Association between efavirenz-based compared with nevirapine-based antiretroviral regimens and virological failure in HIV-infected children.

TitleAssociation between efavirenz-based compared with nevirapine-based antiretroviral regimens and virological failure in HIV-infected children.
Publication TypeJournal Article
Year of Publication2013
AuthorsLowenthal ED, Ellenberg JH, Machine E, Sagdeo A, Boiditswe S, Steenhoff AP, Rutstein RM, Anabwani GM, Gross R
JournalJAMA
Volume309
Issue17
Pagination1803-9
Date Published2013 May 1
ISSN1538-3598
KeywordsAdolescent, Anti-Retroviral Agents, Benzoxazines, Botswana, Child, Child, Preschool, Cohort Studies, Drug Therapy, Combination, Female, HIV Infections, Humans, Male, Nevirapine, Regression Analysis, Retrospective Studies, RNA, Viral, Treatment Failure, Viral Load
Abstract

IMPORTANCE: Worldwide, the nonnucleoside reverse transcriptase inhibitors (NNRTIs) efavirenz and nevirapine are commonly used in first-line antiretroviral regimens in both adults and children with human immunodeficiency virus (HIV) infection. Data on the comparative effectiveness of these medications in children are limited.

OBJECTIVE: To investigate whether virological failure is more likely among children who initiated 1 or the other NNRTI-based HIV treatment.

DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study of children (aged 3-16 years) who initiated efavirenz-based (n = 421) or nevirapine-based (n = 383) treatment between April 2002 and January 2011 at a large pediatric HIV care setting in Botswana.

MAIN OUTCOMES AND MEASURES: The primary outcome was time from initiation of therapy to virological failure. Virological failure was defined as lack of plasma HIV RNA suppression to less than 400 copies/mL by 6 months or confirmed HIV RNA of 400 copies/mL or greater after suppression. Cox proportional hazards regression analysis compared time to virological failure by regimen. Multivariable Cox regression controlled for age, sex, baseline immunologic category, baseline clinical category, baseline viral load, nutritional status, NRTIs used, receipt of single-dose nevirapine, and treatment for tuberculosis.

RESULTS: With a median follow-up time of 69 months (range, 6-112 months; interquartile range, 23-87 months), 57 children (13.5%; 95% CI, 10.4%-17.2%) initiating treatment with efavirenz and 101 children (26.4%; 95% CI, 22.0%-31.1%) initiating treatment with nevirapine had virological failure. There were 11 children (2.6%; 95% CI, 1.3%-4.6%) receiving efavirenz and 20 children (5.2%; 95% CI, 3.2%-7.9%) receiving nevirapine who never achieved virological suppression. The Cox proportional hazard ratio for the combined virological failure end point was 2.0 (95% CI, 1.4-2.7; log rank P < .001, favoring efavirenz). None of the measured covariates affected the estimated hazard ratio in the multivariable analyses.

CONCLUSIONS AND RELEVANCE: Among children aged 3 to 16 years infected with HIV and treated at a clinic in Botswana, the use of efavirenz compared with nevirapine as initial antiretroviral treatment was associated with less virological failure. These findings may warrant additional research evaluating the use of efavirenz and nevirapine for pediatric patients.

DOI10.1001/jama.2013.3710
Alternate JournalJAMA
PubMed ID23632724
PubMed Central IDPMC3748602
Grant ListK23 MH095669 / MH / NIMH NIH HHS / United States
K23 MH095669 / MH / NIMH NIH HHS / United States
P30 AI 045008 / AI / NIAID NIH HHS / United States
P30 AI045008 / AI / NIAID NIH HHS / United States
T32 HP10026 / / PHS HHS / United States