Efavirenz (EFV) in HIV-Infected and HIV/Tuberculosis (TB) Coinfected Children

• Status: Completed
• Trial end date: 2018-02-16
• Target enrollment: 0
• Participant gender: All

Summary

Efavirenz (EFV) is an anti-HIV medicine that is commonly used to treat HIV infection in adults and children older than 3 years of age. This study is being conducted to look at the safety of EFV, blood levels of EFV, genetic factors that may affect blood levels of EFV, and how easy it is for infants and young children to take and tolerate EFV. This information will help recommend the best doses of EFV for children younger than 3 years of age.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Collaborator: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
• Treatments: Efavirenz; Rifampin

Criteria

Inclusion Criteria (Cohort I, Step 1 and Cohort II)

• Older than 3 months but younger than 36 months of age (up to but not including the 3rd birthday) at the time of enrollment

• Documentation of HIV-1 infection defined as positive results from two samples collected at different time points. More details on this criterion can be found in the protocol.

• Treatment-eligible as defined by country-specific guidelines, World Health Organization (WHO) treatment algorithm, or by clinician's determination that the participant should be treated on other clinical grounds and will initiate antiretroviral (ARV) therapy (ART) AND has determined that in-country access to ART will be available at study conclusion

• Able to swallow the contents of efavirenz (EFV) as opened capsules in food or liquid vehicle

• Parent, legal guardian, or designated guardian according to country-specific guidelines able and willing to provide signed informed consent and to have the participant followed at the clinical site

Inclusion Criteria (Cohort I, Step 2 ONLY)

• Currently enrolled in Cohort I, Step 1

• Clinically diagnosed with HIV/TB co-infection and requires rifampin-containing therapy, in the clinical judgment of the site investigator

• Chemistry and hematology laboratory values drawn during Cohort I, Step 1 are all Grade 3 or lower, except for aspartate aminotransferase/alanine aminotransferase (AST/ALT), which must be Grade 2 or lower within 4 weeks of entry into Cohort I, Step 2

Inclusion Criteria (Cohort II ONLY)

• Clinically diagnosed with HIV/TB coinfection and requires rifampin-containing therapy, in the clinical judgment of the site investigator

• Participant is tolerating a rifampin-containing anti-TB drug regimen for at least 1 week prior to study entry

• Participant plans to continue anti-TB and study treatment for at least 16 weeks from initiation of study treatment

Exclusion Criteria (Cohort I, Step 1 and Cohort II)

• Known hypersensitivity to any component of EFV capsule formulation.

• Participants with severe malnutrition defined in the protocol

• Infants/children who have previously been treated with EFV-based ART

• Infants/children younger than 24 months of age with documented receipt of nevirapine (NVP) therapy, including single dose NVP for prevention of mother-to-child transmission (PMTCT). More information on this criterion can be found in the protocol.

• Infants/children younger than 24 months of age whose mothers have documentation of receiving NVP as part of PMTCT unless they meet criteria under the exception detailed in the protocol. More information on this criterion can be found in the protocol.

• Grade 2 or higher AST or ALT at screening

• Any Grade 3 or higher laboratory toxicity at screening

• Higher than Grade 3 clinical toxicity at screening

• Participants with acute, serious infections requiring active treatment (e.g. pneumocystis pneumonia [PCP], etc.) may not enroll until judged to be clinically stable by the site investigator. Participants may enroll while completing active opportunistic infection treatment. Prophylaxis against opportunistic infections, including isoniazid, will be allowed.

• Chemotherapy for active malignancy

• Active central nervous system (CNS) infection, such as TB meningitis or cryptococcal meningitis, receiving primary therapy

• Breastfeeding infants whose mothers are receiving or plan to initiate EFV-based highly active antiretroviral therapy (HAART) before the results of the intensive pharmacokinetic (PK) studies are available will be excluded from enrollment in this study due to the potential effect on the infant's EFV PK levels that will be evaluated in the study. More information on this criterion can be found in the protocol.