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type=\u0022text\/css\u0022 rel=\u0022stylesheet\u0022 href=\u0022\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/cdn\/css\/http\/css_Xg7z6oCTVgud_Q0huYz9x9iiD5H_2YPSJ5z2ZViSWdY.css\u0022 media=\u0022all\u0022 \/\u003E\n\u003Clink rel=\u0027stylesheet\u0027 type=\u0027text\/css\u0027 href=\u0027\/sites\/all\/modules\/contrib\/panels\/plugins\/layouts\/onecol\/onecol.css\u0027 \/\u003E\u003C\/head\u003E\u003Cbody\u003E\u003Cdiv class=\u0022panels-ajax-tab-panel panels-ajax-tab-panel-sageoa-tab-art\u0022\u003E\u003Cdiv class=\u0022panel-display panel-1col clearfix\u0022 \u003E\n  \u003Cdiv class=\u0022panel-panel panel-col\u0022\u003E\n    \u003Cdiv\u003E\u003Cdiv class=\u0022panel-pane pane-highwire-markup\u0022 \u003E\n  \n      \n  \n  \u003Cdiv class=\u0022pane-content\u0022\u003E\n    \u003Cdiv class=\u0022highwire-markup\u0022\u003E\u003Cdiv xmlns=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022 id=\u0022content-block-markup\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cdiv class=\u0022article fulltext-view \u0022\u003E\u003Cspan class=\u0022highwire-journal-article-marker-start\u0022\u003E\u003C\/span\u003E\u003Cdiv class=\u0022section abstract\u0022 id=\u0022abstract-1\u0022\u003E\u003Ch2\u003ESummary\u003C\/h2\u003E\n            \u003Cp id=\u0022p-1\u0022\u003EThe first randomized, controlled trial to show a survival benefit of an antifungal treatment in HIV-infected patients with cryptococcal meningitis was completed this year in Vietnam [\u003Ca href=\u0022\/external-ref?link_type=ISRCTN\u0026amp;access_num=ISRCTN95123928\u0022 class=\u0022external-ref external-ref-type-isrctn\u0022\u003EISRCTN 95123928\u003C\/a\u003E].\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003EInfectious Disease Clinical Trials\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EHIV \u0026amp; AIDS\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EFungal Infections\u003C\/li\u003E\u003C\/ul\u003E\u003Cp id=\u0022p-2\u0022\u003EThe first randomized, controlled trial to show a survival benefit of an antifungal treatment in HIV-infected patients with cryptococcal meningitis was completed this year in Vietnam [\u003Ca href=\u0022\/external-ref?link_type=ISRCTN\u0026amp;access_num=ISRCTN95123928\u0022 class=\u0022external-ref external-ref-type-isrctn\u0022\u003EISRCTN 95123928\u003C\/a\u003E]. Results were presented by Jeremy N. Day, MD, Oxford University Clinical Research Unit, Wellcome Trust Major Overseas Programme Vietnam, in collaboration with colleagues from the Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam.\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003EThe study compared three induction-phase treatment strategies that are currently recommended by the Infectious Disease Society of America [Perfect JR et al. \u003Cem\u003EClin Infect Dis\u003C\/em\u003E 2010]. Although combination therapy with flucytosine is considered first-line therapy, a mortality benefit over other regimens has not been shown in a randomized, controlled trial. Also, there are distinct disadvantages to flucytosine use\u2014namely expense, toxicity, and poor availability in areas with high cryptococcal disease rates.\u003C\/p\u003E\u003Cp id=\u0022p-4\u0022\u003EDr. Day and his colleagues were interested in whether combining antifungal therapies in the induction phase of treatment would offer a survival advantage when compared with amphotericin monotherapy, the standard practice in Vietnam.\u003C\/p\u003E\u003Cp id=\u0022p-5\u0022\u003EEnrolled patients presented with a syndrome that was consistent with cryptococcal meningitis and microbiological evidence of \u003Cem\u003ECryptococcus\u003C\/em\u003E in the CSF and\/or blood. All patients were \u0026gt;14 years of age and HIV-positive. Patients with prior history of cryptococcal infection or prior antifungal treatment (\u0026gt;3 days) were excluded. Patients were randomly assigned to receive one of three possible induction treatments: amphotericin B 1 mg\/kg\/day monotherapy for 4 weeks (Arm I, the standard of care in Vietnam); amphotericin B 1 mg\/kg\/day plus flucytosine 100 mg\/kg\/day for 2 weeks (Arm II); or amphotericin B 1 mg\/kg\/day plus fluconazole 400 mg twice daily for 2 weeks (Arm III; \u003Ca id=\u0022xref-table-wrap-1-1\u0022 class=\u0022xref-table\u0022 href=\u0022#T1\u0022\u003ETable 1\u003C\/a\u003E). The coprimary endpoint was mortality at 2 and 10 weeks. Secondary endpoints included survival to 6 months and disability at 70 days and 6 months.\u003C\/p\u003E\u003Cdiv id=\u0022T1\u0022 class=\u0022table pos-float\u0022\u003E\u003Cdiv class=\u0022table-inline\u0022\u003E\u003Cdiv class=\u0022callout\u0022\u003E\u003Cspan\u003EView this table:\u003C\/span\u003E\u003Cul class=\u0022callout-links\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022\/\u0022 class=\u0022table-expand-inline\u0022 data-table-url=\u0022\/highwire\/markup\/12471\/expansion?postprocessors=highwire_figures%2Chighwire_math%2Chighwire_inline_linked_media%2Chighwire_embed\u0026amp;table-expand-inline=1\u0022 html=\u00221\u0022 fragment=\u0022#\u0022 external=\u00221\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView inline\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022\/highwire\/markup\/12471\/expansion?width=1000\u0026amp;height=500\u0026amp;iframe=true\u0026amp;postprocessors=highwire_figures%2Chighwire_math%2Chighwire_inline_linked_media\u0022 class=\u0022colorbox colorbox-load table-expand-popup\u0022 rel=\u0022gallery-fragment-tables\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView popup\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/12471\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cdiv class=\u0022table-caption\u0022\u003E\u003Cspan class=\u0022table-label\u0022\u003ETable 1.