Impact of combination antiretroviral therapy on the risk of tuberculosis among persons with HIV infection.

OBJECTIVE: To assess the association between use of different antiretroviral regimens and incidence of tuberculosis among HIV-infected individuals. DESIGN: Observational, multicenter, prospective cohort study. SETTING AND PATIENTS: Twenty-eight infectious diseases hospital units in Italy. A total of 2160 HIV-infected persons were considered for enrolment in a study on the implementation of tuberculosis preventive therapy between 1 May 1995 and 30 April 1996. The 1360 subjects who completed tuberculin screening at base-line were included in this analysis. Information on the use of antiretroviral therapies over time was collected. The median duration of follow-up was 104 weeks and 997 subjects (73.3%) completed the study. MAIN OUTCOME MEASURE: Incidence of active tuberculosis according to different types of antiretroviral therapy. RESULTS: Eighteen cases of tuberculosis were observed with an overall incidence rate of 0.79 per 100 person-years of observation [95% confidence interval (CI), 0.51-1.31]. Tuberculin positivity and low CD4+ lymphocyte count were the only base-line variables independently associated with the risk of tuberculosis. During follow-up, 637 patients took double combination antiretroviral therapy and 387 took triple combination therapy. After adjusting for base-line characteristics of enrolled individuals, the relative hazard of tuberculosis was 0.16 (95% CI, 0.03-0.74) for double combination therapy and 0.08 (95% CI, 0.01-0.88) for triple combination therapy compared with no therapy or monotherapy. CONCLUSIONS: Combination antiretroviral therapy significantly reduced the risk of tuberculosis in HIV-infected persons. In industrialized countries, the widespread use of this treatment may determine a decrease in the incidence of HIV-associated tuberculosis, possibly contributing to a reduction in the overall incidence of tuberculosis.

Effectiveness of infection control measures in controlling a nosocomial outbreak of multidrug-resistant tuberculosis among HIV patients in Italy.

SETTING: Between October 1992 and February 1994, 33 cases of multidrug-resistant tuberculosis (MDR-TB) were diagnosed among patients infected by the human immunodeficiency virus (HIV) and hospitalised in an HIV ward in Milan, Italy. This outbreak was part of a much larger outbreak, begun in another hospital and probably transferred through a patient. OBJECTIVE: To evaluate risk factors for transmission and the effectiveness of infection control measures. DESIGN: 1) Active follow-up of exposed patients, 2) cohort study among HIV-infected patients exposed to MDR-TB cases before and after the implementation of control measures, 3) screening of close contacts of MDR-TB cases, and 4) molecular typing by restriction fragment length polymorphism (RFLP) analysis. RESULTS: The risk of MDR-TB was higher in patients with lower CD4+ lymphocyte percentages and longer duration of exposure. No difference in the daily risk was observed for in-patients vs day-hospital patients or by room distance from an infectious case. Of the 90 patients exposed before the implementation of infection control measures (i.e., October 1992-June 1993) 26 (28.9%) developed MDR-TB, whereas none of the 44 patients exclusively exposed after implementation developed MDR-TB, despite the continuing presence of infectious MDR-TB cases in the ward. CONCLUSION: Simple control measures were effective in significantly reducing nosocomial transmission among patients.

An outbreak of multidrug-resistant tuberculosis involving HIV-infected patients of two hospitals in Milan, Italy. Italian Multidrug-Resistant Tuberculosis Outbreak Study Group.

OBJECTIVE: To describe an outbreak of multidrug-resistant tuberculosis (MDR-TB), amongst HIV-infected patients, spread from one hospital in Milan to another. DESIGN: Descriptive epidemiological investigation and molecular typing. METHODS: All cases identified by intensive case-finding were described in terms of clinical characteristics, previous nosocomial exposure to an infectious MDR-TB patient, previous stays in other institutional settings where exposure to MDR-TB could have occurred, and restriction fragment length polymorphism (RFLP) pattern. RESULTS: Between October 1991 and July 1995, 116 cases of MDR-TB were identified (85 at hospital A and 31 at hospital B). A single case patient, infected at hospital A, introduced the strain into hospital B. Eighty-two of the 92 strains available for fingerprinting revealed an identical pattern; 10 strains had unique RFLP patterns. Nosocomial exposure to an infectious MDR-TB patient was ascertained for 39 of the 56 patients with the 'outbreak' RFLP strain at hospital A (69.6%) and for 24 of the 26 patients at hospital B (92.3%). The median duration of exposure was 32 days at hospital A and 40 days at hospital B. For eight patients with the outbreak strain, exposure was determined to have probably occurred in other hospitals, in the community or in prison. CONCLUSIONS: This is the largest nosocomial outbreak of MDR-TB reported in Europe. Exposure to MDR-TB cases in other institutions caring for HIV-infected patients probably contributed to the spread of this epidemic. Strict control measures should be immediately adopted in order to prevent the spread of TB amongst HIV-infected patients in institutional settings in Europe.