Effect of isoniazid chemoprophylaxis on HIV-related mycobacterial disease

Objectives: The aims of this study were to (1) identify trends and risk factors for mycobacterial disease and (2) determine the effect of expanded access to isoniazid chemoprophylaxis on tuberculosis incidence. Methods: A prospective observational cohort study was conducted among community-based injecting drug users (IDUs); 2960 IDUs (942 human immunodeficiency virus [HIV] seropositive) were followed up from January 1988 to June 1994. Directly obsenied chemoprophylaxis with twice-weekly isoniazid (10 to 15 mg/kg) was offered to purified protein derivative (PPD) tuberculin-positive (greater than or equal to 5-mm induration diameter in HIV-seropositive subjects and greater than or equal to 10-mm diameter in HIV-seronegative subjects) individuals but not to those with cutaneous anergy. Overall and annual incidence rates of disease due Mycobacterium tuberculosis, Mycobncterium avium complex, and other atypical mycobacteria were estimated using Poisson regression. Results: HIV seropositivity was the strongest risk factor for tuberculosis, M avizlm complex, and other mycobacterial disease (relative risk [RR], 3.8, 17.2, and 6.9, respectively). Median CD4 lymphoc>rte cell counts for the three groups of mycobacterial disease were 0.17, 0.03, and 0.02 x 10(9)/L(167/mu L, 30/mu L, and 18/mu L) within 6 months of diagnosis (before or after). Overall incidence rates of tuberculosis, M avilcm complex disease, and other mycobacterial disease were 1.9, 8.8, and 2.7 per 1000 person-years, respectively. Tuberculosis incidence peaked in 1991 at six per 1000 person-years. However, after access to directly observed preventive therapy was expanded for tuberculin-positive subjects, incidence fell to only one case in 1992 and zero cases for 24 months from mid-1992 to mid-1994. During this period the number of PPD-positiTie patients who completed at least 26 weeks of therapy (or were still receiving isoniazid) more than tripled (from 21 to 70). None of the 12 patients with tuberculosis diagnosed during follow-up had received any preventive therapy. In addition, no tuberculosis developed among participants with cutaneous anergy. Calendar trends in risk for M nvizlm complex and tuberculosis diverged after expanded access to isoniazid prophylaxis. Compared with 1988-1989, risk ofM nvium complex increased sevenfold. Tuberculosis risk fell 83% from the peak risk in 1990-1991. Conclusions: Expanded access to directly observed isoniazid therapy for tuberculin-positive IDUs with and without HIV infection was associated with an 83% drop in tuberculosis incidence, while in the same period M nviuln complex incidence significantly increased. These population-based data are consistent with those obtained from clinical trials of isoniazid prophylaxis and were obtained without offering chemoprophylaxis to HIV-infected patients with cutaneous anergy.