Timing of initiation of antiretroviral therapy in human immunodeficiency virus (HIV)–associated tuberculous meningitis
<p><b>Background:</b> The optimal time to initiate antiretroviral therapy (ART) in human immunodeficiency virus (HIV)–associated tuberculous meningitis is unknown.<br/> <b>Methods:</b> We conducted a randomized, double-blind, placebo-controlled trial of immediate...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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Oxford University Press
2011
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| _version_ | 1826294206343151616 |
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| author | Török, M Yen, N Chau, T Mai, N Phu, N Mai, P Dung, N Chau, N Bang, N Tien, N Minh, N Hien, N Thai, P Dong, D Anh, D Thoa, N Hai, N Lan, N Lan, N Quy, H Dung, N Hien, T Chinh, N Simmons, C De Jong, M Wolbers, M Farrar, J |
| author_facet | Török, M Yen, N Chau, T Mai, N Phu, N Mai, P Dung, N Chau, N Bang, N Tien, N Minh, N Hien, N Thai, P Dong, D Anh, D Thoa, N Hai, N Lan, N Lan, N Quy, H Dung, N Hien, T Chinh, N Simmons, C De Jong, M Wolbers, M Farrar, J |
| author_sort | Török, M |
| collection | OXFORD |
| description | <p><b>Background:</b> The optimal time to initiate antiretroviral therapy (ART) in human immunodeficiency virus (HIV)–associated tuberculous meningitis is unknown.<br/> <b>Methods:</b> 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.<br/> <b>Results:</b> 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).<br/> <b>Conclusions:</b>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.<br/> <b>Clinical Trials Registration:</b> ISRCTN63659091.</p> |
| first_indexed | 2024-03-07T03:42:03Z |
| format | Journal article |
| id | oxford-uuid:be3d5bd1-3e44-4a19-bfc3-c9bf5a311237 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T03:42:03Z |
| publishDate | 2011 |
| publisher | Oxford University Press |
| record_format | dspace |
| spelling | oxford-uuid:be3d5bd1-3e44-4a19-bfc3-c9bf5a3112372022-03-27T05:37:50ZTiming of initiation of antiretroviral therapy in human immunodeficiency virus (HIV)–associated tuberculous meningitisJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:be3d5bd1-3e44-4a19-bfc3-c9bf5a311237EnglishSymplectic Elements at OxfordOxford University Press2011Török, MYen, NChau, TMai, NPhu, NMai, PDung, NChau, NBang, NTien, NMinh, NHien, NThai, PDong, DAnh, DThoa, NHai, NLan, NLan, NQuy, HDung, NHien, TChinh, NSimmons, CDe Jong, MWolbers, MFarrar, J<p><b>Background:</b> The optimal time to initiate antiretroviral therapy (ART) in human immunodeficiency virus (HIV)–associated tuberculous meningitis is unknown.<br/> <b>Methods:</b> 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.<br/> <b>Results:</b> 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).<br/> <b>Conclusions:</b>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.<br/> <b>Clinical Trials Registration:</b> ISRCTN63659091.</p> |
| spellingShingle | Török, M Yen, N Chau, T Mai, N Phu, N Mai, P Dung, N Chau, N Bang, N Tien, N Minh, N Hien, N Thai, P Dong, D Anh, D Thoa, N Hai, N Lan, N Lan, N Quy, H Dung, N Hien, T Chinh, N Simmons, C De Jong, M Wolbers, M Farrar, J 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 |
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