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July 10, 2008

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BULLETIN
Anti-TB Drug Fails to Benefit HIV-Exposed Infants who were Unexposed to TB at Study Enrollment


Interim results from a clinical study indicate that the anti-tuberculosis (TB) drug isoniazid is safe but ineffective in preventing TB or death in infants who at the time of enrollment had no history of TB exposure or disease and were either HIV-infected or HIV-exposed but uninfected.

An independent data and safety monitoring board (DSMB) recently reached this conclusion after examining data from a large clinical trial in southern Africa. Consequently, the DSMB recommended that the infants in the study discontinue taking isoniazid or placebo and that no additional infants be enrolled in the trial, which is sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health. NIAID concurred with these recommendations.

The study staff will continue following the enrolled infants at least through each baby’s next scheduled visit but have not yet decided whether to continue follow-up beyond that point. The parents and legal guardians of the infants are being informed of these developments as rapidly as possible.

The Phase II/III efficacy trial began in December 2004. The goal was to determine whether a 96-week course of isoniazid—a key drug used to treat TB and to prevent TB disease in adults with documented TB exposure—could protect the infants of HIV-infected mothers from getting TB or dying. The trial is being conducted at three locations in South Africa and one in Botswana where the incidence rates of TB and HIV are extremely high, according to UNAIDS and the World Health Organization (WHO). TB-HIV co-infection is the leading cause of HIV-related deaths in Africa, WHO reports, and public health experts are increasingly integrating the treatment and prevention of these two diseases.

The study enrolled babies who had no history of TB exposure or disease and were either infected with HIV or exposed to HIV but uninfected. The more than 1,350 infants enrolled were assigned at random to receive either isoniazid or a placebo daily for 96 weeks beginning at 3 to 4 months of age and at least 90 days after receiving Bacille Calmette-Guerin (BCG) vaccination, the standard TB vaccine. The study’s investigators do not yet know which infants received the drug or placebo. As prophylaxis against Pneumocystis pneumonia, all HIV-infected infants also received cotrimoxazole for at least 6 months. The infants had physical exams and blood drawn at the start of the study and every 12 to 24 weeks thereafter. These exams were originally scheduled to continue for more than 3.5 years.

During a regularly scheduled interim review of study data on June 26th, the DSMB found no significant difference in the rates of TB or death in the infants who had received isoniazid compared with those who had received placebo. The DSMB also found no evidence of clinically significant differences in safety or adverse events between the two groups of babies. These findings led the DSMB to conclude that it would be futile to continue the study as originally designed.

Isoniazid remains a mainstay for preventing TB in adults, TB-exposed infants and children, and other populations even though it was ineffective at preventing TB or death in the infants in this clinical trial. The medication also remains an essential ingredient of a multi-drug TB treatment regimen.

Media inquiries can be directed to the NIAID NIAID Office of Communications at 301-402-1663, niaidnews@niaid.nih.gov.


NIAID conducts and supports research—at NIH, throughout the United States, and worldwide—to study the causes of infectious and immune-mediated diseases, and to develop better means of preventing, diagnosing and treating these illnesses. News releases, fact sheets and other NIAID-related materials are available on the NIAID Web site at www.niaid.nih.gov.

About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

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Last Updated July 10, 2008