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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\u003EBMS-986001 is a novel nucleoside analog reverse-transcriptase inhibitor that, in higher doses, demonstrated comparable efficacy to tenofovir in treatment-na\u00efve HIV-1-infected subjects. This article presents the results of this phase 2b randomized dose trial (active controlled, blinded to BMS-986001) with worldwide recruitment.\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\u003EBMS-986001 is a novel nucleoside analog reverse-transcriptase inhibitor (NRTI) that, in higher doses, demonstrated comparable efficacy to tenofovir (TDF) in treatment-na\u00efve HIV-1-infected subjects. Samir Gupta, MD, Indiana University School of Medicine, Indianapolis, Indiana, United States, presented the results of this phase 2b randomized dose trial (active controlled, blinded to BMS-986001) with worldwide recruitment.\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003EBMS-986001 was developed to better target viral transcription and minimize the toxicities associated with current NRTIs, such as increased risk of osteoporotic fracture [Bedimo R et al. \u003Cem\u003EAIDS\u003C\/em\u003E. 2012], renal dysfunction [Scherzer R et al. \u003Cem\u003EAIDS\u003C\/em\u003E. 2012], and adverse metabolic outcomes [Hammond E et al. \u003Cem\u003EClin Infect Dis.\u003C\/em\u003E 2010]. It is active against some HIV-1 isolates with NRTI resistance-associated mutations, including the K65R and L74V substitutions and the Q151M constellation (without M184V) [Li Z et al. \u003Cem\u003EAntimicrob Agents Chemother\u003C\/em\u003E. 2013]. In a previous study [Cotte L et al. \u003Cem\u003EJ Acquir Immune Defic Syndr.\u003C\/em\u003E 2013], BMS-986001 administration for 10 days led to substantial decreases in plasma HIV-1 RNA levels and was well tolerated.\u003C\/p\u003E\u003Cp id=\u0022p-4\u0022\u003EIn this study, the safety and efficacy of BMS-986001 (100, 200, and 400 mg QD) was compared with TDF (300 mg QD) in treatment-na\u00efve subjects with HIV-1. All subjects also received 600 mg of efavirenz (EFV) plus 300 mg of lamivudine (3TC) QD. The primary study end points were the efficacy and safety of BMS-986001 at week 24, determined by measuring the proportions of subjects with plasma HIV-1 RNA \u0026lt; 50 counts\/mL and the number of adverse events (AEs). Secondary end points included the efficacy and safety of BMS-986000 through week 48, change from baseline in CD4-positive T-cell count through weeks 24 and 48, and the number of subjects experiencing virologic failure with treatment-emergent resistance-associated mutations through weeks 24 and 48.\u003C\/p\u003E\u003Cp id=\u0022p-5\u0022\u003EPatients were included in the study if they were \u2265 18 years of age and antiretroviral treatment na\u00efve and if they had plasma HIV-1 RNA \u0026gt; 5000 counts\/mL and a CD4-positive T-cell count \u0026gt; 200 cells\/mm\u003Csup\u003E3\u003C\/sup\u003E. The exclusion criteria were resistance to 3TC, EFV, TDF, or protease inhibitors or a positive test for hepatitis B surface antigen or hepatitis C antibodies\/RNA.\u003C\/p\u003E\u003Cp id=\u0022p-6\u0022\u003EBaseline demographics and characteristics in the modified intent-to-treat population (received 1 dose of study drug) were similar among the 4 groups. Subjects age ranged between 29 and 34 years, and the majority were men (62% to 71%). HIV subtypes included AE, B, and C, reflecting the worldwide distribution of the subjects. Median HIV-1 RNA (log\u003Csub\u003E10\u003C\/sub\u003E counts\/mL) was 4.4, with \u223c 18% having \u2265 100 000 counts\/mL. Median CD4-positive T-cell count (cells\/\u03bcL) was 312, with \u223c 8% having \u0026lt; 200 cells\/\u03bcL.\u003C\/p\u003E\u003Cp id=\u0022p-7\u0022\u003EThe proportion of subjects achieving HIV-1 RNA \u0026lt; 50 counts\/mL at weeks 24 and 48 was similar among treatment groups in the modified intent-to-treat population analysis. In the BMS-986000 group, these rates at weeks 24 and 48 were, respectively, 88% and 75% in the 100-mg arm, 81% and 81% for the 200-mg arm, and 95% and 89% for the 400-mg arm. In the TDF group, these rates at weeks 24 and 48 were 89% and 82%, respectively. The observed mean change in CD4-positive T-cell counts was similar from baseline through weeks 24 (about 100 to 150 cells\/\u03bcL) and 48 (about 150 to 190 cells\/\u03bcL).\u003C\/p\u003E\u003Cp id=\u0022p-8\u0022\u003EEmergent resistance\/reduced susceptibility to the study drug was higher in patients receiving BMS-986000, particularly with the 100-mg dose (14% vs 6% in the 200- and 400-mg dose groups and 1% in the TDF group). The occurrence of serious AEs was similar in the 4 groups. There were no noticeable trends for grade 2 to 4 related AEs or new\/unexpected safety signals for TDF; 1 patient died (nonstudy related). Higher doses of BMS-986001 demonstrated comparable efficacy to TDF when combined with EFV + 3TC in treatment-na\u00efve HIV-1-infected subjects.\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\/16.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?nzl6f2\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}