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type=\u0022text\/css\u0022 rel=\u0022stylesheet\u0022 href=\u0022\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/advagg_css\/css__ce2QY63WIanKyr8eSq7eavr1XQRRmFD6ZSmwpyJi8lM__zXwFqpqmxrZOXXcd_TpBQpjuELbmIP9wBR5UuTDWAO4__YJWWMMdfCJuAFm5cUEp88OsodhO3ZA-2lzRfoBsSlk4.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\u003ECurrent guidelines recommend non-nucleoside reverse transcriptase inhibitor (NNRTI)-based, boosted protease inhibitor (PI)-based, and integrase strand transfer inhibitor (INSTI)-based regimens for the treatment of HIV [\u003Ca href=\u0022http:\/\/aidsinfo.nih.gov\/Guidelines\/HTML\/1\/adult-and-adolescent-treatment-guidelines\/0\u0022\u003Ehttp:\/\/aidsinfo.nih.gov\/Guidelines\/HTML\/1\/adult-and-adolescent-treatment-guidelines\/0\u003C\/a\u003E; Thompson MA et al. \u003Cem\u003EJAMA\u003C\/em\u003E 2012]. This article discusss recent data from clinical trials comparing initial antiretroviral regimens and factors to be considered when starting antiretroviral therapy.\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003EFeatured Meeting - Specialty page\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003ESexually Transmitted Diseases\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EHIV \u0026amp; AIDS\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EEmerging Therapies\u003C\/li\u003E\u003C\/ul\u003E\u003Cp id=\u0022p-2\u0022\u003ECurrent guidelines recommend non-nucleoside reverse transcriptase inhibitor (NNRTI)-based, boosted protease inhibitor (PI)-based, and integrase strand transfer inhibitor (INSTI)-based regimens for the treatment of HIV [\u003Ca href=\u0022http:\/\/aidsinfo.nih.gov\/Guidelines\/HTML\/1\/adult-and-adolescent-treatment-guidelines\/0\u0022\u003Ehttp:\/\/aidsinfo.nih.gov\/Guidelines\/HTML\/1\/adult-and-adolescent-treatment-guidelines\/0\u003C\/a\u003E; Thompson MA et al. \u003Cem\u003EJAMA\u003C\/em\u003E 2012]. Joel E. Gallant, MD, MPH, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA, discussed recent data from clinical trials comparing initial antiretroviral regimens and factors to be considered when starting antiretroviral therapy (ART).\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003EThe ECHO and THRIVE trials were similar studies that compared the NNRTIs rilpivirine (RPV) and efavirenz (EFV) in antiretroviral-na\u00efve HIV-1-infected adults. In a pooled analysis of data from these trials, viral suppression with RPV (25 mg QD) and EFV (600 mg QD) was comparable at Week 96 (78% in each arm). RPV was associated with more virologic failures but fewer discontinuations due to adverse events than EFV [Cohen CJ et al. IAS 2011 Poster TULBPE032].\u003C\/p\u003E\u003Cp id=\u0022p-4\u0022\u003ERaltegravir (RAL) is an INSTI that has been compared with EFV in treatment-na\u00efve patients. STARTMRK was a 5-year Phase 3 trial that reported noninferiority for RAL at 48 and 96 weeks, and superiority (71.0% vs 61.3% at Week 240 in patients with viral load \u0026lt;50 copies\/mL; difference 9.5; 95% CI, 1.7 to 17.3; p\u0026lt;0.001) at 4 and 5 years of follow-up, largely driven by higher side effect-related discontinuations in the EFV arm [Rockstroh J et al. IAC 2012 Abstract LBPE19]. Virologic suppression is more rapid with RAL\u2014an observation of uncertain clinical significance. As with NNRTIs, resistance is more likely to emerge with treatment failure of RAL than with ritonavir-boosted PI (PI\/r)-based regimens.