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

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

Research output: Contribution to journalArticleResearchpeer-review

228 Citations (Scopus)

Abstract

(See the editorial commentary Lawn and Wood, on pages 1384-1387.) 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). Conclusion s.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.

Original languageEnglish
Pages (from-to)1374-1383
Number of pages10
JournalClinical Infectious Diseases
Volume52
Issue number11
DOIs
Publication statusPublished - 1 Jun 2011
Externally publishedYes

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