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

NCT ID: NCT03800407

Last Updated: 2025-08-08

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 213 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2019-01-28
• Study Completion Date: 2025-07-31

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.

Detailed Description

In a previous study, the study team found that first-line anti-TB therapy had minimal effect on EFV pharmacokinetics (PK) at the population level, but children with TB/HIV coinfection on anti-TB therapy had a trend towards worse virologic outcome compared to those with only HIV infection. Due to the small sample size, the study team were unable to examined the patient factors contributing to the poor virologic response. The study team hypothesized that virologic suppression rates on EFV-based therapy is significantly lower in children with TB/HIV coinfection compared to those with HIV alone. In addition, virologic response will be dependent EFV plasma concentrations, CYP2B6 516 G>T genotype and/or adherence level. This hypothesis is based on the premise that extremes (low and high EFV concentration, respectively) could lead to virologic failure because of lack of efficacy or intolerable side effects leading to poor adherence. The current study will investigate the effect of anti-TB therapy, CYP2B6 genotype and pharmacokinetically determined adherence level on virologic response in children with TB/HIV coinfection treated with EFV-based ART.

Conditions

Tuberculosis; Human Immunodeficiency Virus; Coinfection

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

EFV-based ART

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

Observational study

Intervention Type: 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

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

Observational study

Intervention Type: OTHER

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

Interventions

Observational study

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

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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

• Minimum Eligible Age: 3 Years
• Maximum Eligible Age: 14 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

NIH

Sponsor Role: collaborator

University of Florida

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Awewura Kwara, MD

Role: PRINCIPAL_INVESTIGATOR

University of Florida

Locations

Kwame Nkrumah University of Science and Technology

Kumasi, , Ghana

Countries

Ghana

Other Identifiers

2R01HD071779

Identifier Type: NIH

Identifier Source: secondary_id

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5R01HD071779-10

Identifier Type: NIH

Identifier Source: secondary_id

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IRB201801820 TB/HIV - N

Identifier Type: -

Identifier Source: org_study_id