\u003C\/p\u003E\u003Cp id=\u0022p-5\u0022\u003EThe INSTI elvitegravir (EVG) has been coformulated with the pharmacoenhancer cobicistat (COBI), emtricitabine (FTC), and tenofovir DF (TDF) in a single once-daily tablet, sometimes referred to as the \u003Cem\u003Equad\u003C\/em\u003E. In a pooled analysis of two Phase 3 and one Phase 2 randomized controlled trials, the quad demonstrated high rates of virologic suppression when compared with EFV\/FTC\/TDF and atazanavir\/ritonavir (ATV\/r) plus FTC\/TDF with a slightly improved adverse event profile. Due to COBI\u0027s inhibition of renal creatinine tubular secretion, there were small increases in creatinine observed early in therapy with the quad; however, these stabilized through Week 48 [Ward D et al. ICAAC 2012 Abstract H-555]. In terms of resistance, failure on the quad can result in integrase mutations, while failure on EFV\/FTC\/TDF can lead to NNRTI mutations [Sax P et al. \u003Cem\u003ELancet\u003C\/em\u003E 2012]; those failing ATV\/r plus FTC\/TDF did not develop mutations [DeJesus E et al. \u003Cem\u003ELancet\u003C\/em\u003E 2012].\u003C\/p\u003E\u003Cp id=\u0022p-6\u0022\u003EWith respect to PIs, Dr. Gallant noted that the 800-mg tablet of darunavir is coming soon, as are DRV\/COBI and ATV\/COBI coformulations. In the future, a single-tablet PI formulation (DRV\/COBI\/GS7340\/COBI) is expected.\u003C\/p\u003E\u003Cp id=\u0022p-7\u0022\u003ERegarding nucleoside reverse transcriptase inhibitors (NRTIs), there have been some changes in the recommendations for abacavir (ABC). The combination of ABC and lamivudine (3TC) is now a recommended NRTI backbone in the IAS-USA guidelines for patients with negative HLA B*5701 assays and baseline viral loads \u0026lt;100,000 copies\/mL; it remains an alternative backbone in the United States Department of Health and Human Services guidelines. AIDS Clinical Trials Group Study A5202 found a greater difference in efficacy based on pretreatment CD4 count and viral load with ABC\/3TC compared with FTC\/TDF [Grant P et al. CROI 2011 Abstract 535]. Adding to this concern have been conflicting reports concerning the risk of myocardial infarction with ABC. Dr. Gallant noted that TDF is not without risks, particularly kidney disease [Scherzer R et al. \u003Cem\u003EAIDS\u003C\/em\u003E 2012] and a greater reduction in bone density than is seen with other agents, with a possible association with increased risk of bone fracture [Bedimo R et al. \u003Cem\u003EAIDS\u003C\/em\u003E 2012]. He closed his presentation with a review of single-tablet regimens (\u003Ca id=\u0022xref-table-wrap-1-1\u0022 class=\u0022xref-table\u0022 href=\u0022#T1\u0022\u003ETable 1\u003C\/a\u003E).\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\/12895\/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\/12895\/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\/12895\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-8\u0022 class=\u0022first-child\u0022\u003ESingle-Tablet Regimens.\u003C\/p\u003E\n         \u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-10\u0022\u003EDespite the availability of more than 25 antiretrovirals (ARVs), the number of recommended drug combinations remains limited for first-line ARV therapy and for switching to maintenance therapy. Patrick G. Yeni, MD, Bichat Medical School, Paris, France, said that there is a need for more drugs and strategies to accommodate very diverse individual constraints. Prof. Yeni would like to see an alternative to the conventional 3-drug combination regimen that replaces the 2 NRTI backbone, in particular in patients with boosted PI based-therapy. PI\/r containing NRTI sparing regimens might include PI\/r plus NNRTI, PI\/r plus CCR5 inhibitor, PI\/r plus INSTI, or PI\/r mono (dual) therapy. The results of a recently completed meta-analysis suggests that virologically well-suppressed HIV-infected patients have a lower chance to maintain viral suppression when switching from combined ART to PI\/r monotherapy [Mathis S et al. \u003Cem\u003EPLoS One\u003C\/em\u003E 2011]. However, the consequences of failing this therapy may not be critical as there are some data indicating that the virus remains fully sensitive to PI and that the viral load returns to undetectable levels after the addition of the original baseline NRTIs.