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Completed

NCT Number: NCT03800407

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

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.

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Key information

Conditions

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

Age range

3 year–14 year

Sex eligibility

All sexes

Study type

Observational

Primary location

Kwame Nkrumah University of Science and Technology

Kumasi, Ghana

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

observational study

Other

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

Primary outcomes

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

    Time frame: At week 24 of HIV therapy.

    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.

Secondary outcomes

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

    Time frame: Up to week 24 of HIV therapy.

    Relationship between EFV mid-dose concentration and HIV RNA suppression rate in the combined population of HIV-infected children with and without TB coinfection.

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

    Time frame: Up to week 24 of HIV therapy.

    Relationship poor ART adherence and EFV-based ART response in the combined population of HIV-infected children with and without TB coinfection.

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

    Time frame: Up to week 24 of HIV therapy.

    Relationship between CYP2B6 516G>T genotype status and likelihood of poor EFV-based ART adherence.

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

    Time frame: Up to week 24 of HIV therapy.

    Relationship between CYP2B6 516G>T genotype status and likelihood of HIV RNA suppression.

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

    Time frame: Up to week 48 of HIV therapy.

    Proportion of children with TB/HIV coinfection compared to those with only HIV infection with virological failure (HIV RNA > 1000 copies/mL) at 12 months of EFV-based ART.

Sponsors and collaborators

Lead sponsor

University of Florida

Other

Collaborators

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

Registry information

Official study title

Pharmacokinetics of Anti-tuberculosis and Antiretroviral Drugs in Children

Important dates

Study start
2019
Primary completion
2025
Study completion
2025
First posted
Jan 11, 2019
Registry last updated
Aug 8, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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