Lack of efficacy of isoniazid chemoprophylaxis in the preventions of tuberculosis in hiv - 1 infected adults

Abstract

Background: Six months of daily isoniazid has been shown to be effective in preventing tuberculosis in the pre-HIV era. Because of underlying immune dysfunction and increased susceptibility to new infection this efficacy cannot be assumed in HIV -infected individuals.

Methods.

In a double-blind, placebo controlled clinical trial, 684 HIV -1 infected adults received either

isoniazid 300 mg daily for six months or placebo and were followed for a median of 1.8 years. The major outcomes of interest were the incidence of tuberculosis and mortality in the two

groups. .

Results.

Three hundred and forty-two subjects received isoniazid and 342 received placebo. The median

CD4lymphocyte count was 322 and 346 per cubic millimetre in the isoniazid and placebo groups

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respectively. The total period of follow-up of subjects was 583 person-years of observation

(PYO) in the isoniazid group and 595 PYO in the placebo group. The incidence of tuberculosis in the isoniazid group was 4.29 per 100 PYO (95% CI 2.78-6.33) and 3.86 per 100PYO (95% CI 2.45-5.79) in the placebo group, which allowing for confounders gave an adjusted rate ratio for isoniazid versus placebo of 0.82 (95% CI 0.39-1.73). The adjusted rate ratio for isoniazid versus placebo for tuberculin skin test positive subjects was 0.54 (95% CI 0.17-1.74) and for the tuberculin skin test negative subjects, 1.10 (95% CI 0.42-2.91). The adjusted mortality rate ratio for isoniazid versus placebo for tuberculin skin test positive subjects was 0.21 (95% Cl 0.04- 1.06) and for tuberculin skin test negative subjects, 1.08 (95% CI 0.63-1.87).