Early Antiretroviral Therapy and Mortality among HIV-Infected Infants

Bibliographic Data

ID23328862
AuthorsAvy Violari (0000-0002-9437-776X, University of the Witwatersrand), Mark F Cotton (0000-0003-2559-6034, Stellenbosch University), Diana M Gibb (0000-0002-9738-5490, Medical Research Council), Abdel G Babiker (0000-0003-4711-3021, Medical Research Council), Jan Steyn (0000-0002-0896-8492, University of the Witwatersrand), Shabir A Madhi (0000-0002-7629-0636, University of the Witwatersrand), Patrick Jean‐Philippe (National Institutes of Health), Patrick Jean-Philippe, James Mcintyre (0000-0002-9150-1059, University of the Witwatersrand), James A McIntyre
Year2008
Volume359
Issue21
Pages2233-2244
Publication date2008-11-20
Peer ReviewedYes
Open AccessNo
TypeARTICLE
VenueNew England Journal of Medicine (JOURNAL)
Journal identifiersISSN: 0028-4793 • E-ISSN: 1533-4406
PublisherMassachusetts Medical Society (PUBLISHER • US)
DOI10.1056/nejmoa0800971
PMID19020325
PMCIDPMC2950021
OpenAlexW2122986037
LanguageEN
Citations received55
References cited19

BACKGROUND: In countries with a high seroprevalence of human immunodeficiency virus type 1 (HIV-1), HIV infection contributes significantly to infant mortality. We investigated antiretroviral-treatment strategies in the Children with HIV Early Antiretroviral Therapy (CHER) trial. METHODS: HIV-infected infants 6 to 12 weeks of age with a CD4 lymphocyte percentage (the CD4 percentage) of 25% or more were randomly assigned to receive antiretroviral therapy (lopinavir-ritonavir, zidovudine, and lamivudine) when the CD4 percentage decreased to less than 20% (or 25% if the child was younger than 1 year) or clinical criteria were met (the deferred antiretroviral-therapy group) or to immediate initiation of limited antiretroviral therapy until 1 year of age or 2 years of age (the early antiretroviral-therapy groups). We report the early outcomes for infants who received deferred antiretroviral therapy as compared with early antiretroviral therapy. RESULTS: At a median age of 7.4 weeks (interquartile range, 6.6 to 8.9) and a CD4 percentage of 35.2% (interquartile range, 29.1 to 41.2), 125 infants were randomly assigned to receive deferred therapy, and 252 infants were randomly assigned to receive early therapy. After a median follow-up of 40 weeks (interquartile range, 24 to 58), antiretroviral therapy was initiated in 66% of infants in the deferred-therapy group. Twenty infants in the deferred-therapy group (16%) died versus 10 infants in the early-therapy groups (4%) (hazard ratio for death, 0.24; 95% confidence interval [CI], 0.11 to 0.51; P<0.001). In 32 infants in the deferred-therapy group (26%) versus 16 infants in the early-therapy groups (6%), disease progressed to Centers for Disease Control and Prevention stage C or severe stage B (hazard ratio for disease progression, 0.25; 95% CI, 0.15 to 0.41; P<0.001). Stavudine was substituted for zidovudine in four infants in the early-therapy groups because of neutropenia in three infants and anemia in one infant; no drugs were permanently discontinued. After a review by the data and safety monitoring board, the deferred-therapy group was modified, and infants in this group were all reassessed for initiation of antiretroviral therapy. CONCLUSIONS: Early HIV diagnosis and early antiretroviral therapy reduced early infant mortality by 76% and HIV progression by 75%. (ClinicalTrials.gov number, NCT00102960.)

Antibody · ANTIRETROVIRAL AGENTS · Antiretroviral therapy · Antiretroviral treatment · Human immunodeficiency virus (HIV) · Serology · Seroprevalence · Sida · Viral disease · Viral load · HIV-related health complications and treatments · HIV/AIDS drug development and treatment · HIV/AIDS Research and Interventions · Immunology · Medicine · Virology · Pediatrics