| Title: |
Timing of initiation of antiretroviral therapy in human immunodeficiency virus (HIV)-associated tuberculous meningitis |
| Authors: |
Török, ME; Yen, NTB; Chau, TTH; Mai, NTH; Phu, NH; Mai, PP; Dung, NT; Chau, NVV; Bang, ND; Tien, NA; Minh, NH; Hien, NQ; Thai, PVK; Dong, DT; Anh, DTT; Thoa, NTC; Hai, NN; Lan, NN; Lan, NTN; Quy, HT; Dung, NH; Hien, TT; Chinh, NT; Simmons, CP; De Jong, M; Wolbers, M; Farrar, JJ |
| Publisher Information: |
OXFORD UNIV PRESS INC |
| Publication Year: |
2011 |
| Collection: |
The University of Melbourne: Digital Repository |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| ISSN: |
1058-4838 |
| Relation: |
pii: cir230; https://hdl.handle.net/11343/191110 |
| Availability: |
https://hdl.handle.net/11343/191110 |
| Accession Number: |
edsbas.45812B85 |
| Database: |
BASE |