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.

The natural history, current status, and future trends of HIV infection.

Nearly 50 million people worldwide have been infected with human immunodeficiency virus (HIV), and an estimated 12 to 13 million children have been orphaned by the acquired immune deficiency syndrome (AIDS) epidemic. The natural history of HIV infection continues to evolve as researchers and clinicians unearth new facts about the virus and develop new treatment regimens for patients. The status of anti-HIV treatments is never static but constantly changing. Patients and providers struggle with adherence issues. Vaccine development, viewed as an essential step in controlling the epidemic, is complicated by the genetic diversity of the virus and the inability of the body to clear the virus. Tremendous strides have occurred in the HIV/AIDS arena, yet daunting challenges remain. This overview article presents the natural history, the current status, and future trends of HIV infection.

Relapse rates after short-course (6-month) treatment of tuberculosis in HIV-infected and uninfected persons.

OBJECTIVE: To determine the rate of tuberculosis relapse among HIV-seropositive and -seronegative persons treated for active tuberculosis with short-course (6-month) therapy. DESIGN: Consecutive cohort study. SETTING: City of Baltimore tuberculosis clinic. PATIENTS: Tuberculosis patients treated between 1 January 1993 and 31 December 1996. INTERVENTION: Patients received 2 months of isoniazid, rifampin, pyrazinamide and ethambutol followed by 4 months of isoniazid and rifampin. MAIN OUTCOME MEASURE: Passive follow-up for tuberculosis relapse was performed through September 30, 1998. RESULTS: There were 423 cases of tuberculosis during the study period; 280 patients completed a 6-month course of therapy. Therapy was directly-observed for 94% of patients. Of those who completed therapy, 47 (17%) were HIV-seropositive, 127 (45%) were HIV-seronegative, and 106 (38%) had unknown HIV status. HIV-infected patients required more time to complete therapy (median 225 versus 205 days; P = 0.04) but converted sputum culture to negative within the same time period (median 77 versus 72 days; P = 0.43) as HIV-seronegative or unknown patients. Relapse occurred in three out of 47 (6.4%) HIV-infected patients compared to seven out of 127 (5.5%) HIV-seronegative patients (P = 1.0). Relapse rates also did not differ when HIV-seropositive patients were compared with HIV-seronegative and patients with unknown HIV status (6.4% versus 3.0%; P = 0.38). Of the 10 patients with tuberculosis relapse, restriction fragment length polymorphism data were available for five; all five relapse isolates matched the initial isolate. CONCLUSIONS: These results support current recommendations to treat tuberculosis in HIV-infected patients with short-course (6-month) therapy.

Effectiveness of supervised, intermittent therapy for tuberculosis in HIV-infected patients.

OBJECTIVE: To evaluate the effectiveness of supervised therapy for tuberculosis (TB) in patients with HIV infection. DESIGN: Retrospective, chart review. PATIENTS: Patients with TB and HIV infection. SETTING: Urban, public TB clinic. MAIN MEASURES AND RESULTS: A total of 107 patients with TB and HIV infection were studied. Most were men (78%), African American (91%), uninsured or on Medicaid (88%), and 67% were injecting drug users. TB was diagnosed before AIDS in 31% of subjects, at the time of AIDS in 32%, and after AIDS in 37%. Clinical features varied by stage of HIV disease. Sixteen patients received no therapy and died before TB was diagnosed, 10 died during the first 8 weeks of treatment. Seventy-eight patients received > 8 weeks therapy, of whom 48 (62%) were given directly observed therapy twice weekly and 30 (38%) received self-administered daily therapy. Patients who received directly observed therapy were more likely to complete 6 months of therapy (96 versus 76%, P = 0.02) and more likely to survive after therapy ended (85 versus 57%, P = 0.01). By logistic regression, directly observed therapy, AIDS diagnosed before TB, and age were significantly associated with survival outcome. CONCLUSION: Directly observed therapy for TB in patients with HIV infection is highly effective and associated with better adherence to therapy and survival.