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Rifampin and Nevirapine Interactions in Young Children

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2012 by The Miriam Hospital
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Information provided by (Responsible Party):
The Miriam Hospital Identifier:
First received: September 14, 2012
Last updated: October 11, 2012
Last verified: September 2012
Nevirapine is the preferred nonnucleoside reverse transcriptase inhibitor (NNRTI) for treatment of HIV in children younger than 3 years old who have tuberculosis (TB) coinfection. However, there is very limited data on the drug-drug interactions between rifampin and nevirapine in children of this age group. The purpose of this study is to determine the effect of rifampin-containing anti-TB treatment on the blood levels of nevirapine in young children with HIV and TB coinfection. Also, the study will find out whether checking the genetic makeup of a child could help to determine the appropriate dose of nevirapine in the setting of concomitant anti-TB treatment.


Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Effect of Rifampin-containing Anti-TB Therapy on Nevirapine Plasma Pharmacokinetics in HIV/TB Co-infected Children < 3 Years Old

Resource links provided by NLM:

Further study details as provided by The Miriam Hospital:

Primary Outcome Measures:
  • Area under time curve (AUC) of nevirapine [ Time Frame: At week of 4 of HIV therapy ] [ Designated as safety issue: No ]
    Compare nevirapine AUC0-12h 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

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 HIV therapy ] [ Designated as safety issue: Yes ]
    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 nevirapine 12-hour post-dose concentration (C12h) < 3000 ng/mL [ Time Frame: Week 4 of HIV therapy ] [ Designated as safety issue: No ]
    Relationship between clinical factors (weight, gender, nutritional status) as well as genetic factors (CYP2B6, CYP3A4 polymorphisms) and nevirapine C12h will be investigated

  • Time to HIV-1 RNA suppression below 50 copies/mL and change in CD4 cell count from baseline [ Time Frame: Up to week 24 of HIV therapy ] [ Designated as safety issue: No ]
    Relationship between nevirapine pharmacokinetics (AUC0-12h, C12h) and time to virologic suppression as well as increase in CD4 cell count from baseline in the combined study population

  • Peak concentration (Cmax) and concentration at 12-hours (C12h) post-dose of nevirapine [ Time Frame: At week 4 of therapy ] [ Designated as safety issue: No ]
    Compare nevirapine Cmax and C12h 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

Biospecimen Retention:   Samples With DNA
EDTA Plasma Whole blood DNA

Estimated Enrollment: 58
Study Start Date: October 2012
Estimated Study Completion Date: May 2017
Estimated Primary Completion Date: May 2017 (Final data collection date for primary outcome measure)
  Show Detailed Description


Ages Eligible for Study:   3 Months to 35 Months   (Child)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Children aged 3 to 35 months with HIV infection with or without TB

Inclusion Criteria:

  1. HIV seropositive children with or without active TB
  2. Aged 3 to 35 months old
  3. Antiretroviral-naïve and meet criteria for initiation of antiretroviral therapy
  4. Are available for follow-up until achievement of a study endpoint like completion of study or discontinuation of HAART, and/or PK 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.
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01699633

Contact: Awewura Kwara, MD, MPH&TM 4017932463
Contact: Sampson Antwi, MBChB +233265812061

Komfo Anokye Teaching Hospital Recruiting
Kumasi, Ghana
Contact: Sampson Antwi, MBChB    +233265812061   
Contact: Anthony Enimil, MBChB    +233208164433   
Sponsors and Collaborators
The Miriam Hospital
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Principal Investigator: Awewura Kwara, MD, MPH&TM The Miriam Hospital
  More Information

Responsible Party: The Miriam Hospital Identifier: NCT01699633     History of Changes
Other Study ID Numbers: PK-TBHIV02  R01HD071779 
Study First Received: September 14, 2012
Last Updated: October 11, 2012
Health Authority: Ghana: Committee on Human Research

Keywords provided by The Miriam Hospital:
Drug-drug interactions
Drug-gene interactions

Additional relevant MeSH terms:
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Antibiotics, Antitubercular
Antitubercular Agents
Anti-Bacterial Agents
Anti-Infective Agents
Leprostatic Agents
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Cytochrome P-450 CYP2B6 Inducers
Cytochrome P-450 Enzyme Inducers
Cytochrome P-450 CYP2C8 Inducers
Cytochrome P-450 CYP2C19 Inducers
Cytochrome P-450 CYP2C9 Inducers
Cytochrome P-450 CYP3A Inducers
Reverse Transcriptase Inhibitors
Anti-Retroviral Agents
Antiviral Agents
Anti-HIV Agents processed this record on October 25, 2016