Journal Article

Timing of Initiation of Antiretroviral Therapy in Human Immunodeficiency Virus (HIV)—Associated Tuberculous Meningitis

Hien, Tran Tinh, Mai, Nguyen Thi Hoang, Lan, Nguyen Ngoc, Farrar, Jeremy James, Török, M. Estee, Tien, Nguyen Anh, Anh, Do Thi Tuong, Dung, Nguyen Huy, Chinh, Nguyen Tran, Simmons, Cameron Paul, Bang, Nguyen Duc, Chau, Tran Thi Hong, Thoa, Nguyen Thi Cam, Yen, Nguyen Thi Bich, Minh, N. H., Jong, Menno de, Wolbers, Marcel, Dong, Doan The, Thai, Phan Vuong Khac, Van Vinh Chau, Nguyen, Quy, Hoang Thi, Phu, Nguyen Hoan, Mai, Pham Phuong, Lan, Nguyen Thi Ngoc, Hien, Nguyen Quang, Dung, Nguyen Thi, Hai, Nguyen Ngoc

2011

Overview

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, perprotocol, 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.

• Publisher: Oxford University Press
• Subject: Adult / AIDS / Alkynes / Anti-HIV Agents - administration & dosage / Anti-HIV Agents - adverse effects / Anti-Inflammatory Agents - administration & dosage / Antibiotics. Antiinfectious agents. Antiparasitic agents / Antiretroviral agents / Antiretroviral drugs / Antiretroviral Therapy, Highly Active - adverse effects / Antiretroviral Therapy, Highly Active - methods / Antiretrovirals / Antitubercular Agents - administration & dosage / Antiviral agents / Art therapy / Arts / Bacterial diseases / Bacterial diseases of the nervous system. Bacterial myositis / Benzoxazines - administration & dosage / Biological and medical sciences / Clinical trials / Cyclopropanes / Dexamethasone - administration & dosage / Double-Blind Method / Female / HIV / HIV 1 / HIV Infections - complications / HIV Infections - drug therapy / HIV Infections - mortality / HIV/AIDS / Human bacterial diseases / Human immunodeficiency virus / Human viral diseases / Humans / Infectious diseases / Lamivudine - administration & dosage / Male / Medical sciences / Medical treatment / Meningeal tuberculosis / Meningitis / Mortality / Pharmacology. Drug treatments / Placebos - administration & dosage / Random allocation / Risk assessment / Risk reduction / Statistical median / Time Factors / Treatment Outcome / Trimethoprim, Sulfamethoxazole Drug Combination - administration & dosage / Tuberculosis, Meningeal - complications / Tuberculosis, Meningeal - drug therapy / Tuberculosis, Meningeal - mortality / Viral diseases / Viral diseases of the lymphoid tissue and the blood. Aids / Zidovudine - administration & dosage