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  15th CROI
Conference on Retroviruses and Opportunistic Infections Boston, MA
Feb 3-6, 2008
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Do Lipid Signals Favor Maraviroc Over Efavirenz in Untreated People?
  15th Conference on Retroviruses and Opportunistic Infections
February 3-6, 2008
Mark Mascolini
(Poster online at http://www.retroconference.org/2008/PDFs/929.pdf.)
People starting a first-line regimen hinged on the CCR5 antagonist maraviroc had better 48-week lipid and heart risk profiles than people starting an efavirenz regimen in the ongoing MERIT trial [1]. At this point maraviroc is licensed only for treatment-experienced patients.
Although people randomized to twice-daily maraviroc plus Combivir gained more CD4 cells than those randomized to efavirenz plus Combivir in MERIT, an as-treated analysis determined that 65% taking maraviroc versus 69% taking efavirenz had a 48-week viral load below 50 copies presented during the summer at the international conference in Sydney [2]. According to the trial's statistical rules, that result meant maraviroc is "not noninferior" to efavirenz as first-line therapy in this study population. But a new analysis presented by Pfizer at CROI 2008 found that when considering tropism switches from R5 to X4 between study screening baseline efavirenz and maraviroc had similar percentages below 50 copies.
The lipid analysis compared pretreatment and 48-week lipids in 360 people randomized to maraviroc and 361 randomized to efavirenz [1]. Pretreatment lipid profiles matched closely in the maraviroc and efavirenz arms, with median values of 155 and 156 mg/dL for total cholesterol, 88 and 92 mg/dL for dangerous low-density lipoprotein (LDL) cholesterol, 38 and 37 mg/dL for "good" high-density lipoprotein (HDL) cholesterol, 4.0 and 4.2 for total-to-HDL ratio, and 104 and 106 mg/dL for triglycerides. About 50 people in each treatment arm (14%) had starting cholesterol and triglyceride quotients above the National Cholesterol Education Program (NCEP) cutoffs for starting antilipid therapy.
Median maximum change in total, HDL, and LDL cholesterol and triglycerides proved significantly greater with efavirenz plus Combivir than with maraviroc plus Combivir (P < 0.0001 for all cholesterol levels, P = 0.0002 for triglycerides). Week-48 LDL readings stood at or above 160 mg/dL in 31 people (9%) taking efavirenz and 3 (0.9%) taking maraviroc (P < 0.0001). More people taking efavirenz than maraviroc reached lipid scores that call for LDL-lowering therapy in NCEP guidelines:
· Total cholesterol > 200 mg/dL: 31.4% efavirenz, 8.2% maraviroc, P < 0.0001
· LDL cholesterol > 130 mg/dL: 21.5% efavirenz, 4.6% maraviroc, P < 0.0001
· LDL cholesterol > 160 mg/dL: 9.0% efavirenz, 0.9% maraviroc, P < 0.0001
· Triglycerides > 200 mg/dL: 13.7% efavirenz, 11.1% maraviroc (not significant)
Nonetheless, similarly low proportions in each treatment arm-6 taking efavirenz and 3 taking maraviroc-actually started anti-LDL therapy during the study. Total-to-HDL cholesterol ratio fell slightly but significantly more from baseline with maraviroc (median maximum change -0.5, interquartile range -1 to +0.2) than with efavirenz (median maximum change -0.4, interquartile range -1 to +05) (P < 0.01). Before treatment and at last follow-up, median ratios stood below an ideal score of <4.5 in both groups.
Absolute 10-year coronary heart disease projection by the Framingham score favored maraviroc over efavirenz at 24 weeks (2.1% versus 3.0%) and 48 weeks (2.2% versus 3.3%). Although these differences are small, study statisticians calculated that people taking maraviroc had about a 30% lower 10-year relative risk of coronary heart disease than people taking efavirenz, a significant benefit.
1. DeJesus E, Walmsley S, Cohen C, et al. Fasted lipid changes after administration of maraviroc or efavirenz in combination with zidovudine and lamivudine for 48 weeks to treatment-naive HIV-infected patients. 15th Conference on Retroviruses and Opportunistic Infections. February 3-6, 2008. Boston. Abstract 791.
2. Saag M, Ive P, Heera J, et al. A multicenter, randomized, double-blind, comparative trial of a novel CCR5 antagonist, maraviroc versus efavirenz, both in combination with Combivir (zidovudine/lamivudine), for the treatment of antiretroviral naive subjects infected with R5 HIV-1: week 48 results of the MERIT study. 4th IAS Conference on HIV Pathogenesis, Treatment, and Prevention. July 22-25, 2007. Sydney. Abstract WESS104.