Rifampin and Efavirenz Interactions in Older Children
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government.
Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01704144
Recruitment Status : Unknown
Verified September 2012 by The Miriam Hospital. Recruitment status was: Recruiting
First Posted : October 11, 2012
Last Update Posted : October 17, 2012
The Miriam Hospital
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
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.
Area under time curve from time 0-24 hours(AUC0-24h) of efavirenz [ Time Frame: At week of 4 of HIV therapy ]
Compare efavirenz AUC0-24h between HIV-infected children without TB and those with TB on rifampin-containing anti-TB therapy in co-infected patients
Secondary Outcome Measures :
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 [ Time Frame: up to week 24 of therapy ]
Compare frequency of adverse events as a measure of safety and tolerability between HIV-infected children with and without TB coinfection
Number of children with efavirenz 24-hour post-dose concentration (C24h) < 1000 ng/mL [ Time Frame: At week 4 of therapy ]
Relationship between clinical factors (weight, gender, nutritional status) as well as genetic factors (CYP2B6 516G>T, as well as CYP3A4, ABCB1, CAR and PXR polymorphisms) and efavirenz AUC0-24h and efavirenz C24h will be investigated
Number of children who discontinue efavirenz therapy due to drug side effects [ Time Frame: Up to week 24 of HIV therapy ]
Relationship between clinical factors (weight, gender, nutritional status) as well as genetic factors (CYP2B6 polymorphisms) and treatment modification due to drug side effects in the combined study population
Trough concentration (C24h) of efavirenz [ Time Frame: At week 4 of therapy ]
Compare efavirenz C24h between HIV-infected children without TB and those with TB, as well as in the absence of and presence of rifampin-containing anti-TB therapy in co-infected patients
AUC, Cmax and clearance of efavirenz on and off rifampin-containing anti-Tb therapy in HIV/TB co-infected patients [ Time Frame: at week 24 of therapy ]
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Ages Eligible for Study:
3 Years to 14 Years (Child)
Sexes Eligible for Study:
Accepts Healthy Volunteers:
HIV-infected children with and with TB aged 3 to 14 years old
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.
Aged 3 months to 14 years old
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.
Unable to obtain informed signed consent parent(s) or legal guardian
Have AIDS-related opportunistic infections other than TB, history of or proven acute hepatitis within 30 days of study entry, persistent vomiting, or diarrhea
Hemoglobin < 6 g/dl, white blood cells < 2500/mm3, serum creatinine > 1.5 mg/dl, AST and ALT > 2X upper limit of normal.