Timing of initiation of antiretroviral therapy in human immunodeficiency virus (HIV)--associated tuberculous meningitis.

Journal article

BACKGROUND: The optimal time to initiate antiretroviral therapy (ART) in human immunodeficiency virus (HIV)-associated tuberculous meningitis is unknown. METHODS: We conducted a randomized, double-blind, placebo-controlled trial of immediate versus deferred ART in patients with HIV-associated tuberculous meningitis to determine whether immediate ART reduced the risk of death. Antiretroviral drugs (zidovudine, lamivudine, and efavirenz) were started either at study entry or 2 months after randomization. All patients were treated with standard antituberculosis treatment, adjunctive dexamethasone, and prophylactic co-trimoxazole and were followed up for 12 months. We conducted intention-to-treat, per-protocol, and prespecified subgroup analyses. RESULTS: A total of 253 patients were randomized, 127 in the immediate ART group and 126 in the deferred ART group; 76 and 70 patients died within 9 months in the immediate and deferred ART groups, respectively. Immediate ART was not significantly associated with 9-month mortality (hazard ratio [HR], 1.12; 95% confidence interval [CI], .81-1.55; P = .50) or the time to new AIDS events or death (HR, 1.16; 95% CI, .87-1.55; P = .31). The percentage of patients with severe (grade 3 or 4) adverse events was high in both arms (90% in the immediate ART group and 89% in the deferred ART group; P = .84), but there were significantly more grade 4 adverse events in the immediate ART arm (102 in the immediate ART group vs 87 in the deferred ART group; P = .04). CONCLUSIONS: Immediate ART initiation does not improve outcome in patients presenting with HIV-associated tuberculous meningitis. There were significantly more grade 4 adverse events in the immediate ART arm, supporting delayed initiation of ART in HIV-associated tuberculous meningitis. Clinical Trials Registration. ISRCTN63659091.

Authors: Török, M; Yen, N; Chau, T; Mai, N; Phu, N

• Publication status: Published
• Journal: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
• Volume: 52
• Issue: 11
• Pages: 1374-1383
• Publication date: 2011-06-01
• DOI: 10.1093/cid/cir230
• EISSN: 1537-6591
• ISSN: 1058-4838
• Language: English
• Keywords: Dexamethasone; Double-Blind Method; Time Factors; Anti-HIV Agents; HIV Infections; Lamivudine; Benzoxazines; Antitubercular Agents; Treatment Outcome; Male; Anti-Inflammatory Agents; Humans; Female; Adult; Zidovudine; Trimethoprim-Sulfamethoxazole Combination; Antiretroviral Therapy, Highly Active; Tuberculosis, Meningeal; Placebos