Dolutegravir Pharmacokinetics Among HIV/TB Coinfected Children Receiving Standard and High-dose Rifampicin

NCT05069688 | Recruiting Phase 1 DMC

• 1 other identifier: 2021P002401
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Tuberculosis (TB) is the leading cause of death among children with HIV, yet insufficient data are available on the pharmacokinetics of newer HIV/TB cotreatment strategies in children. Current WHO-recommended rifampicin dosages result in low concentrations in most children, and high-dose rifampicin may improve outcomes and shorten treatment duration. Yet the impact of high-dose rifampicin on dolutegravir exposures has not been examined in children. This study aims to evaluate the safety and pharmacokinetics of dolutegravir twice daily among HIV/TB coinfected children receiving standard-dose and high-dose rifampicin.

Conditions

Pediatric HIV Infection; Tuberculosis Infection

Keywords

pharmacokinetic; dolutegravir; rifampicin

Outcome Measures

Primary Outcomes (2)

• Dolutegravir AUC during standard-dose rifampicin

  Dolutegravir area under the concentration time curve (AUC) will be compared to therapeutic ranges established in the adult and pediatric literature

  week 20

• Dolutegravir AUC during high-dose rifampicin

  Dolutegravir AUC will be compared against therapeutic ranges established in the literature and during standard-dose rifampicin

  week 22

Secondary Outcomes (3)

• Rifampicin maximum concentration (Cmax) during standard-dose rifampicin

  week 20

• Rifampicin Cmax during high-dose rifampicin

  week 22

• Proportion of participants experiencing severe (grade 3 or 4) clinical or laboratory adverse events

  Week 48

Study Arms (1)

Dolutegravir PK during standard and high-dose rifampicin

EXPERIMENTAL

This is a single arm study: all patients are started on HIV/TB cotreatment considered standard of care and then for two weeks (study weeks 20-21) high-dose rifampicin is given during which safety and pharmacokinetics are examined.

Drug: rifampicin

Interventions

rifampicin DRUG

Patients will receive standard TB and HIV treatment, however, for two weeks (study weeks 20-21) the dose of rifampicin will be increased from standard-dose to high-dose to assess pharmacokinetics and safety

Dolutegravir PK during standard and high-dose rifampicin

Eligibility Criteria

• Age: 4 Weeks - 5 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• ART-naïve or ART-experienced HIV-infected children between 4 weeks and \<6 years of age
• Active TB diagnosis
• Weight of at least 3 kilograms
• Consent of the parent or legal guardian

You may not qualify if:

• Baseline labs with evidence of ≥grade 3 abnormalities: ALT, total bilirubin, absolute neutrophil count (ANC), platelets, or creatinine
• Suspected TB meningitis or presenting with acute respiratory distress or decompensation
• Receipt of a medication that has drug-drug interactions with dolutegravir or rifampicin

Sponsors & Collaborators

• Brigham and Women's Hospital: lead
• APIN Public Health Initiatives: collaborator
• University of Cape Town: collaborator

Study Sites (1)

University College Hospital/ University of Ibadan

Ibadan, Oyo State, Nigeria

RECRUITING

MeSH Terms

Conditions

Latent Tuberculosis

Interventions

Rifampin

Condition Hierarchy (Ancestors)

Tuberculosis; Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Latent Infection

Intervention Hierarchy (Ancestors)

Rifamycins; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds

Study Officials

• Holly Rawizza, MD, MPH

  Brigham and Women's Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Holly Rawizza, MD, MPH

CONTACT

617-432-4686; hrawizza@bwh.harvard.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Model Details: Prospective single-arm, open-label, pharmacokinetic and safety study

Study Record Dates

• First Submitted: September 16, 2021
• First Posted: October 6, 2021
• Study Start: July 7, 2023
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: December 2, 2025

Record last verified: 2025-11

Locations

NG (1)