Contributing Factors for Poor HIV Treatment Response in Children With TB/HIV Coinfection

NCT03800407 | Completed

• 3 other identifiers: IRB201801820 TB/HIV - N2R01HD0717795R01HD071779-10
• Study Type: observational
• Target: 213
• Locations: 1 country
• Sites: 1

Brief Summary

Efavirenz (EFV)-based antiretroviral therapy (ART) remains the preferred regimen in human immunodeficiency virus (HIV)-infected children aged 3 years or older on rifampin-containing antituberculosis (anti-TB) therapy. This is because drug interactions between first-line anti-TB therapy with protease inhibitors (PIs) are more severe to adjust for, and interactions with integrase strand transfer inhibitors (INSTIs) are not well studied in that age group. Although, current weight-based EFV dosing recommendation is not optimal in some children, pharmacokinetic-treatment response (PK-PD) data to guide optimal dosing of EFV during concurrent rifampin-containing therapy in children is very limited. The study team propose that EFV concentrations outside the optimal therapeutic range in children will be associated with virologic failure due to lack of efficacy because of low concentrations or increased central nervous system (CNS) toxicities from high concentrations leading to poor medication adherence. The study will determine virological suppression rates in HIV-infected children with and without TB coinfection treated with standard efavirenz-based therapy and examine the factors contributing to poor virologic response.

Conditions

Tuberculosis; Human Immunodeficiency Virus; Coinfection

Keywords

Pharmacokinetic; Concurrent antituberculosis therapy; Efavirenz; Virologic response; Children

Outcome Measures

Primary Outcomes (1)

• TB coinfection status and HIV RNA < 200 copies/mL on EFV-based ART in HIV-infected children.

  The proportion of children with TB/HIV coinfection with virological suppression (HIV RNA \< 200 copies/mL) on EFV-based ART and anti-TB therapy compared to that in children with only HIV infection on EFV-based therapy.

  At week 24 of HIV therapy.

Secondary Outcomes (5)

• Efavirenz plasma mid-dose concentration and HIV RNA suppression < 200 copies/mL.

  Up to week 24 of HIV therapy.

• Random efavirenz concentration below the limit of detection (poor ART adherence) and HIV RNA suppression rate.

  Up to week 24 of HIV therapy.

• CYP2B6 516G>T genotype status and random efavirenz concentration below the limit of detection (poor ART adherence).

  Up to week 24 of HIV therapy.

• CYP2B6 516G>T genotype status and HIV RNA suppression < 200 copies/mL.

  Up to week 24 of HIV therapy.

• TB coinfection status and risk of virological failure on EFV-based ART.

  Up to week 48 of HIV therapy.

Study Arms (2)

EFV-based ART

ART-naïve HIV-infected children aged 3 - 14 years who initiate EFV-based ART

Other: Observational study

Concurrent EFV-based ART plus anti-TB therapy

ART-naïve HIV-infected children aged 3 - 14 years with TB coinfection who initiate EFV-based ART while receiving first-line anti-TB therapy

Other: Observational study

Interventions

Observational study OTHER

Outcome of EFV-based ART in children with TB/HIV coinfection compared to those with HIV only on EFV-based ART

Concurrent EFV-based ART plus anti-TB therapy; EFV-based ART

Eligibility Criteria

• Age: 3 Years - 14 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)
• Sampling Method: Non-Probability Sample

Study Population

Children aged 3 to 14 years old with HIV infection with or without active TB

You may qualify if:

• HIV seropositive children with or without active TB
• Antiretroviral-naïve to efavirenz and meet criteria for initiation or switch to efavirenz-based ART
• Are available for follow-up until achievement of a study endpoint like completion of study at 6 months or discontinuation of ART.

You may not qualify if:

• Unable to obtain informed signed consent parent(s) or legal guardian
• Have AIDS-related opportunistic infections other than TB
• History of acute hepatitis within 30 days of study entry
• Persistent vomiting or diarrhea at time of enrolment
• Hemoglobin \< 6 g/dl, white blood cells \< 2500/mm3, serum creatinine \> 1.5 mg/dl, aspartate transaminase (AST) and alanine transaminase (ALT) \> 2 times upper limit of normal

Sponsors & Collaborators

• University of Florida: lead
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (1)

Kwame Nkrumah University of Science and Technology

Kumasi, Ghana

Location

Biospecimen

Retention: SAMPLES WITH DNA

Ethylenediaminetetraacetic acid (EDTA) plasma and whole blood DNA

MeSH Terms

Conditions

Tuberculosis; Acquired Immunodeficiency Syndrome; Coinfection

Interventions

Observation

Condition Hierarchy (Ancestors)

Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; HIV Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Methods; Investigative Techniques

Study Officials

• Awewura Kwara, MD

  University of Florida

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 3, 2019
• First Posted: January 11, 2019
• Study Start: January 28, 2019
• Primary Completion: July 31, 2025
• Study Completion: July 31, 2025
• Last Updated: August 8, 2025

Record last verified: 2025-08

Locations

GH (1)