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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Primary isoniazid prophylaxis against tuberculosis in HIV-exposed children
New England Journal of Medicine, Volume 365, No. 1, Year 2011
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Description
BACKGROUND: The dual epidemic of human immunodeficiency virus (HIV) and tuberculosis is a major cause of sickness and death in sub-Saharan Africa. We conducted a double-blind, randomized, placebo-controlled trial of preexposure isoniazid prophylaxis against tuberculosis in HIV-infected children and uninfected children exposed to HIV during the perinatal period. METHODS: We randomly assigned 548 HIV-infected and 804 HIV-uninfected infants (91 to 120 days of age) to isoniazid (10 to 20 mg per kilogram of body weight per day) or matching placebo for 96 weeks. All patients received bacille Calmette-Guérin (BCG) vaccination against tuberculosis within 30 days after birth. HIV-infected children had access to antiretroviral therapy. The primary outcome measures were tuberculosis disease and death in HIV-infected children and latent tuberculosis infection, tuberculosis disease, and death in HIV-uninfected children within 96 to 108 weeks after randomization. RESULTS: Antiretroviral therapy was initiated in 98.9% of HIV-infected children during the study. Among HIV-infected children, protocol-defined tuberculosis or death occurred in 52 children (19.0%) in the isoniazid group and 53 (19.3%) in the placebo group (P = 0.93). Among HIV-uninfected children, there was no significant difference in the combined incidence of tuberculosis infection, tuberculosis disease, or death between the isoniazid group (39 children, 10%) and the placebo group (45 children, 11%; P = 0.44). The rate of tuberculosis was 121 cases per 1000 child-years (95% confidence interval [CI], 95 to 153) among HIV-infected children as compared with 41 per 1000 child-years (95% CI, 31 to 52) among HIV-uninfected children. There were no significant differences in clinical or severe laboratory toxic effects between treatment groups. CONCLUSIONS: Primary isoniazid prophylaxis did not improve tuberculosis-disease- free survival among HIV-infected children or tuberculosis-infection-free survival among HIV-uninfected children immunized with BCG vaccine. Despite access to antiretroviral therapy, the burden of tuberculosis remained high among HIV-infected children. (Funded by the National Institutes of Health and Secure the Future; ClinicalTrials.gov number, NCT00080119.) Copyright © 2011 Massachusetts Medical Society.
Authors & Co-Authors
Madhi, Shabir A.
South Africa, Johannesburg
University of the Witwatersrand
Nachman, Sharon A.
United States, Stony Brook
Renaissance School of Medicine at Stony Brook University
Violari, Avy
South Africa, Johannesburg
University of the Witwatersrand
Kim, Soyeon
United States, Boston
Center for Biostatistics in Aids Research
Cotton, Mark Fredric
South Africa, Stellenbosch
Stellenbosch University
Bobat, Raziya A.
South Africa, Durban
University of Kwazulu-natal
Jean-Philippe, Patrick
United States, Bethesda
Henry Jackson Foundation
McSherry, George D.
United States, Hershey
Penn State College of Medicine
Mitchell, Charles D.
United States, Coral Gables
University of Miami
Statistics
Citations: 160
Authors: 9
Affiliations: 8
Identifiers
Doi:
10.1056/NEJMoa1011214
ISSN:
00284793
e-ISSN:
15334406
Research Areas
Disability
Environmental
Health System And Policy
Infectious Diseases
Maternal And Child Health
Study Design
Randomised Control Trial
Cohort Study
Case-Control Study