Dolutegravir Pharmacokinetics During Weekly Rifapentine/Isoniazid for TB Prevention

Latent Tuberculosis Clinical Trial

Official title: Dolutegravir Pharmacokinetics During Weekly Rifapentine/Isoniazid for TB Prevention

Status Not yet recruiting

Clinical Trial Summary

Tuberculosis (TB) is the leading cause of death among children living with HIV, yet insufficient data are available on the pharmacokinetics of newer TB prevention strategies in children. Short-course TB prevention/latent TB infection (LTBI) treatment regimens increase completion rates but have not been adequately studied among children living with HIV. Our prospective, open-label PK study will examine and extend use of weekly rifapentine and isoniazid (3HP) among children receiving dolutegravir. This will address gaps in knowledge by examining two-way PK of short-course LTBI treatment in a vulnerable pediatric population.

Clinical Trial Description

This study is a prospective, single-arm, open-label, intensive and sparse pharmacokinetic (PK) and safety study to evaluate steady-state dolutegravir (DTG) and rifapentine (RPT) concentrations among 25 ART-naïve or experienced children living with HIV who screen negative for TB in two age categories. Study design differs by age cohort since RPT dosing is well-established for children ≥2 years of age but not for children <2 years. Children 2-11 years receive standard weekly rifapentine/isoniazid (3HP) dosing for a 12-week course, a World Health Organization (WHO)-recommended LTBI treatment option. For young children <2 years of age, intensive PK will be evaluated after a single-dose of extrapolated weekly rifapentine/isoniazid (RPT/INH), followed by standard WHO-recommended LTBI prophylaxis (isoniazid daily).

Children will be recruited from two large pediatric HIV clinics in Nigeria. Children 2-11 years will receive HIV treatment that is considered standard of care consisting of weight-based DTG once daily along with two non-nucleoside reverse transcriptase inhibitors (NRTIs), plus 3HP at standard doses for LTBI treatment. Children <2 years of age also receive standard DTG-based ART as well as standard isoniazid (INH) prophylaxis for LTBI, however, they will additionally receive a single dose of weekly RPT/INH for study purposes. The primary study intervention is, therefore, additional blood sampling for drug concentration determination (both DTG and RPT) and biomarker assessment. Clinical and laboratory monitoring for toxicity occur throughout the 48 week study period.

PK sampling for drug concentration determination will occur at three time points during the 48-week study. Specifically, intensive PK sampling will occur at study week 6, while sparse PK sampling will occur at weeks 4 and 7. Additionally, the endogenous biomarker of CYP3A4 activity, 4-beta-hydroxycholesterol to cholesterol ratio, will be evaluated to advance understanding of underlying mechanisms of drug action. Blood sampling to quantify this biomarker will occur at either 4 (among ART-experienced children) or 5 (ART-naive) time points during the 48-week study. ;

Related Conditions & MeSH terms

• Latent Tuberculosis
• Pediatric HIV Infection
• Tuberculosis

• NCT number: NCT06281834
• Study type: Interventional
• Source: Brigham and Women's Hospital
• Contact: Holly Rawizza, MD, MPH
• Phone: 617-432-4686
• Email: hrawizza@bwh.harvard.edu
• Status: Not yet recruiting
• Phase: Phase 1
• Start date: May 2024
• Completion date: June 2027