{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,24]],"date-time":"2025-09-24T10:30:34Z","timestamp":1758709834344},"reference-count":23,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2009,1,20]],"date-time":"2009-01-20T00:00:00Z","timestamp":1232409600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["HIV Medicine"],"published-print":{"date-parts":[[2009,2]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>This phase IIb study explored the antiviral activity and safety of the investigational CC chemokine receptor 5 (CCR5) antagonist aplaviroc (APL) in antiretroviral\u2010na\u00efve patients harbouring R5\u2010 or R5X4\u2010tropic virus.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A total of 191 patients were randomized 2:2:2:1 to one of three APL dosing regimens or to lamivudine (3TC)\/zidovudine (ZDV) twice daily (bid), each in combination with lopinavir\/ritonavir (LPV\/r) 400\u2003mg\/100\u2003mg bid. Efficacy, safety and pharmacokinetic parameters were assessed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>This study was terminated prematurely because of APL\u2010associated idiosyncratic hepatotoxicity. A total of 141 patients initiated treatment early enough to have been able to complete 12 weeks on treatment [modified intent\u2010to\u2010treat (M\u2010ITT) population]; of these, 133 completed the 12\u2010week treatment phase. The proportion of subjects in the M\u2010ITT population with HIV\u20101 RNA &lt;400\u2003copies\/mL at week 12 was 50, 48, 54 and 75% in the APL 200\u2003mg bid, APL 400\u2003mg bid, APL 800\u2003mg once a day (qd) and 3TC\/ZDV arms, respectively. Similar responses were seen in the few subjects harbouring R5X4\u2010tropic virus (<jats:italic>n<\/jats:italic>=17). Common clinical adverse events (AEs) were diarrhoea, nausea, fatigue and headache. APL demonstrated nonlinear pharmacokinetics with high interpatient variability.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>While target plasma concentrations of APL were achieved, the antiviral activity of APL+LPV\/r did not appear to be comparable to that of 3TC\/ZDV+LPV\/r.<\/jats:p><\/jats:sec>","DOI":"10.1111\/j.1468-1293.2008.00660.x","type":"journal-article","created":{"date-parts":[[2009,1,20]],"date-time":"2009-01-20T05:35:22Z","timestamp":1232429722000},"page":"116-124","source":"Crossref","is-referenced-by-count":14,"title":["Antiviral activity and safety of aplaviroc, a CCR5 antagonist, in combination with lopinavir\/ritonavir in HIV\u2010infected, therapy\u2010na\u00efve patients: results of the EPIC study (CCR100136)<sup>*<\/sup>"],"prefix":"10.1111","volume":"10","author":[{"given":"P","family":"Yeni","sequence":"first","affiliation":[]},{"given":"A","family":"LaMarca","sequence":"additional","affiliation":[]},{"given":"D","family":"Berger","sequence":"additional","affiliation":[]},{"given":"P","family":"Cimoch","sequence":"additional","affiliation":[]},{"given":"A","family":"Lazzarin","sequence":"additional","affiliation":[]},{"given":"P","family":"Salvato","sequence":"additional","affiliation":[]},{"given":"FM","family":"Smaill","sequence":"additional","affiliation":[]},{"given":"E","family":"Teofilo","sequence":"additional","affiliation":[]},{"given":"SJ","family":"Madison","sequence":"additional","affiliation":[]},{"given":"WG","family":"Nichols","sequence":"additional","affiliation":[]},{"given":"KK","family":"Adkison","sequence":"additional","affiliation":[]},{"given":"T","family":"Bonny","sequence":"additional","affiliation":[]},{"given":"J","family":"Millard","sequence":"additional","affiliation":[]},{"given":"D","family":"McCarty","sequence":"additional","affiliation":[]},{"name":"the EPIC (CCR100136) study team","sequence":"additional","affiliation":[]}],"member":"311","published-online":{"date-parts":[[2009,1,20]]},"reference":[{"key":"e_1_2_6_2_2","first-page":"253","article-title":"gp120","volume":"19","author":"Poignard P","year":"2001","journal-title":"biologic aspects of structural features"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1196-1240"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1296-1293"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.78.16.8654-8662.2004"},{"key":"e_1_2_6_6_2","unstructured":"NakataH MaedaK KawanoYet al. Potentin vivoanti\u2010R5HIV effects of AK602 a novel spirodiketopiperazine (SPD)\u2010containing HIV\u2010specific CCR5 inhibitor in hu\u2010PBMC\u2010NOD\u2010mice.10th Conference on Retroviruses and Opportunistic Infections. Boston MA February 2003 [Abstract 564a]."},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.aids.0000183633.06580.8a"},{"key":"e_1_2_6_8_2","unstructured":"SparksS AdkisonK Shachoy\u2010ClarkA PiscitelliS DemarestJ.Prolonged duration of CCR5 occupancy by 873140 in HIV\u2010negative and HIV\u2010positive W.12th Conference on Retroviruses and Opportunistic Infections. 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Denver CO February 2006 [Abstract 161LB]."},{"key":"e_1_2_6_19_2","unstructured":"KitrinosKM IrlbeckDM LaBrancheCC MadsenHA DemarestJF.Virologic characterization of treatment na\u00efve subjects failing an aplaviroc\u2010based regimen with either lamivudine\/zidovudine or lopinavir\/ritonavir.15th International Drug Resistance Workshop. Sitges Spain June 2006 [Abstract 21]."},{"key":"e_1_2_6_20_2","first-page":"651","article-title":"GW433908\/ritonavir once daily in antiretroviral therapy\u2010na\u00efve HIV\u2010infected patients","volume":"18","author":"MacManus S","year":"2004","journal-title":"absence of protease resistance at 48 weeks"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1086\/380509"},{"key":"e_1_2_6_22_2","unstructured":"Selzentry (maraviroc) Product Information Pfizer Inc. 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