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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\u003EThis article discusses studies that have shown the effectiveness of new and potential antiretroviral therapy therapies for the treatment of HIV infection, including single-tablet regimens, coformulations, nucleoside reverse transcriptase inhibitor-sparing regimens, CCR5 antagonists as initial therapy, and new entry inhibitors.\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003ESexually Transmitted Diseases\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EEmerging Therapies\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EHIV \u0026amp; AIDS\u003C\/li\u003E\u003C\/ul\u003E\u003Cp id=\u0022p-2\u0022\u003EImprovements in antiretroviral therapy (ART) have made the treatment of HIV infection more potent and better tolerated. While current treatment regimens still have limitations, they are more effective, more convenient, and less toxic than those that were used in the early ART era. Joel E. Gallant, MD, MPH, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA, discussed studies that have shown the effectiveness of new and potential ART therapies, including single-tablet regimens, coformulations, nucleoside reverse transcriptase inhibitor (NRTI)-sparing regimens, CCR5 antagonists as initial therapy, and new entry inhibitors.\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003EECHO [\u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT00540449\u0026amp;atom=%2Fspmdc%2F11%2F12%2F15.atom\u0022\u003ENCT00540449\u003C\/a\u003E] and THRIVE [\u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT00543725\u0026amp;atom=%2Fspmdc%2F11%2F12%2F15.atom\u0022\u003ENCT00543725\u003C\/a\u003E], two randomized Phase 3 trials, showed that the recently approved non-nucleoside reverse transcriptase inhibitor (NNRTI) rilpivirine (RPV) has sustained efficacy that is noninferior to efavirenz (EFV) in ART-na\u00efve adults who are infected with HIV-1 [Cohen CJ et al. \u003Cem\u003ELancet\u003C\/em\u003E 2011; Molina JM et al. \u003Cem\u003ELancet\u003C\/em\u003E 2011]. There were fewer discontinuations that were due to adverse events and fewer treatment-limiting side effects (especially neurological and dermatological) in the RPV arm but more virological failure and resistance compared with the EFV arm, most notably in participants with baseline viral loads \u0026gt;100,000 copies\/mL (\u003Ca id=\u0022xref-fig-1-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F1\u0022\u003EFigure 1\u003C\/a\u003E). RPV has been approved both as a single agent and in a coformulation with tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC). It is taken once daily with a meal and is contraindicated in patients who are taking proton pump inhibitors.\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\/15\/F1.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022ECHO\/THRIVE Outcomes.\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-727396706\u0022 data-figure-caption=\u0022ECHO\/THRIVE Outcomes.\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\/15\/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\/15\/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\/15\/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\/12442\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-4\u0022 class=\u0022first-child\u0022\u003EECHO\/THRIVE Outcomes.\u003C\/p\u003E\n         \u003Cq class=\u0022attrib\u0022 id=\u0022attrib-1\u0022\u003EReproduced with permission from The \u003Cem\u003ELancet.\u003C\/em\u003E Rilpivirine versus efavirenz with tenofovir and emtricitabine in treatment-naive adults infected with HIV-1 (ECHO): a phase 3 randomised double-blind active-controlled trial. Molina JM et al. July 16, 2011;378(9787)238\u2013246.\u003C\/q\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-5\u0022\u003EIn the MERIT study [\u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT00098293\u0026amp;atom=%2Fspmdc%2F11%2F12%2F15.atom\u0022\u003ENCT00098293\u003C\/a\u003E], maraviroc (MVC) BID was not noninferior to EFV at \u0026lt;50 copies\/mL in the primary analysis in ART-na\u00efve patients with CCR5-tropic virus. However, 15% of patients in the original MERIT trial had dual\/mixed-tropic virus, using the more sensitive tropism assay. After exclusion of data from those patients, the MVC arm met noninferiority criteria compared with EFV [Cooper DA et al. \u003Cem\u003EJ Infect Dis\u003C\/em\u003E 2010] (\u003Ca id=\u0022xref-fig-2-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F2\u0022\u003EFigure 2\u003C\/a\u003E). QD administration of MVC is also being studied. In a post hoc analysis from the original MOTIVATE trials, which initially included a QD MVC arm, virological suppression was comparable in patients who were treated with MVC QD and BID. MVC has been approved for initial therapy. Potential advantages include its excellent tolerability, its high barrier to resistance, and the fact that treatment-na\u00efve patients are more likely to have CCR5-tropic virus than treatment-experienced patients. The main disadvantage is the need for baseline tropism testing.