IMPORTANCE:
Advantages
of using efavirenz as part of treatment for children infected with human
immunodeficiency virus (HIV) include once-daily dosing, simplification of
co-treatment for tuberculosis, preservation of ritonavir-boosted lopinavir for
second-line treatment, and harmonization of adult and pediatric treatment
regimens. However, there have been concerns about possible reduced viral
efficacy of efavirenz in children exposed to nevirapine for prevention of
mother-to-child transmission.
OBJECTIVE:
To
evaluate whether nevirapine-exposed children achieving initial viral
suppression with ritonavir-boosted lopinavir-based therapy can transition to
efavirenz-based therapy without risk of viral failure.
DESIGN, SETTING, AND PARTICIPANTS:
Randomized,
open-label noninferiority trial conducted at Rahima Moosa Mother and Child
Hospital, Johannesburg, South Africa, from June 2010 to December 2013,
enrolling 300 HIV-infected children exposed to nevirapine for prevention of
mother-to-child transmission who were aged 3 years or older and had plasma HIV
RNA of less than 50 copies/mL during ritonavir-boosted lopinavir-based therapy;
298 were randomized and 292 (98%) were followed up to 48 weeks after
randomization.
INTERVENTIONS:
Participants
were randomly assigned to switch to efavirenz-based therapy (n = 150) or
continue ritonavir-boosted lopinavir-based therapy (n = 148).
MAIN OUTCOMES AND MEASURES:
Risk
difference between groups in (1) viral rebound (ie, ≥1 HIV RNA measurement of
>50 copies/mL) and (2) viral failure (ie, confirmed HIV RNA >1000
copies/mL) with a noninferiority bound of -0.10. Immunologic and clinical
responses were secondary end points.
RESULTS:
The
Kaplan-Meier probability of viral rebound by 48 weeks was 0.176 (n = 26) in the
efavirenz group and 0.284 (n = 42) in the ritonavir-boosted lopinavir group.
Probabilities of viral failure were 0.027 (n = 4) in the efavirenz group and
0.020 (n = 3) in the ritonavir-boosted lopinavir group. The risk difference for
viral rebound was 0.107 (1-sided 95% CI, 0.028 to ∞) and for viral failure was
-0.007 (1-sided 95% CI, -0.036 to ∞). We rejected the null hypothesis that
efavirenz is inferior to ritonavir-boosted lopinavir (P < .001) for both end
points. By 48 weeks, CD4 cell percentage was 2.88% (95% CI, 1.26%-4.49%) higher
in the efavirenz group than in the ritonavir-boosted lopinavir group.
CONCLUSIONS AND RELEVANCE:
Among
HIV-infected children exposed to nevirapine for prevention of mother-to-child
transmission and with initial viral suppression with ritonavir-boosted lopinavir-based
therapy, switching to efavirenz-based therapy compared with continuing
ritonavir-boosted lopinavir-based therapy did not result in significantly
higher rates of viral rebound or viral failure. This therapeutic approach may
offer advantages in children such as these.
- 1Empilweni Services and Research Unit, Rahima Moosa Mother and Child Hospital, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
- 2ICAP, Mailman School of Public Health, Columbia University, New York, New York3Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York.
- 3Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York4Gertrude H. Sergievsky Center, College of Physicians and Surgeons, Columbia University, New York, New York.
- 4Center for HIV and STIs, National Institute for Communicable Diseases, Johannesburg, South Africa.
- 5Department of Biostatistics, Mailman School of Public Health, Columbia University, New York, New York.
