Isoniazid preventive therapy in human immunodeficiency virus-infected persons. Long-term effect on development of tuberculosis and survival.

BACKGROUND

Although the short-term benefit of isoniazid prophylaxis in patients coinfected with human immunodeficiency virus (HIV) and tuberculosis has been shown, long-term benefits are unknown.

METHODS

Historical cohort study in an acquired immunodeficiency syndrome unit at a tertiary referral hospital. A sample of 121 HIV-infected patients with positive results on a purified protein derivative test were followed up for development of active tuberculosis and survival. Patients who received isoniazid prophylaxis were compared with patients who did not receive prophylaxis.

RESULTS

Of the 121 patients examined, 29 (24%) completed a 9- to 12-month course of isoniazid prophylaxis (median follow-up, 89 months), and 92 (76%) did not receive the drug (median follow-up, 60 months). Active tuberculosis developed in 46 patients (38%). The incidence of tuberculosis was higher among patients with no prophylaxis (9.4 per 100 patient-years) than among patients with isoniazid prophylaxis (1.6 per 100 patient-years) (P = .006). Risk for development of tuberculosis was associated with the absence of isoniazid prophylaxis (relative risk [RR], 6.55; 95% confidence interval [CI], 2.02-21.19). Death during the period of study was more frequent in patients who did not receive isoniazid (50/92 or 54%) than in patients who received isoniazid (7/29 or 24%) (P = .008). Median survival was more than 111 months in patients who received isoniazid compared with 75 months in patients who did not receive isoniazid (P < .001). In a proportional hazards analysis, the development of tuberculosis (RR, 1.88; 95% CI, 1.09-3.27), the absence of isoniazid prophylaxis (RR, 2.68; 95% CI, 1.16-6.17), and a CD4+ cell count lower than 0.20 x 10(9)/L (RR, 3.03; 95% CI, 1.39-6.61) were independently associated with death. Patients who received isoniazid had a longer survival after stratifying for the CD4+ cell count.

CONCLUSIONS

Preventive therapy with isoniazid confers long-term protection against tuberculosis and significantly increases survival in patients dually infected with HIV and Mycobacterium tuberculosis.