Paper # 819
Lipid Profiles of TMC278 and EFV in Treatment-naďve HIV-1+ Patients: Pooled Week-48 Data from the Randomized Double-blind Phase III ECHO and THRIVE Trials
Jose Arribas*1, J Andrade-Villanueva2, N Bellos3, P Cahn4, C Katlama5, J Lalezari6, K Ruxrungtham7, D Wohl8, S Vanveggel9, and K Boven10
1Hosp Univ La Paz, Madrid, Spain; 2Hosp Civil de Guadalajara, Univ of Guadalajara, Mexico; 3Southwest Infectious Disease Assoc, Dallas, TX, US; 4Hosp Juan Fernandez and Fndn Huesped, Buenos Aires, Argentina; 5Univ Pierre and Marie Curie Paris 6, Hosp Pitie-Salpetriere, France; 6Quest Clin Res, San Francisco, CA, US; 7HIVNAT Res Collaboration, Thai Red Cross AIDS Res Ctr and Chulalongkorn Univ, Bangkok; 8Univ of North Carolina at Chapel Hill, Ctr for AIDS Res, US; 9Tibotec BVBA, Beerse, Belgium; and 10Tibotec Inc, Titusville, NJ, US
Background: TMC278, an investigational NNRTI, had
non-inferior antiviral efficacy compared to efavirenz (EFV) at week 48 in 2
ongoing double-blind randomized phase 3 trials, ECHO (NCT00540449) and THRIVE
(NCT00543725), in treatment-naive HIV+ adult patients. Here we
compare, in fasted conditions, changes in lipid parameters and abnormalities
with TMC278 vs EFV over 48 weeks using pooled phase 3 data.
Methods: Patients received (1:1) TMC278 25 mg once
daily or EFV 600 mg once daily + tenofovir/emtricitabine (TDF/FTC) (ECHO) or
TDF/FTC, zidovudine/lamivudine (AZT/3TC), or abacavir (ABC)/3TC (THRIVE).
Results: Baseline characteristics (n = 1368): 24%
female, 61% Caucasian, 23% black or African American, and 13% Asian. Background
N(t)RTI: TDF/FTC (80%), AZT/3TC (15%), and ABC/3TC (5%). Treatment to emergent
dyslipidemia did not lead to discontinuation in either group. Significantly
greater increases in total cholesterol (TC), LDL cholesterol (LDLc), and
triglycerides (TG) from baseline to week 48 were seen with EFV than with TMC278
(see the figure). HDL cholesterol (HDLc) increased significantly more with EFV
than with TMC278. There was no difference in the change in the TC/HDLc ratio
between groups (see the figure). The proportions of patients with lipid values
outside National Cholesterol Education Program (NCEP) cut-offs at any time
point during treatment were: TC (TMC278 27% vs EFV 52%, p <0.0001),
LDLc (25% vs 45%, respectively, p <0.0001), HDLc (80% vs 75%), and TG
(47% vs 61%, p <0.0001). TMC278 was compared with EFV using Fisher’s exact
test and post-hoc analyses. The incidence of grade 3/4 lipid-related
abnormalities was lower with TMC278 than with EFV for TC (0.1% vs 3%, p ≤0.001),
LDLc (1% vs 4%, p ≤0.001), and TG (0.3% vs 2% p ≤0.001),
as well as for each lipid parameter by background N[t]RTIs; e.g., TC 0.2% vs 2%
p ≤0.001 (TDF/FTC), 0% vs 3% p ≤0.001 (AZT/3TC), 0% vs
15% p ≤0.001 (ABC/3TC). Lipid-related abnormalities (all grades)
were also lower for TMC278 than for EFV. Use of lipid to lowering drugs on
treatment was low in both groups (TMC278 2% vs EFV 4%). Change from baseline to
week 48 in Framingham Coronary Heart Disease (CHD) relative risk score (10-year
risk) (although this has not been validated in HIV+ patients for LDLc,
it was the same in both groups (–0.09, p ≤0.001).
Conclusions: In the ECHO and THRIVE trials, TMC278
produced minimal change in TC, LDLc, and TG. In contrast, beginning early in
treatment and sustained over 48 weeks, there were significantly greater
increases in these lipid parameters and HDLc and more lipid abnormalities with
EFV. Change from baseline in Framingham CHD risk score was similar in both
groups.
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