Rifampin and Nevirapine Interactions in Young Children

NCT01699633 | Unknown DMC

• 2 other identifiers: PK-TBHIV02R01HD071779
• Study Type: observational
• Target: 58
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Tuberculosis; HIV

Keywords

Drug-drug interactions; Drug-gene interactions; Nevirapine; Rifampicin; children

Outcome Measures

Primary Outcomes (1)

• Area under time curve (AUC) of nevirapine

  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

  At week of 4 of HIV therapy

Secondary Outcomes (4)

• 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

  Up to week 24 of HIV therapy

• Number of children with nevirapine 12-hour post-dose concentration (C12h) < 3000 ng/mL

  Week 4 of HIV therapy

• Time to HIV-1 RNA suppression below 50 copies/mL and change in CD4 cell count from baseline

  Up to week 24 of HIV therapy

• Peak concentration (Cmax) and concentration at 12-hours (C12h) post-dose of nevirapine

  At week 4 of therapy

Eligibility Criteria

• Age: 3 Months - 35 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)
• Sampling Method: Non-Probability Sample

Study Population

Children aged 3 to 35 months with HIV infection with or without TB

You may qualify if:

• HIV seropositive children with or without active TB
• Aged 3 to 35 months old
• Antiretroviral-naïve and meet criteria for initiation of antiretroviral therapy
• Are available for follow-up until achievement of a study endpoint like completion of study or discontinuation of HAART, and/or PK sampling

You may not qualify if:

• 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.

Sponsors & Collaborators

• The Miriam Hospital: lead
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (1)

Komfo Anokye Teaching Hospital

Kumasi, Ghana

RECRUITING

Related Publications (1)

• Enimil A, Antwi S, Yang H, Dompreh A, Alghamdi WA, Gillani FS, Orstin A, Bosomtwe D, Opoku T, Norman J, Wiesner L, Langaee T, Peloquin CA, Court MH, Greenblatt DJ, Kwara A. Effect of First-Line Antituberculosis Therapy on Nevirapine Pharmacokinetics in Children Younger than Three Years Old. Antimicrob Agents Chemother. 2019 Sep 23;63(10):e00839-19. doi: 10.1128/AAC.00839-19. Print 2019 Oct.

  PMID: 31332062 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

EDTA Plasma Whole blood DNA

MeSH Terms

Conditions

Tuberculosis

Condition Hierarchy (Ancestors)

Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Study Officials

• Awewura Kwara, MD, MPH&TM

  The Miriam Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Awewura Kwara, MD, MPH&TM

CONTACT

4017932463; akwara@lifespan.org

Sampson Antwi, MBChB

CONTACT

+233265812061; antwisampson@yahoo.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 14, 2012
• First Posted: October 4, 2012
• Study Start: October 1, 2012
• Primary Completion: May 1, 2017
• Study Completion: May 1, 2017
• Last Updated: October 12, 2012

Record last verified: 2012-09

Locations

GH (1)