherlands Australia Thailand Research Collaboration (Academic / other)
• Locations: 10 sites (Bangkok, Bangkok and 9 other locations)
• Trial ID: NCT03731559 on ClinicalTrials.gov

What this trial studies

This Phase II trial aims to determine the optimal dose of Dolutegravir (DTG) for patients co-infected with HIV and tuberculosis (TB) receiving rifampicin-based therapy. The study will involve approximately 200 ART-naïve individuals diagnosed with pulmonary, pleural, or lymph node TB, assessing the safety, tolerability, and pharmacokinetics of two different dosing regimens of DTG. The trial consists of two stages, with the first stage focusing on a smaller group to evaluate safety and pharmacokinetics before proceeding to a larger cohort in the second stage if initial results are favorable.

Who should consider this trial

Good fit: Ideal candidates include adults over 18 years old who are HIV positive, ART-naïve, and diagnosed with rifampicin-sensitive TB.

Not a fit: Patients with a history of HIV treatment failure, previous TB treatment, or those currently using immunosuppressive agents may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to improved treatment options for patients co-infected with HIV and TB, enhancing their health outcomes.

How similar studies have performed: Other studies have shown promise in using Dolutegravir for HIV treatment, but this specific combination with rifampicin in TB co-infection is a novel approach.

Eligibility criteria

Inclusion Criteria:

1. documented HIV positive
2. Aged \>18 years
3. ARV naïve (previous exposure to ARV for \< 2 weeks)
4. Any CD4 cell count
5. ALT \<5 times ULN
6. estimated GFR\>60 ml/min/1.73m2
7. Hemoglobin \>7 mg/L
8. TB is diagnosed and there is a plan to receive stable doses of RIF containing anti-TB therapy for at least another 4 week period after initiation of ART
9. No other active OI (CDC class C event) except oral candidiasis or disseminated MAC
10. Body weight \>40kg
11. Able to provide written informed consent

Exclusion Criteria:

1. Have documented history of HIV treatment failure or HIV mutation to NRTI, NNRTI, and/or INIs
2. Have previously treated for tuberculosis
3. Currently using immunosuppressive agents.
4. Currently using any prohibited medications that can affect the pharmacokinetics of the study drug such as phenobarbital, and carbamazepine
5. Currently using alcohol or illicit substances that may affect the conduct of the trial as per the opinion of the site Principal Investigator
6. Unlikely to be able to remain in the follow-up period as defined by the protocol
7. Patients with proven or suspected acute hepatitis. Patients with chronic viral hepatitis are eligible provided ALT, AST \< 5 x ULN.
8. Have Karnofsky performance score \<30%
9. Have TB meningitis, bone/joints (due to prolonged use of anti-TB drug)
10. Pregnant or breastfeeding

Where this trial is running

Bangkok, Bangkok and 9 other locations

• Klang Hospital — Bangkok, Bangkok, Thailand (Recruiting)
• Bhumibol Adulyadej Hospital — Bangkok, Bangkok, Thailand (Recruiting)
• Infectious Disease, Chulalongkorn University — Bangkok, Bangkok, Thailand (Recruiting)
• Infectious Disease Taksin Hospital — Bangkok, Bangkok, Thailand (Recruiting)
• Infectious Disease Chonburi Hospital — Chon Buri, Changwat Chon Buri, Thailand (Recruiting)
• Bamrasnaradura Infectious Diseases Institute — Nonthaburi, Changwat Nonthaburi, Thailand (Recruiting)
• Infectious Disease Buddhachinaraj Phitsanulok Hospital — Phitsanulok, Changwat Phitsanulok, Thailand (Recruiting)
• Infectious Disease Chiangrai Prachanukroh Hospital — Chiang Rai, Chiangrai, Thailand (Recruiting)
• Chest Division, Faculty of Medicine, Chulalongkorn University — Bangkok, Thailand (Recruiting)
• HIV-NAT, Thai Red Cross - AIDS Research Centre — Bangkok, Thailand (Recruiting)

Study contacts

• Principal investigator: Anchalee Avihingsanon, MD, PhD — Thai Red Cross AIDS Research Centre
• Study coordinator: June Ohata, BS

Conditions HIV/TB Coinfection; Efficacy; safety; pharmacokinetics; Dolutegravir; HIV/TB co-infected patients; rifampin-based antituberculosis therapy