title: Nevirapine- Versus Lopinavir/Ritonavir-Based Antiretroviral Therapy in HIV-Infected Infants and Young Children: Long-term Follow-up of the IMPAACT P1060 Randomized Trial.
abstract: The International Maternal Pediatric Adolescent AIDS Clinical Trials Network (IMPAACT) P1060 study demonstrated short-term superiority of lopinavir/ritonavir (LPV/r) over nevirapine (NVP) in antiretroviral therapy (ART), regardless of prior NVP exposure. However, NVP-based ART had a marginal benefit in CD4 percentage (CD4%) and growth. We compared 5-year outcomes from this clinical trial.
  
  
  
  Human immunodeficiency virus (HIV)-infected, ART-eligible children were enrolled into 2 cohorts based on prior NVP exposure and randomized to NVP- or LPV/r-based ART. The data safety monitoring board recommended unblinding results in both cohorts due to superiority of LPV/r for the primary endpoint: stopping randomized treatment, virologic failure (VF), or death by 6 months. Participants were offered a switch in regimens (if on NVP) and continued observational follow-up. We compared time to VF or death, death, and CD4% and growth changes using intention-to-treat analyses. Additionally, inverse probability weights were used to account for treatment switching and censoring.
  
  
  
  As of September 2014, 329 of the 451 (73%) enrolled participants were still in follow-up (median, 5.3 years; interquartile range [IQR], 4.3-6.4), with 52% on NVP and 88% on LPV/r as originally randomized. NVP arm participants had significantly higher risk of VF or death (adjusted hazard ratio [aHR], 1.90; 95% confidence interval [CI], 1.37-2.65) but not death alone (aHR, 1.65; 95% CI, .72-3.76) compared with participants randomized to LPV/r. Mean CD4% was significantly higher in the NVP arm up to 1 year after ART initiation, but not beyond. Mean weight-for-age z scores were marginally higher in the NVP arm, but height-for-age z scores did not differ. Similar trends were observed in sensitivity analyses.
  
  
  
  These findings support the current World Health Organization recommendation of LPV/r in first-line ART regimens for HIV-infected children.
  
  
  
  NCT00307151.
authors.affiliation: Makerere University-Johns Hopkins University Research Collaboration, Kampala, Uganda.
authors.forename: Linda
authors.initials: L
authors.lastname: Barlow-Mosha
authors.affiliation: Harvard T. H. Chan School of Public Health, Boston, Massachusetts.
authors.forename: Konstantia
authors.initials: K
authors.lastname: Angelidou
authors.affiliation: Harvard T. H. Chan School of Public Health, Boston, Massachusetts.
authors.forename: Jane
authors.initials: J
authors.lastname: Lindsey
authors.affiliation: University of KwaZulu-Natal, Durban.
authors.forename: Moherndran
authors.initials: M
authors.lastname: Archary
authors.affiliation: Stellenbosch University, Tygerberg.
authors.forename: Mark
authors.initials: M
authors.lastname: Cotton
authors.affiliation: Perinatal HIV Research Unit.
authors.forename: Sylvia
authors.initials: S
authors.lastname: Dittmer
authors.affiliation: Wits Reproductive Health and HIV Institute, Johannesburg, South Africa.
authors.forename: Lee
authors.initials: L
authors.lastname: Fairlie
authors.affiliation: Makerere University-Johns Hopkins University Research Collaboration, Kampala, Uganda.
authors.forename: Enid
authors.initials: E
authors.lastname: Kabugho
authors.affiliation: UNC Project-Malawi, Lilongwe.
authors.forename: Portia
authors.initials: P
authors.lastname: Kamthunzi
authors.affiliation: B. J. Government Medical College, Pune, India.
authors.forename: Arti
authors.initials: A
authors.lastname: Kinikar
authors.affiliation: University of Zimbabwe-University of California, San Francisco Collaborative Research Programme, Harare, Zimbabwe.
authors.forename: Tapiwa
authors.initials: T
authors.lastname: Mbengeranwa
authors.affiliation: Kilimanjaro Christian Medical College, Moshi, Tanzania.
authors.forename: Levina
authors.initials: L
authors.lastname: Msuya
authors.affiliation: University Teaching Hospital, Lusaka, Zambia.
authors.forename: Pauline
authors.initials: P
authors.lastname: Sambo
authors.affiliation: Harvard T. H. Chan School of Public Health, Boston, Massachusetts.
authors.forename: Kunjal
authors.initials: K
authors.lastname: Patel
authors.affiliation: Children's Hospital Colorado, Aurora.
authors.forename: Emily
authors.initials: E
authors.lastname: Barr
authors.affiliation: HJF-DAIDS, Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, Maryland.
authors.forename: Patrick
authors.initials: P
authors.lastname: Jean-Phillipe
authors.affiliation: Perinatal HIV Research Unit.
authors.forename: Avy
authors.initials: A
authors.lastname: Violari
authors.affiliation: Elizabeth Glaser Pediatric AIDS Foundation, Washington, District of Columbia.
authors.forename: Lynne
authors.initials: L
authors.lastname: Mofenson
authors.affiliation: Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire.
authors.forename: Paul
authors.initials: P
authors.lastname: Palumbo
authors.affiliation: University of North Carolina at Chapel Hill.
authors.forename: Benjamin H
authors.initials: BH
authors.lastname: Chi
mesh_terms: D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D006801:Humans; D007223:Infant; D053208:Kaplan-Meier Estimate; D061466:Lopinavir / Q000627:therapeutic use*; D008297:Male; D019829:Nevirapine / Q000627:therapeutic use*; D019438:Ritonavir / Q000627:therapeutic use*; D012720:Severity of Illness Index; D017211:Treatment Failure; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D061466:Lopinavir; D019829:Nevirapine; D019438:Ritonavir
keywords: HIV/AIDS; antiretroviral therapy; long-term follow-up; pediatrics