\u003C\/p\u003E\u003Cdiv id=\u0022F2\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\/15\/F2.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022Virological and Immunological Outcomes.\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-727396706\u0022 data-figure-caption=\u0022Virological and Immunological Outcomes.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003E\u003Cimg class=\u0022fragment-image\u0022 alt=\u0022Figure 2.\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/11\/12\/15\/F2.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\/15\/F2.large.jpg?download=true\u0022 class=\u0022highwire-figure-link highwire-figure-link-download\u0022 title=\u0022Download Figure 2.\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\/15\/F2.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\/12444\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 2.\u003C\/span\u003E \n            \u003Cp id=\u0022p-6\u0022 class=\u0022first-child\u0022\u003EVirological and Immunological Outcomes.\u003C\/p\u003E\n         \u003Cq class=\u0022attrib\u0022 id=\u0022attrib-2\u0022\u003EReproduced with permission from JE Gallant, MD, MPH.\u003C\/q\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-7\u0022\u003EA variety of \u201cnucleoside-sparing regimens\u201d have been studied in clinical trials, though none to date has demonstrated sufficient efficacy and\/or tolerability to make it a standard-of-care regimen. Examples that have been studied to date include combinations of a boosted protease inhibitor plus EFV, raltegravir (RAL), or MVC.\u003C\/p\u003E\u003Cp id=\u0022p-8\u0022\u003EElvitegravir (EVG) is an investigational integrase inhibitor that requires pharmacological \u201cboosting\u201d by either ritonavir (RT) or cobicistat (COBI), an experimental pharmacokinetic enhancer, or \u201cbooster.\u201d Phase 2 data suggested that a \u2018quad\u2019 regimen of once-daily EVG\/COBI\/FTC\/tenofovir disoproxil fumarate (TDF) achieves and maintains a high rate of virological suppression with fewer central nervous system and psychiatric adverse effects compared with the current standard-of-care regimen (EFV\/FTC\/TDF) [Cohen C. \u003Cem\u003EAIDS\u003C\/em\u003E 2011], and a similarly designed Phase 3 study apparently shows noninferiority of the \u201cquad\u201d compared with EFV, with similar discontinuation rates due to adverse events in both arms [Gilead press release. August 15, 2011]. A study that compared EVG with raltegravir (RAL) in treatment-experienced patients found that EVG was noninferior to RAL [Molina JM. IAS 2011 Rome]. COBI is also being studied as a booster for protease inhibitors. In a Phase 2 trial, the efficacy of a COBI-boosted atazanavir (ATV)-based regimen was similar to that of a RT-boosted ATV-based regimen [Cohen C. \u003Cem\u003EAIDS\u003C\/em\u003E 2011]. Cobicistat is associated with a modest increase in serum creatinine, with a resulting decrease in estimated glomerular filtration rate (GFR), but not measured GFR. This appears to be due to its effect on creatinine transport by the renal tubules rather than to true nephrotoxicity [German P. ICAAC 2011; Lepist EI. ICAAC 2011].\u003C\/p\u003E\u003Cp id=\u0022p-9\u0022\u003EDolutegravir (DTG) is another promising integrase inhibitor. In the SPRING-1 trial, which was conducted in ART-na\u00efve patients, it was noninferior to EFV with better tolerability [van Lunzen J. IAS 2011 Rome]. There was no selection of integrase mutations in patients who failed, and tolerability was better than with EFV. As with COBI, DTG decreases estimated GFR but not actual GFR, by a mechanism that is similar to that of COBI [Koteff J et al. ICAAC 2011]. DTG may have some activity against RAL- or EVG-resistant virus, especially when dosed twice daily [Eron J. CROI 2011].\u003C\/p\u003E\u003Cp id=\u0022p-10\u0022\u003EGS-7340 is a new tenofovir prodrug that achieves higher intracellular tenofovir levels with lower plasma levels compared with TDF [Markowitz M. CROI 2011]. The hope is that it will be more potent than TDF at smaller doses with less nephrotoxicity.\u003C\/p\u003E\u003Cp id=\u0022p-11\u0022\u003ELersivirine (LRV) is an investigational NNRTI that had overall efficacy that was similar to that of EFV in a Phase 2 study of treatment-na\u00efve patients [Pozniak A. IAS 2011]. Efficacy was lower in patients with viral loads \u0026gt;100,000 copies\/mL. The incidence of grade 3 and 4 adverse events was higher in the EFV arm, although nausea and headache were common with LRV.\u003C\/p\u003E\u003Cp id=\u0022p-12\u0022\u003EThere are a number of potential HIV entry inhibitors that can act at various stages of HIV development, such as coreceptor binding, and virus-cell fusion. They include BMS-663068, an oral HIV attachment inhibitor; ibalizumab, an HIV-neutralizing monoclonal antibody; and cenicriviroc, a CCR5 antagonist with anti-CCR2 activity.\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\/15.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?nzmx5d\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?nzmx5d\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}