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Timing of Antiretroviral Therapy after Diagnosis of Cryptococcal Meningitis

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dc.contributor.author Boulware, David R.
dc.contributor.author Meya, David B.
dc.contributor.author Conrad, Muzoora
dc.contributor.author Rolfes, Melissa A.
dc.contributor.author Hullsiek, Katherine Huppler
dc.contributor.author Musubire, Abdu
dc.contributor.author Taseera M., Kabanda
dc.contributor.author Nabeta, Henry W.
dc.contributor.author Schutz, Charlotte
dc.contributor.author Williams, Darlisha A.
dc.contributor.author Rajasingham, Radha
dc.contributor.author Rhein, Joshua
dc.contributor.author Thienemann, Friedrich
dc.contributor.author Lo, Melanie W.
dc.contributor.author Nielsen, Kirsten
dc.contributor.author Bergemann, Tracy L.
dc.contributor.author Kambugu, Andrew
dc.contributor.author Munabe, Yukari C.
dc.contributor.author Janoff, Edward N.
dc.contributor.author Bohjanen, Paul R.
dc.contributor.author Meintjes, Graeme
dc.date.accessioned 2014-08-06T05:50:34Z
dc.date.available 2014-08-06T05:50:34Z
dc.date.issued 2014
dc.identifier.citation Boulware d r ET AL (2014). Timing of Antiretroviral Therapy after Diagnosis of Cryptococcal Meningitis. The New England Journal of Medicine, 370 (26): 2487-2498. en_US
dc.identifier.other DOI: 10.1056/NEJMoa1312884
dc.identifier.uri http://hdl.handle.net/10570/3483
dc.description.abstract Background Cryptococcal meningitis accounts for 20 to 25% of acquired immunodeficiency syndrome–related deaths in Africa. Antiretroviral therapy (ART) is essential for survival; however, the question of when ART should be initiated after diagnosis of cryptococcal meningitis remains unanswered. Methods We assessed survival at 26 weeks among 177 human immunodeficiency virus–infected adults in Uganda and South Africa who had cryptococcal meningitis and had not previously received ART. We randomly assigned study participants to undergo either earlier ART initiation (1 to 2 weeks after diagnosis) or deferred ART initiation (5 weeks after diagnosis). Participants received amphotericin B (0.7 to 1.0 mg per kilogram of body weight per day) and fluconazole (800 mg per day) for 14 days, followed by consolidation therapy with fluconazole. Results The 26-week mortality with earlier ART initiation was significantly higher than with deferred ART initiation (45% [40 of 88 patients] vs. 30% [27 of 89 patients]; hazard ratio for death, 1.73; 95% confidence interval [CI], 1.06 to 2.82; P = 0.03). The excess deaths associated with earlier ART initiation occurred 2 to 5 weeks after diagnosis (P = 0.007 for the comparison between groups); mortality was similar in the two groups thereafter. Among patients with few white cells in their cerebrospinal fluid (<5 per cubic millimeter) at randomization, mortality was particularly elevated with earlier ART as compared with deferred ART (hazard ratio, 3.87; 95% CI, 1.41 to 10.58; P = 0.008). The incidence of recognized cryptococcal immune reconstitution inflammatory syndrome did not differ significantly between the earlier-ART group and the deferred-ART group (20% and 13%, respectively; P = 0.32). All other clinical, immunologic, virologic, and microbiologic outcomes, as well as adverse events, were similar between the groups. Conclusions Deferring ART for 5 weeks after the diagnosis of cryptococcal meningitis was associated with significantly improved survival, as compared with initiating ART at 1 to 2 weeks, especially among patients with a paucity of white cells in cerebrospinal fluid. (Funded by the National Institute of Allergy and Infectious Diseases and others; COAT ClinicalTrials.gov number, NCT01075152.) en_US
dc.language.iso en en_US
dc.publisher The New England Journal of Medicine en_US
dc.subject Antiretroviral Therapy en_US
dc.subject Cryptococcal Meningitis en_US
dc.subject Diagnosis en_US
dc.title Timing of Antiretroviral Therapy after Diagnosis of Cryptococcal Meningitis en_US
dc.type Article en_US


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