Treatment with Isoniazid for patients with anergy and HIV who are at high risk for Tuberculosis

Debra Bynum, M.D.

August 22, 1997

Clinical Bottom Lines:

1. There was no significant difference in the development of Tuberculosis between patients with HIV and anergy on PPD testing treated with 6 months of Isoniazid (1.15%) compared to those with HIV and anergy who received placebo (2.3%)

2. There was no significant difference in either death or the combined endpoints of death and progression of HIV disease.

3. There was no significant difference in adverse events, including hepatitis or neuropathy, between those treated with Isoniazid compared to placebo.

The Evidence:

Multicenter, double blind, placebo controlled trial with 517 patients randomized to receive 6 months of Isoniazid or placebo with a primary endpoint of culture confirmed Tuberculosis (pulmonary or extrapulmonary). Secondary endpoints included mortality and clinical progression of HIV disease.

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  Isoniazid (N=260) Placebo (N=257) Relative Risk P value
Tuberculosis 3 (1.15%) 6 (2.3%) 0.48 (.12-1.91) 0.30
Death 129 (49.6%) 126 (49.0%) 0.96 (0.75-1.23) 0.76
Progression of HIV or death 155 (59.6%) 154 (59.9%) 0.97 (0.77-1.21) 0.78

Comments:

1. The trial was well designed and included patients considered at high risk for TB (over 90% of the patients had 2 or more risk factors for the development of TB including birth outside of the US, drug or alcohol use, unemployment, homelessness, and distant close contact with someone who had active TB.

2. The small numbers and low rate of TB limit the power of the study

3. An average follow-up of 34 months may not be adequate when dealing with TB!

4. There was no significant difference in adverse events between the two groups, but the trial excluded patients with any evidence of active hepatitis or neuropathy (which is not uncommon in patients with HIV and risk factors for TB)

5. The trial also excluded patients with HIV and anergy who had had recent contact with someone with active tuberculosis -- therefore this data cannot be used to justify not giving INH in this situation.

Reference: Gordin FM et al. A Controlled Trial of Isoniazid in Persons with Anergy and HIV Infection Who Are at High Risk for Tubercolosis. N Engl J Med 1997; 337:315-20.