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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\u003EDarunavir is a protease inhibitor (PI) dosed as a single daily tablet. PIs have a high genetic barrier to resistance, but a PI-based single-tablet regimen has not been available. This article presents the results of the week 48 analysis of the Safety and Efficacy of Darunavir\/Cobicistat\/Emtricitabine\/GS-7340 Single Tablet Regimen Versus Cobicistat-Boosted Darunavir Plus Emtricitabine\/Tenofovir Disoproxil Fumarate Fixed Dose Combination in HIV-1 Infected, Antiretroviral Treatment Na\u00efve Adults [GS-US-299-0102; \u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT01565850\u0026amp;atom=%2Fspmdc%2F14%2F28%2F22.atom\u0022\u003ENCT01565850\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\u003C\/ul\u003E\u003Cul class=\u0022kwd-group clinical-trial\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003EInfectious Disease Clinical Trials\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EInfectious Disease\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EHIV \u0026amp; AIDS\u003C\/li\u003E\u003C\/ul\u003E\u003Cp id=\u0022p-2\u0022\u003ETenofovir disoproxil fumarate (TDF) is a safe and potent prodrug of the nucleotide reverse transcriptase inhibitor tenofovir; it is available as a single-tablet regimen; and it can be taken in combination with 3 of the 4 guideline-recommended third agents. Tenofovir alafenamide (TAF) is a novel tenofovir prodrug that provides higher intracellular tenofovir diphosphate levels and lower plasma tenofovir levels than TDF. Darunavir is a protease inhibitor (PI) dosed as a single daily tablet. PIs have a high genetic barrier to resistance, but a PI-based single-tablet regimen has not been available.\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003EAnthony Mills, MD, Southern California Men\u0027s Medical Group, Los Angeles, California, USA, presented the results of the week 48 analysis of the Safety and Efficacy of Darunavir\/Cobicistat\/Emtricitabine\/GS-7340 Single Tablet Regimen Versus Cobicistat-Boosted Darunavir Plus Emtricitabine\/Tenofovir Disoproxil Fumarate Fixed Dose Combination in HIV-1 Infected, Antiretroviral Treatment Na\u00efve Adults [GS-US-299-0102; \u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT01565850\u0026amp;atom=%2Fspmdc%2F14%2F28%2F22.atom\u0022\u003ENCT01565850\u003C\/a\u003E]. This phase 2 trial compared the combination of darunavir\/cobicistat\/emtricitabine\/TAF (D\/C\/F\/TAF) versus darunavir (DRV) boosted by cobicistat (COBI) and F\/TDF in treatment-na\u00efve HIV-infected adults.\u003C\/p\u003E\u003Cp id=\u0022p-4\u0022\u003EA total of 150 treatment-na\u00efve patients with HIV RNA \u2265 5000 copies\/mL, CD4 \u0026gt; 50, estimated glomerular filtration rate \u0026gt; 70 mL\/min, and a screening genotype with sensitivity to darunavir, TDF, and emtricitabine (F) were randomized to D\/C\/F\/TAF (n = 100) or DRV+ COBI+ F\/TDF (n = 50) once daily with matched placebos. The primary end point was HIV-1 RNA \u0026lt; 50 copies\/mL (virologic success) at week 24.\u003C\/p\u003E\u003Cp id=\u0022p-5\u0022\u003EAt week 24, there were similar proportions of patients in the D\/C\/F\/TAF and DRV + COBI + F\/TDF groups that achieved virologic success (75% vs 74%; weighted difference, 3.3; 95% CI, \u221211.4 to 18.1). At week 48, 77% of patients in the D\/C\/F\/TAF group versus 84% in the DRV + COBI + F\/TDF group had achieved virologic success (weighted difference \u22126.2; 95% CI, \u221219.9 to 7.4).\u003C\/p\u003E\u003Cp id=\u0022p-6\u0022\u003EOf 8 patients meeting the criteria for resistance analysis due to virologic rebound, none tested resistant to TDF, emtricitabine, or darunavir. The study drug was discontinued by 18% of D\/C\/F\/TAF patients and 16% of DRV + COBI + F\/TDF patients, but none of the discontinuations were efficacy related. Two patients in each arm discontinued due to adverse events (AEs). AEs in the D\/C\/F\/TAF versus the DRV + COBI + F\/TDF group were as follows: diarrhea (21% vs 26%), upper respiratory tract infection (16% vs 14%), fatigue (14% vs 18%), nausea (13% vs 10%), and rash (12% vs 8%).\u003C\/p\u003E\u003Cp id=\u0022p-7\u0022\u003EThe mean change in serum creatinine at week 48 was + 0.06 mg\/dL in the D\/C\/F\/TAF group and + 0.09 mg\/dL in the DRV + COBI + F\/TDF group (\u003Cem\u003EP\u003C\/em\u003E = .053). Renal tubular proteinuria rates were significantly lower in the D\/C\/F\/TAF group (retinol binding protein:creatinine ratio, \u003Cem\u003EP\u003C\/em\u003E = .003; \u03b2-2 microglobulin:creatinine ratio, \u003Cem\u003EP\u003C\/em\u003E = .002).\u003C\/p\u003E\u003Cp id=\u0022p-8\u0022\u003EAt week 48, in the D\/C\/F\/TAF group versus the DRV + COBI + F\/TDF group, the median changes in fasting metabolic assessments were as follows: total cholesterol (40 vs 5 mg\/dL, \u003Cem\u003EP\u003C\/em\u003E \u0026lt; .001), low-density lipoprotein (26 vs 4 mg\/dL, \u003Cem\u003EP\u003C\/em\u003E \u0026lt; .001), high-density lipoprotein (7 vs 3 mg\/dL, \u003Cem\u003EP\u003C\/em\u003E = .009); total cholesterol:high-density lipoprotein ratio (0.0 vs \u22120.2, \u003Cem\u003EP\u003C\/em\u003E = .15), triglycerides (29 vs \u22125 mg\/dL, \u003Cem\u003EP\u003C\/em\u003E = .007), and serum glucose (5 vs 2 mg\/dL, \u003Cem\u003EP\u003C\/em\u003E = .33). Patients in the D\/C\/F\/TAF group had a significantly lower mean percent age change in bone mineral density of the hip (\u003Cem\u003EP\u003C\/em\u003E \u2264 .001) and spine (\u003Cem\u003EP\u003C\/em\u003E = .003) at week 48.\u003C\/p\u003E\u003Cp id=\u0022p-9\u0022\u003EAt week 48, viral suppression rates were the same in both study groups, and no patients had developed drug resistance. Both regimens were well tolerated, with similarly low rates of AE-related discontinuation. Dr Mills concluded that the improved renal and bone profiles of TAF and the high-resistance barrier of darunavir warrant a phase 3 study of a single-tablet regimen of D\/C\/F\/TAF.\u003C\/p\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2014 MD Conference Express\u00ae\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\/14\/28\/22.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_openurl.js?nzm17d\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}