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dc.contributor.authorBoulware, David R.
dc.contributor.authorMeya, David B.
dc.contributor.authorMuzoora, Conrad
dc.contributor.authorRolfes, Melissa A.
dc.contributor.authorHullsiek, Katherine Huppler
dc.contributor.authorMusubire, Abdu
dc.contributor.authorTaseera, Kabanda
dc.contributor.authorNabeta, Henry W.
dc.contributor.authorSchutz, Charlotte
dc.contributor.authorWilliams, Darlisha A
dc.contributor.authorRajasingham, Radha
dc.contributor.authorRhein, Joshua
dc.contributor.authorThienemann, Friedrich
dc.contributor.authorLo, Melanie W
dc.contributor.authorNielsen, Kirsten
dc.contributor.authorBergemann, Tracy L.
dc.contributor.authorKambugu, Andrew
dc.contributor.authorManabe, Yukari C.
dc.contributor.authorJanoff, Edward N.
dc.contributor.authorBohjanen, Paul R.
dc.contributor.authorMeintjes, Graeme
dc.date.accessioned2015-05-07T06:30:55Z
dc.date.available2015-05-07T06:30:55Z
dc.date.issued2014
dc.identifier.citationBoulware, D. R. (2014). Timing of antiretroviral therapy after diagnosis of cryptococcal meningitisen_US
dc.identifier.otherDOI: 10.1056/NEJMoa1312884
dc.identifier.urihttp://hdl.handle.net/10570/4404
dc.description.abstractBackground 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.description.sponsorshipSupported by grants from the National Institute of Allergy and Infectious Diseases (NIAID; U01AI089244, K23AI073192, T32AI055433, and K24AI096925), the Wellcome Trust (081667 and 098316 and the Veterans Affairs Research Serviceen_US
dc.language.isoenen_US
dc.publisherMassachusetts Medical Societyen_US
dc.subjectAntiretroviral Therapyen_US
dc.subjectCryptococcal Meningitisen_US
dc.titleTiming of Antiretroviral Therapy after Diagnosis of Cryptococcal Meningitisen_US
dc.typeJournal articleen_US


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