title: Predictors of virologic and clinical response to nevirapine versus lopinavir/ritonavir-based antiretroviral therapy in young children with and without prior nevirapine exposure for the prevention of mother-to-child HIV transmission.
abstract: BACKGROUND
  In a randomized trial comparing nevirapine (NVP)-based versus lopinavir/ritonavir (LPV/r)-based antiretroviral therapy (ART) in HIV-infected children [primary endpoint discontinuation of study treatment for any reason or virologic failure by week 24] aged 2 months to 3 years, we assessed whether clinical, virologic, immunologic and safety outcomes varied by prior single-dose NVP exposure (PrNVP) for prevention of mother-to-child HIV transmission and other covariates.
  
  
  METHODS
  Efficacy was assessed by time to ART discontinuation or virologic failure, virologic failure/death and death; safety by time to ART discontinuation because of a protocol-defined toxicity and first ≥ grade 3 adverse event; immunology and growth by changes in CD4%, weight/height World Health Organization z-scores from entry to week 48. Cox proportional hazards and linear regression models were used to test whether treatment differences depended on PrNVP exposure and other covariates.
  
  
  RESULTS
  Over a median follow up of 48 (PrNVP) and 72 (no PrNVP) weeks, there was no evidence of differential treatment effects by PrNVP exposure or any other covariates. LPV/r-based ART was superior to NVP-based ART for efficacy and safety outcomes; however, those on NVP had larger improvements in CD4%, weight and height z-scores. Lower pretreatment CD4% and higher HIV-1 RNA levels were associated with reduced efficacy, lower pretreatment CD4% with shorter time to ART discontinuation because of a protocol-defined toxicity, and no PrNVP with shorter time to first grade ≥ 3 adverse event.
  
  
  CONCLUSIONS
  Differences between LPV/r and NVP ART in efficacy, safety, immunologic and growth outcomes did not depend on PrNVP exposure, prior breast-feeding, sex, HIV-1 subtype, age, pretreatment CD4%, HIV-1 RNA or World Health Organization disease stage. This finding should be considered when selecting an ART regimen for young children.
authors.affiliation: From the *Center for Biostatistics in AIDS Research, Harvard School of Public Health, Boston, MA; †University of Witwatersrand, Perinatal HIV Research Unit, Chris Hani Baragwanath Hospital, Johannesburg, South Africa; ‡Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD; §Department of Epidemiology, ICAP, Mailman School of Public Health and College of Physicians and Surgeons, Columbia University, New York, NY; ¶Department of Paediatrics and Child Health, University of Zimbabwe College of Health Sciences, Harare, Zimbabwe; ‖Makerere University-Johns Hopkins University Research Collaboration, Kampala, Uganda; **University of North Carolina Project, Lilongwe, Malawi; ††University Teaching Hospital, Lusaka, Zambia; ‡‡Division of Paediatrics and Infectious Diseases, Tygerberg Children's Hospital, Stellenbosch University, Tygerberg; §§University of the Witwatersrand Reproductive Health and HIV Institute, Faculty of Health Sciences, Johannesburg, South Africa; ¶¶Department of Pediatrics, BJ Medical College and Sassoon General Hospital, Pune, India; ‖‖Duke University-Kilimanjaro Christian Medical Center Collaboration, Moshi, Tanzania; ***Department of Paediatrics and Child Health, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa; †††Frontier Science and Technology Research Foundation, Amherst, NY; ‡‡‡Social and Scientific Systems, Durham, NC; §§§Maternal and Pediatric Infectious Disease Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Rockville, MD; ¶¶¶HJF-DAIDS, a Division of The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Contractor to NIAID, NIH, DHHS, Bethesda, MD; and ‖‖‖Division of Infectious Diseases and International Health, Geisel School of Medicine at Dartmouth, One Medical Center Drive, Lebanon, NH.
authors.forename: Jane C
authors.initials: JC
authors.lastname: Lindsey
authors.forename: Michael D
authors.initials: MD
authors.lastname: Hughes
authors.forename: Avy
authors.initials: A
authors.lastname: Violari
authors.forename: Susan H
authors.initials: SH
authors.lastname: Eshleman
authors.forename: Elaine J
authors.initials: EJ
authors.lastname: Abrams
authors.forename: Mutsa
authors.initials: M
authors.lastname: Bwakura-Dangarembizi
authors.forename: Linda
authors.initials: L
authors.lastname: Barlow-Mosha
authors.forename: Portia
authors.initials: P
authors.lastname: Kamthunzi
authors.forename: Pauline M
authors.initials: PM
authors.lastname: Sambo
authors.forename: Mark F
authors.initials: MF
authors.lastname: Cotton
authors.forename: Harry
authors.initials: H
authors.lastname: Moultrie
authors.forename: Sandhya
authors.initials: S
authors.lastname: Khadse
authors.forename: Werner
authors.initials: W
authors.lastname: Schimana
authors.forename: Raziya
authors.initials: R
authors.lastname: Bobat
authors.forename: Bonnie
authors.initials: B
authors.lastname: Zimmer
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Petzold
authors.forename: Lynne M
authors.initials: LM
authors.lastname: Mofenson
authors.forename: Patrick
authors.initials: P
authors.lastname: Jean-Philippe
authors.forename: Paul
authors.initials: P
authors.lastname: Palumbo
mesh_terms: D017954:Africa South of the Sahara / Q000453:epidemiology; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D002675:Child, Preschool; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000453:epidemiology / Q000821:virology; D015497:HIV-1 / Q000302:isolation & purification*; D006801:Humans; D015994:Incidence; D007194:India / Q000453:epidemiology; D007223:Infant; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control*; D061466:Lopinavir / Q000627:therapeutic use*; D008297:Male; D019829:Nevirapine / Q000627:therapeutic use*; D019438:Ritonavir / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D019380:Anti-HIV Agents; D061466:Lopinavir; D019829:Nevirapine; D019438:Ritonavir