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. 4 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 0.20x10(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.