929
Fasted Lipid Changes after Administration of Maraviroc or Efavirenz in Combination with Zidovudine and Lamivudine for 48 weeks to Treatment-naïve HIV-infected Patients
E DeJesus*1, S Walmsley2, C Cohen3, D Cooper4, B Hirschel5, J Goodrich6, H Valdez7, J Heera6, N Rajicic6, and H Mayer6
1Orlando Immunology Ctr, FL, US; 2Univ of Toronto, Canada; 3Community Res Initiative of New England, Boston, MA, US; 4Univ of New South Wales, Australia; 5Hosp Univ of Geneva, Switzerland; 6Pfizer Global R&D, New London, CT, US; and 7Pfizer Inc, New York, NY, US
Background: Exposure to many of the current agents
typically used as components of HAART are associated with hyperlipidemia, which
adversely affects cardiovascular (CV) risk. The lipid effects of maraviroc (MVC)
and efavirenz (EFV) in treatment-naive patients receiving combinavir (CBV) are presented.
Methods: MERIT is an ongoing, randomized trial
comparing the efficacy and safety of CBV+MVC 300 mg twice daily or EFV 600 mg once
daily in treatment-naive patients infected with only R5 HIV, by the Trofile®
assay. Fasting serum lipids were measured at the baseline, and weeks 24 and 48
visits or at early termination. Median maximum changes (mg/dL) in total
cholesterol (TC), HDL cholesterol (HDL), triglycerides (TG), calculated LDL cholesterol (LDL), and TC-to-HDL ratio (TC:HDL) and the proportion of patients exceeding
borderline high 2001 NCEP thresholds are compared between groups.
Results: 721 patients were randomized and received at
least one dose of medication in the MVC+CBV (360) and EFV+CBV (361) groups. Baseline
lipid values and the % of patients exceeding National Cholesterol Education
Program (NCEP) thresholds at baseline were comparable between groups.
Median maximum change from baseline in TC, HDL, TG, and LDL were greater in the
EFV group as compared with the MVC group, whereas median decrease in TC:HDL was greater in the MVC group (p <0.01). The percentage of patients exceeding NCEP
thresholds at baseline were not different, but were highly statistically
different on therapy for TC and LDL (p <0.0001) favoring MVC+CBV.
|
|
Median baseline
mg/dL
(25th,75th centile)
|
Median maximum change from baseline
mg/dL
(25th,75th centile)
|
Percentage patients above NCEP threshold at baseline
|
Percentage patients with study emergent values above
NCEP threshold
|
|
|
MVC
|
EFV
|
MVC
|
EFV
|
MVC
|
EFV
|
MVC
|
EFV
|
|
TC
|
156
(131,181)
|
156
(131, 178)
|
+6
(–20, 23)
|
+33**
(17, 55)
|
7
|
6
|
5
|
18**
|
|
HDL
|
37
(31, 46)
|
38
(32, 46)
|
+7
(–1, 13)
|
+13**
(7, 20)
|
—
|
—
|
—
|
—
|
|
LDL
|
92
(71, 114)
|
88
(70, 111)
|
–9
(–24, 13)
|
+20**
(–2, 37)
|
6
|
4
|
3
|
12**
|
|
TC:HDL
|
4.2
(3, 5)
|
4.0
(3, 5)
|
–0.5
(–1, 0.2)
|
–0.4*
(–1, 0.5)
|
—
|
—
|
—
|
—
|
|
TG
|
106
(76, 154)
|
104
(73, 162)
|
–9
(–45, 43)
|
+20**
(–23, 69)
|
7
|
7
|
7
|
8
|
NCEP threshold values: TC >199 mg/dL (>5.1 mM); LDL >129 mg/dL (>3.3 mM); TG >199 mg/dL (>2.2 mM)
*p <0.01; **p <0.001
Conclusions: Median maximum lipid increases (TC, HDL, LDL, and TG) were greater for patients on EFV+CBV. TC:HDL decreased more in patients on MVC+CBV
while the percentage of patients with TC and LDL >NCEP guidelines was higher
in the EFV+CBV vs MVC+CBV group. These data demonstrate that MVC has minimal effect on lipid profiles and is at least as lipid neutral as EFV.
|
