Paradoxical worsening of tuberculosis in HIV-infected persons

Objective: To determine the incidence of paradoxical worsening of tuberculosis (TB) in HIV-infected persons. Design: Observational cohort study. Setting: Public, urban TB clinic. Patients: HIV-infected persons treated for TB between January 1, 1996, and December 31, 1999, and followed through June 30, 2000, Intervention: Patients received standard anti-TB therapy. Antiretroviral therapy was provided by primary medical providers. Patients receiving antiretroviral therapy were given nucleoside reverse transcriptase inhibitors alone or highly active antiretroviral therapy (HAART; nucleoside reverse transcriptase inhibitors in combination with a protease inhibitor or a nonnucleoside reverse transcriptase inhibitor). Main outcome measure: Paradoxical worsening of TB. Results: There were 82 TB cases in 76 patients. Paradoxical worsening was identified in 6 of 82 cases (7%; 95% confidence interval, 3 to 15%), Paradoxical worsening occurred in 3 of 28 cases (11%) in patients receiving HAART and in 3 of 44 cases (7%) in patients not receiving antiretroviral therapy (p = 0.67). Cases complicated by paradoxical worsening were more likely to have both pulmonary and extrapulmonary disease at initial diagnosis than cases without paradoxical worsening (83% vs 24%; p 0.006). TB relapse occurred in 2 of 6 cases (33%) in patients with paradoxical worsening and in 4 of 76 cases (5%) in patients without paradoxical worsening (p = 0.06). Conclusions: Paradoxical worsening of TB occurred less frequently than in previous reports and was not associated with HAART. Paradoxical worsening also appeared to be associated with an increased risk of TB relapse. Further studies are warranted to better characterize the risk factors for paradoxical worsening and the appropriate duration of anti-TB therapy in patients in whom it occurs.