\u003C\/span\u003E \n            \u003Cp id=\u0022p-6\u0022 class=\u0022first-child\u0022\u003EStudy Design.\u003C\/p\u003E\n         \u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-8\u0022\u003EThe intent-to-treat (ITT) population comprised 298 patients, predominantly male, with a median age of 28 years. Approximately 30% had some level of impaired consciousness, reflected by a Glasgow coma score of \u0026lt;15. All patients underwent lumbar puncture, which revealed elevated CSF opening pressure (\u0026gt;18 cm\/CSF) in over two-thirds of patients and high yeast burdens (median 5.9 log 10 CFU\/mL).\u003C\/p\u003E\u003Cp id=\u0022p-9\u0022\u003ECompared with amphotericin monotherapy, the amphotericin+flucytosine combination was associated with a significantly reduced hazard of death by both Day 70 [HR, 0.61; 95% CI, 0.39 to 0.97; p=0.04] and Day 182 [HR, 0.56; 95% CI, 0.36 to 0.89; p=0.01] (\u003Ca id=\u0022xref-fig-1-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F1\u0022\u003EFigure 1\u003C\/a\u003E). Amphotericin B, combined with fluconazole, offered no survival advantage compared with amphotericin monotherapy. After adjusting for fungal burden and Glasgow coma score at study entry, the hazard of death by 6 months was also significantly higher among amphotericin-fluconazole-treated patients versus those who received amphotericin-flucytosine (adjusted HR for all-cause mortality, 1.81; 95% CI, 1.14 to 2.88; p=0.01). The death rate at 70 days was 30% for patients who were on combination therapy with flucytosine versus 44% for those who were on monotherapy. Rates of adverse events between the two combination regimens were comparable and included anemia, neutropenia, and renal impairment.\u003C\/p\u003E\u003Cdiv id=\u0022F1\u0022 class=\u0022fig pos-float  odd\u0022\u003E\u003Cdiv class=\u0022highwire-figure\u0022\u003E\u003Cdiv class=\u0022fig-inline-img-wrapper\u0022\u003E\u003Cdiv class=\u0022fig-inline-img\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/11\/12\/9\/F1.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022Kaplan-Meier Curve of Survival Outcomes Among ITT Population.\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-1894495279\u0022 data-figure-caption=\u0022Kaplan-Meier Curve of Survival Outcomes Among ITT Population.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003E\u003Cimg class=\u0022fragment-image\u0022 alt=\u0022Figure 1.\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/11\/12\/9\/F1.medium.gif\u0022\/\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cul class=\u0022highwire-figure-links inline\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/11\/12\/9\/F1.large.jpg?download=true\u0022 class=\u0022highwire-figure-link highwire-figure-link-download\u0022 title=\u0022Download Figure 1.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload figure\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/11\/12\/9\/F1.large.jpg\u0022 class=\u0022highwire-figure-link highwire-figure-link-newtab\u0022 target=\u0022_blank\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EOpen in new tab\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/12533\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003Cdiv class=\u0022fig-caption attrib\u0022\u003E\u003Cspan class=\u0022fig-label\u0022\u003EFigure 1.\u003C\/span\u003E \n            \u003Cp id=\u0022p-10\u0022 class=\u0022first-child\u0022\u003EKaplan-Meier Curve of Survival Outcomes Among ITT Population.\u003C\/p\u003E\n         \u003Cq class=\u0022attrib\u0022 id=\u0022attrib-2\u0022\u003ESignificantly improved survival noted among patients treated with flucytosine-containing combination therapy (Arm II, green line) compared with amphotericin monotherapy (Arm I, blue line) at 70 days and 182 days.\u003C\/q\u003E\u003Cq class=\u0022attrib\u0022 id=\u0022attrib-3\u0022\u003EReproduced with permission from J. Day, MD.\u003C\/q\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-11\u0022\u003EDr. Day concluded by saying that in light of this research, improving access to amphotericin and flucytosine in regions where cryptococcal disease is prevalent, such as southeast Asia and Africa, has the potential to significantly reduce the global burden of deaths due to this devastating disease.\u003C\/p\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2011 MD Conference Express\u003C\/li\u003E\u003C\/ul\u003E\u003Cspan class=\u0022highwire-journal-article-marker-end\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Cspan id=\u0022related-urls\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Ca href=\u0022http:\/\/mdc.sagepub.com\/content\/11\/12\/9.abstract\u0022 class=\u0022hw-link hw-link-article-abstract\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView Summary\u003C\/a\u003E\u003C\/div\u003E  \u003C\/div\u003E\n\n  \n  \u003C\/div\u003E\n\u003C\/div\u003E\n  \u003C\/div\u003E\n\u003C\/div\u003E\n\u003C\/div\u003E\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_figures.js?nzm1fp\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_openurl.js?nzm1fp\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_tables.js?nzm1fp\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}