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

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 tuberc...

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Autore principale: Simmons, Cameron
Natura: Journal Article
Lingua:inglese
Pubblicazione: 2018
Accesso online:https://demo7.dspace.org/handle/123456789/147
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author Simmons, Cameron
author_browse Simmons, Cameron
author_facet Simmons, Cameron
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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.
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spelling oai:localhost:123456789-1472021-04-07T16:30:08Z Timing of Initiation of Antiretroviral Therapy in Human Immunodeficiency Virus (HIV)-Associated Tuberculous Meningitis Simmons, Cameron 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. 2018-09-14T11:14:59Z 2017-07-12T04:47:43Z 2018-09-14T11:14:59Z 2011-06-01 Journal Article https://demo7.dspace.org/handle/123456789/147 English
spellingShingle Simmons, Cameron
Timing of Initiation of Antiretroviral Therapy in Human Immunodeficiency Virus (HIV)-Associated Tuberculous Meningitis
title Timing of Initiation of Antiretroviral Therapy in Human Immunodeficiency Virus (HIV)-Associated Tuberculous Meningitis
title_full Timing of Initiation of Antiretroviral Therapy in Human Immunodeficiency Virus (HIV)-Associated Tuberculous Meningitis
title_fullStr Timing of Initiation of Antiretroviral Therapy in Human Immunodeficiency Virus (HIV)-Associated Tuberculous Meningitis
title_full_unstemmed Timing of Initiation of Antiretroviral Therapy in Human Immunodeficiency Virus (HIV)-Associated Tuberculous Meningitis
title_short Timing of Initiation of Antiretroviral Therapy in Human Immunodeficiency Virus (HIV)-Associated Tuberculous Meningitis
title_sort timing of initiation of antiretroviral therapy in human immunodeficiency virus hiv associated tuberculous meningitis
url https://demo7.dspace.org/handle/123456789/147
work_keys_str_mv AT simmonscameron timingofinitiationofantiretroviraltherapyinhumanimmunodeficiencyvirushivassociatedtuberculousmeningitis