Early antiretroviral therapy and mortality among HIV-infected infants

N Engl J Med. 2008 Nov 20;359(21):2233-44. doi: 10.1056/NEJMoa0800971.


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.)

Publication types

  • Clinical Trial, Phase III
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-HIV Agents / administration & dosage*
  • Anti-HIV Agents / adverse effects
  • CD4 Lymphocyte Count
  • Disease Progression
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Female
  • Follow-Up Studies
  • HIV Infections / drug therapy*
  • HIV Infections / mortality
  • HIV-1*
  • Humans
  • Infant
  • Infectious Disease Transmission, Vertical
  • Lamivudine / administration & dosage
  • Lamivudine / adverse effects
  • Lopinavir
  • Male
  • Pyrimidinones / administration & dosage
  • Pyrimidinones / adverse effects
  • Ritonavir / administration & dosage
  • Ritonavir / adverse effects
  • Treatment Failure
  • Zidovudine / administration & dosage
  • Zidovudine / adverse effects


  • Anti-HIV Agents
  • Pyrimidinones
  • Lopinavir
  • Lamivudine
  • Zidovudine
  • Ritonavir

Associated data

  • ClinicalTrials.gov/NCT00102960