title: Efavirenz-Based Antiretroviral Therapy Among Nevirapine-Exposed HIV-Infected Children in South Africa: A Randomized Clinical Trial.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  Participants were randomly assigned to switch to efavirenz-based therapy (n = 150) or continue ritonavir-boosted lopinavir-based therapy (n = 148).
  
  
  METHODS
  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
  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.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT01146873.
authors.affiliation: Empilweni Services and Research Unit, Rahima Moosa Mother and Child Hospital, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Ashraf
authors.initials: A
authors.lastname: Coovadia
authors.affiliation: ICAP, Mailman School of Public Health, Columbia University, New York, New York3Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York.
authors.forename: Elaine J
authors.initials: EJ
authors.lastname: Abrams
authors.affiliation: Empilweni Services and Research Unit, Rahima Moosa Mother and Child Hospital, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Renate
authors.initials: R
authors.lastname: Strehlau
authors.affiliation: Department 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.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Shiau
authors.affiliation: Empilweni Services and Research Unit, Rahima Moosa Mother and Child Hospital, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Francoise
authors.initials: F
authors.lastname: Pinillos
authors.affiliation: Empilweni Services and Research Unit, Rahima Moosa Mother and Child Hospital, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Leigh
authors.initials: L
authors.lastname: Martens
authors.affiliation: Empilweni Services and Research Unit, Rahima Moosa Mother and Child Hospital, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Faeezah
authors.initials: F
authors.lastname: Patel
authors.affiliation: Center for HIV and STIs, National Institute for Communicable Diseases, Johannesburg, South Africa.
authors.forename: Gillian
authors.initials: G
authors.lastname: Hunt
authors.affiliation: Department of Biostatistics, Mailman School of Public Health, Columbia University, New York, New York.
authors.forename: Wei-Yann
authors.initials: WY
authors.lastname: Tsai
authors.affiliation: Department 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.
authors.forename: Louise
authors.initials: L
authors.lastname: Kuhn
mesh_terms: D000480:Alkynes; D044966:Anti-Retroviral Agents / Q000008:administration & dosage*; D048588:Benzoxazines / Q000008:administration & dosage*; D002648:Child; D002675:Child, Preschool; D003521:Cyclopropanes; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000517:prevention & control / Q000635:transmission; D006801:Humans; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control*; D061466:Lopinavir / Q000008:administration & dosage*; D008297:Male; D019829:Nevirapine / Q000008:administration & dosage*; D013019:South Africa; D019562:Viral Load
chemical_list: D000480:Alkynes; D044966:Anti-Retroviral Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D061466:Lopinavir; D019829:Nevirapine; C098320:efavirenz