Jane C Lindsey1, Michael D Hughes, Avy Violari, Susan H Eshleman, Elaine J Abrams, Mutsa Bwakura-Dangarembizi, Linda Barlow-Mosha, Portia Kamthunzi, Pauline M Sambo, Mark F Cotton, Harry Moultrie, Sandhya Khadse, Werner Schimana, Raziya Bobat, Bonnie Zimmer, Elizabeth Petzold, Lynne M Mofenson, Patrick Jean-Philippe, Paul Palumbo. 1. 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.
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.
RCT Entities:
BACKGROUND: In a randomized trial comparing nevirapine (NVP)-based versus lopinavir/ritonavir (LPV/r)-based antiretroviral therapy (ART) in HIV-infectedchildren [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.
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