HIV | Rifampin and Efavirenz Interactions in Older Children
HIV research study
What is the primary objective of this study?
Efavirenz is an essential component of HIV treatment in children aged 3 years or older on anti-tuberculosis (anti-TB) treatment. However, the appropriate efavirenz dose during anti-TB treatment remains unclear. Rifampin (an anti-TB drug) increases the activity of the drug metabolizing enzymes that breakdown efavirenz, which may lead to low blood levels of efavirenz and treatment failure during cotreatment. The drug-to-drug interactions between the HIV and anti-TB drugs also vary between individuals based on genetic factors. This study will investigate the effects of anti-TB treatment, as well as drug-gene interactions on the blood concentrations of efavirenz in children with HIV and TB infections. Such data could enhance optimization of efavirenz dosage or selection of alternate regimens in some children.
Who is eligible to participate?
Inclusion Criteria: 1. Children with active TB with or without HIV co-infection. Active TB diagnosis defined by clinical criteria consistent with active TB and/or a positive AFB smear or mycobacterial culture. 2. Aged 3 months to 14 years old 3. Are available for follow-up until completion of TB treatment and/or achievement of a study endpoint like discontinuation of therapy, and/or pharmacokinetic sampling. Exclusion Criteria: 1. Unable to obtain informed signed consent parent(s) or legal guardian 2. Have AIDS-related opportunistic infections other than TB, history of or proven acute hepatitis within 30 days of study entry, persistent vomiting, or diarrhea 3. Hemoglobin < 6 g/dl, white blood cells < 2500/mm3, serum creatinine > 1.5 mg/dl, AST and ALT > 2X upper limit of normal.
Which medical condition, disease, disorder, syndrome, illness, or injury is researched?
Interventions can include giving participants drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available or noninvasive approaches such as surveys, education, and interviews.
Research studies and clinical trials typically have two or more research arms. An arm is a group of people who receive the same treatment in the study.
Start Date: October 2012
Completed Date: May 2017
Primary Outcome: Area under time curve from time 0-24 hours(AUC0-24h) of efavirenz
Secondary Outcome: Number of children with grade 3 or 4 liver enzymes elevations compared to baseline, new onset of skin rash, nausea, vomiting or treatment modification due to drug side effects
Study sponsors, principal investigator, and references
Lead Sponsor: The Miriam Hospital
Collaborator: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)