Dick Menzies and colleagues report findings from a collaborative, individual patient-level meta-analysis of treatment outcomes among patients with multidrug-resistant tuberculosis.

Transient worsening of tuberculous symptomatology and lesions following antituberculous therapy (paradoxical response) has previously been described as a rare occurrence. To determine the incidence of paradoxical responses in patients with AIDS and TB who are treated with antituberculous therapy and subsequently with combination antiretroviral therapy (ARV), we conducted a prospective study of 33 HIV-seropositive TB patients treated with anti-TB therapy and antiretroviral therapy (Group 1) compared with 55 HIV-seronegative TB patients treated with anti-TB therapy (Group 2) and 28 HIV-seropositive TB patients treated with anti-TB therapy but not on antiretrovirals (historical control; Group 3). In Group 1 patients, paradoxical responses were temporally more related to the initiation of ARV than to the initiation of anti-TB therapy (mean +/- SD: 15 +/- 11 d versus 109 +/- 72 d [p < 0.001]) and occurred much more frequently (12 of 33; 36%) compared with Group 2 (1 of 55; 2%) (p < 0.001) or with Group 3 (2 of 28; 7%) (p = 0.013). The majority of patients who experienced paradoxical responses and received tuberculin purified protein derivative (PPD) in Group 1 had their tuberculin skin tests convert from negative to strongly positive after ARV. These observations suggest that a paradoxical response associated with enhanced tuberculin skin reactivity may occur after the initiation of ARV in HIV-infected TB patients. Furthermore, the skin test conversion after the initiation of ARV may have important public health implications.

DST for ethambutol, pyrazinamide, and second-line tuberculosis drugs appears to provide clinically useful information to guide selection of treatment regimens for MDR and XDR tuberculosis.

The increased risk of developing lung diseases in cigarette smokers has been well recognized. The association between smoking and the risk of developing pulmonary infections in HIV-1-infected patients, however, which has not been established, was evaluated in the present study. Twenty-seven cases with lower respiratory infections (15 Pneumocystis carinii pneumonia (PCP), 12 TB cases) were compared with 27 age, gender, socio-economic and HIV status-matched patients, without history of respiratory diseases. Medical history and physical examinations were obtained every 6 months. Blood was drawn for CD4 and viral load measurements. A substantial number of HIV + smokers who developed PCP (one-third) had been on highly active retroviral therapy (HAART) for more than 6 months and prophylaxis had been discontinued. Multivariate analyses indicated that in HIV-infected people, after controlling for HIV status and antiretrovirals, cigarette smoking doubled the risk for developing PCP (p = 0.01). Multivariate analyses demonstrated that long-term smoking also increased the risk (2 x) of developing tuberculosis (p = 0.04). Moreover, daily tobacco use seemed to attenuate by 40% the immune and virological response to antiretroviral therapies. These findings indicate that tobacco use significantly increases the risk of pulmonary diseases in HIV infected subjects and has a potential deleterious impact on antiretroviral treatment.

Pyrazinamide concentrations and most pharmacokinetic parameters were comparable to those previously published. Apparent half-life was somewhat shorter than that in previous reports. Compared with adults, absorption of pyrazinamide in children appeared more likely to be incomplete or delayed.