PARADOXICAL WORSENING OF TUBERCULOSIS FOLLOWING ANTIRETROVIRAL THERAPY IN PATIENTS WITH AIDS

Transient worsening of tuberculous symptomatology and lesions followin g antituberculous therapy (paradoxical response) has previously been d escribed as a rare occurrence. To determine the incidence of paradoxic al responses in patients with AIDS and TB who are treated with antitub erculous therapy and subsequently with combination antiretroviral ther apy (ARV), we conducted a prospective study of 33 HIV-seropositive TB patients treated with anti-TB therapy and antiretroviral therapy (Grou p 1) compared with 55 HIV-seronegative TB patients treated with anti-T B therapy (Group 2) and 28 HIV-seropositive TB patients treated with a nti-TB therapy but not on antiretrovirals (historical control; Group 3 ). In Group 1 patients, paradoxical responses were temporally more rel ated to the initiation of ARV than to the initiation of anti-TB therap y (mean +/- SD: 15 +/- 11 d versus 109 +/- 72 d [p < 0.001]) and occur red much more frequently (12 of 33; 36%) compared with Group 2 (1 of 5 5; 2%) (p < 0.001) or with Group 3 (2 of 28; 7%) (p = 0.013). The majo rity of patients who experienced paradoxical responses and received tu berculin purified protein derivative (PPD) in Group 1 had their tuberc ulin 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 conversio n after the initiation of ARV may have important public health implica tions.