TB Prophylaxis Unnecessary In HIV-Infected People With Anergy, Study Suggests

National Institute of Allergy and, Infectious DiseasesEMBARGOED FOR RELEASE, Wednesday, July 30, 1997, 5:00 PM Eastern Time, John Bowersox, [email protected]

HIV-infected patients at high risk for tuberculosis (TB) but without confirmed TB infection do not benefit from preventive treatment with a front-line TB drug, a study supported by the National Institute of Allergy and Infectious Diseases (NIAID) has found. The study is reported in the July 31, 1997 issue of The New England Journal of Medicine.

"Clinicians who care for people with HIV/AIDS should take note of this important finding," says NIAID Director Anthony S. Fauci, M.D. "This study suggests that we can make more efficient use of TB prevention resources by focusing on HIV-infected persons with known TB infection or who have close contact with another individual with active TB."

Although only 10 percent of healthy people infected with TB bacteria ever develop active TB disease, co-infection with TB and HIV dramatically increases this risk. A number of studies have shown that daily treatment with the antibiotic isoniazid (INH) significantly reduces TB disease risk in persons known to be co-infected with HIV and TB.

The tuberculin skin test, which involves injecting TB-derived proteins below the skin, is the only method available for diagnosing inactive, or latent, TB infection. Palpable swelling at the site of injection occurs in most TB-infected people with healthy immune systems. However, HIV-infected people with suppressed immune systems often exhibit anergy, a reduced or absent reaction to skin tests for TB as well as other infections. In such persons, TB infection can be masked by a false negative skin test. As a precaution against activation of a possible latent TB infection, in 1991 the Centers for Disease Control and Prevention (CDC) suggested that INH preventive therapy be given to anergic HIV-infected individuals at high risk for TB. High-risk individuals include those who belong to groups, such as homeless persons and those who inject drugs, in which the prevalence of TB infection is at least 10 percent.

To determine the effectiveness of INH prophylaxis in this population, investigators in NIAID's Terry Beirn Community Programs for Clinical Research on AIDS (CPCRA) divided more than 500 high-risk HIV-infected people with anergy into groups that received either daily INH or placebo. They found that the number of cases of active TB disease that developed in each group during the six-month study period did not differ significantly.

"Our findings suggest that giving INH to people in this group is probably not warranted," says lead author Fred M. Gordin, M.D., of the Veterans Affairs Medical Center in Washington, D.C. "It would be more appropriate to reserve INH preventive therapy for HIV-infected persons who have a prior history of a positive TB skin test or who have been in recent contact with someone with active TB disease."

In fact, revised guidelines for preventing TB and other opportunistic infections in HIV-infected individuals, developed by the U.S. Public Health Service (PHS) and the Infectious Diseases Society of America, (IDSA) recommend just that: daily INH for persons with positive TB skin tests and for those in close contact with someone known to have active TB. The PHS/IDSA Working Group considered the findings of Dr. Gordin and his colleagues in developing the guidelines, which were published in the June 27, 1997 issue of Morbidity and Mortality Weekly Report.

"The low rates of TB in both the treatment and placebo groups (three cases out of 260 patients, and six cases out of 257 patients, respectively)," says Dr. Gordin, "indicate that TB may be under much better control than in 1991 when the CDC suggested that INH preventive therapy might be useful in anergic patients."

Dr. Gordin adds that in addition to saving the considerable programmatic costs associated with administering prophylactic INH to anergic HIV-infected individuals, a more selective use of INH would allow many people to avoid the known toxic side effects of INH. For example, about 2 percent of persons who take INH develop hepatitis.

The CPCRA is a network of primary care physicians and nurses who work with NIAID staff to design and conduct community-based clinical trials in patients with HIV disease and AIDS. NIAID currently funds 15 CPCRA units in 14 cities throughout the United States.

NIAID is a component of the National Institutes of Health (NIH). NIAID conducts and supports research to prevent, diagnose and treat illnesses such as AIDS and other sexually transmitted diseases, tuberculosis, asthma and allergies. NIH is an agency of the U.S. Department of Health and Human Services.

NIAID press releases, fact sheets and other materials are available on the Internet via the NIAID home page at http://www.niaid.nih.gov.