TY - JOUR
T1 - Timing of initiation of antiretroviral therapy in human immunodeficiency virus (HIV)--associated tuberculous meningitis
AU - Török, M. Estee
AU - Yen, Nguyen Thi Bich
AU - Chau, Tran Thi Hong
AU - Mai, Nguyen Thi Hoang
AU - Phu, Nguyen Hoan
AU - Mai, Pham Phuong
AU - Dung, Nguyen Thi
AU - Chau, Nguyen Van Vinh
AU - Bang, Nguyen Duc
AU - Tien, Nguyen Anh
AU - Minh, N. H.
AU - Hien, Nguyen Quang
AU - Thai, Phan Vuong Khac
AU - Dong, Doan The
AU - Anh, Do Thi Tuong
AU - Thoa, Nguyen Thi Cam
AU - Hai, Nguyen Ngoc
AU - Lan, Nguyen Ngoc
AU - Lan, Nguyen Thi Ngoc
AU - Quy, Hoang Thi
AU - Dung, Nguyen Huy
AU - Hien, Tran Tinh
AU - Chinh, Nguyen Tran
AU - Simmons, Cameron Paul
AU - de Jong, Menno
AU - Wolbers, Marcel
AU - Farrar, Jeremy James
PY - 2011
Y1 - 2011
N2 - The optimal time to initiate antiretroviral therapy (ART) in human immunodeficiency virus (HIV)-associated tuberculous meningitis is unknown. 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. 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). 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
AB - The optimal time to initiate antiretroviral therapy (ART) in human immunodeficiency virus (HIV)-associated tuberculous meningitis is unknown. 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. 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). 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
U2 - https://doi.org/10.1093/cid/cir230
DO - https://doi.org/10.1093/cid/cir230
M3 - Article
C2 - 21596680
SN - 1058-4838
VL - 52
SP - 1374
EP - 1383
JO - Clinical Infectious Diseases
JF - Clinical Infectious Diseases
IS - 11
ER -