E-DRUG: A South African-UK trial on HIV-infected infants
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Dear colleagues,
link to full paper and abstract below from this week's NEJM
Valeria
http://content.nejm.org/cgi/content/full/359/21/2233?query=TOC
NEJM: Volume 359:2233-2244 November 20, 2008 Number 21
Early Antiretroviral Therapy and Mortality among HIV-Infected Infants
Avy Violari, F.C.Paed., Mark F. Cotton, M.Med., Ph.D., Diana M. Gibb,
M.D., Abdel G. Babiker, Ph.D., Jan Steyn, M.Sc., Shabir A. Madhi,
F.C.Paed., Ph.D., Patrick Jean-Philippe, M.D., James A. McIntyre,
F.R.C.O.G., for the CHER Study Team
ABSTRACT
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 [ClinicalTrials.gov] .)
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Dr Valeria Frighi
University Dept. of Psychiatry
Neurosciences Building
Warneford Hospital
Oxford
OX3 7JX
UK
Valeria.Frighi@psych.ox.ac.uk
Tel. -44 -1865 -223779
Fax -44 -1865 251076
Mobile phone 07974920013