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

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.

Figure 1

Reasons for Exclusion of Clinic Patients From the Study Cohort ^aThe patients who initiated a protease inhibitor–based treatment were enrolled in a clinical trial. A few patients began taking 2 nucleoside reverse transcriptase inhibitors before highly active antiretroviral therapy was available. ^bIncluded in death and loss to follow-up counted as virological failure subanalysis.

Figure 2

Kaplan-Meier Survival Estimate for Proportion Without Virological Failure in Total Cohort Virological failure was defined by lack of plasma HIV RNA suppression to less than 400 copies/mL by 6 months or confirmed plasma HIV RNA of 400 copies/mL or greater after suppression. Time to virological failure was the time of the 6-month viral load for those who did not achieve virological suppression by 6 months. For those with subsequent virological rebound, time to virological failure was defined as the time of the first elevated viral load after initial virological suppression.

Figure 3

Kaplan-Meier Survival Estimates for Proportion Without Virological Failure by Sex Virological failure was defined by lack of plasma HIV RNA suppression to less than 400 copies/mL by 6 months or confirmed plasma HIV RNA of 400 copies/mL or greater after suppression. Time to virological failure was the time of the 6-month viral load for those who did not achieve virological suppression by 6 months. For those with subsequent virological rebound, time to virological failure was defined as the time of the first elevated viral load after initial virological suppression.