\u003C\/p\u003E\u003Cp id=\u0022p-11\u0022\u003EProf. Yeni discussed 3 ARV drugs that are currently in Phase 3 clinical development: EVG, dolutegravir (DTG), and COBI. Results from a study that compared the efficacy and safety of EVG with RAL in patients who failed previous ARV therapy showed similar efficacy and safety. The researchers concluded that since EVG can be given once daily versus twice daily for RAL, it might improve adherence [Molina JM et al. \u003Cem\u003ELancet Infect Dis\u003C\/em\u003E 2012].\u003C\/p\u003E\u003Cp id=\u0022p-12\u0022\u003EIn the SPRING-2 study [\u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT01227824\u0026amp;atom=%2Fspmdc%2F12%2F14%2F19.atom\u0022\u003ENCT01227824\u003C\/a\u003E], a Phase 3 randomized, noninferiority study in treatment-na\u00efve patients, once-daily DTG has been shown to be noninferior to twice-daily RAL when coadministered with 2 NRTIs over 48 weeks. The safety profiles were comparable. Adjusted treatment difference for DTG (88%) versus RAL (85%) was 2.5% (95% CI, \u22122.2 to 7.1). At virologic failure, no integrase nor NRTI mutations were detected in the DTG arm [Raffi F et al. IAC 2012 Abstract THLBB04]. In the Phase 3 SINGLE study [\u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT01263015\u0026amp;atom=%2Fspmdc%2F12%2F14%2F19.atom\u0022\u003ENCT01263015\u003C\/a\u003E], the combination of DTG with ABC\/3TC was shown to be superior to the fixed-dose combination TDF\/FTC\/EFV at 48 weeks, with less frequent discontinuation in the DTG arm [Walmsley S et al. ICAAC 2012 Abstract H-556b].\u003C\/p\u003E\u003Cp id=\u0022p-13\u0022\u003ECOBI has no ARV activity, but \u003Cem\u003Ein vitro\u003C\/em\u003E it is a potent and specific CYP3A inhibitor and inhibitor of MATE1 tubular transporter of creatinine. In a 48-week Phase 3 randomized study, FTC\/TDF plus ATV\/COBI was noninferior to FTC\/TDF plus ATV\/r in ART-na\u00efve patients [Gallant JE et al. IAC 2012 Abstract TUAB0103]. The COBI arm had more Grade 3\u20134 hyperbilirubinemia (65% vs 57%; p=0.023) and more profound decreases in estimated glomerular filtration rate (\u221213 vs \u22129 mL\/min; p=0.001) versus the ATV\/r arm, but there was no PI resistance in the COBI group at 48 weeks.\u003C\/p\u003E\u003Cp id=\u0022p-14\u0022\u003EProf. Yeni concluded by noting that that several ARTs are in Phase 1 or 2 (\u003Ca id=\u0022xref-table-wrap-2-1\u0022 class=\u0022xref-table\u0022 href=\u0022#T2\u0022\u003ETable 2\u003C\/a\u003E), and \u201calthough the clinical application of individualized ARV therapy is improving, new drugs and strategies need to be tested.\u201d\u003C\/p\u003E\u003Cdiv id=\u0022T2\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\/12896\/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\/12896\/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\/12896\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 2.\u003C\/span\u003E \n            \u003Cp id=\u0022p-15\u0022 class=\u0022first-child\u0022\u003ESome Antiretroviral Agents in Phase 1 or 2 Development. Class Agent Phase NRTIs\u003C\/p\u003E\n         \u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2012 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\/12\/14\/19.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?nzn9f1\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?nzn9f1\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}