title: Timing of initiation of antiretroviral therapy in human immunodeficiency virus (HIV)--associated tuberculous meningitis.
abstract: 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: Department of Infectious Diseases, Cambridge University Hospitals National Health Service Foundation Trust, Cambridge, United Kingdom. estee.torok@addenbrookes.nhs.uk
authors: M Estee
authors: ME
authors: Török
authors: Nguyen Thi Bich
authors: NT
authors: Yen
authors: Tran Thi Hong
authors: TT
authors: Chau
authors: Nguyen Thi Hoang
authors: NT
authors: Mai
authors: Nguyen Hoan
authors: NH
authors: Phu
authors: Pham Phuong
authors: PP
authors: Mai
authors: Nguyen Thi
authors: NT
authors: Dung
authors: Nguyen Van Vinh
authors: NV
authors: Chau
authors: Nguyen Duc
authors: ND
authors: Bang
authors: Nguyen Anh
authors: NA
authors: Tien
authors: N H
authors: NH
authors: Minh
authors: Nguyen Quang
authors: NQ
authors: Hien
authors: Phan Vuong Khac
authors: PV
authors: Thai
authors: Doan The
authors: DT
authors: Dong
authors: Do Thi Tuong
authors: DT
authors: Anh
authors: Nguyen Thi Cam
authors: NT
authors: Thoa
authors: Nguyen Ngoc
authors: NN
authors: Hai
authors: Nguyen Ngoc
authors: NN
authors: Lan
authors: Nguyen Thi Ngoc
authors: NT
authors: Lan
authors: Hoang Thi
authors: HT
authors: Quy
authors: Nguyen Huy
authors: NH
authors: Dung
authors: Tran Tinh
authors: TT
authors: Hien
authors: Nguyen Tran
authors: NT
authors: Chinh
authors: Cameron Paul
authors: CP
authors: Simmons
authors: Menno
authors: M
authors: de Jong
authors: Marcel
authors: M
authors: Wolbers
authors: Jeremy James
authors: JJ
authors: Farrar
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