Lipid profiles for etravirine versus efavirenz in treatment-naive patients in the randomized, double-blind SENSE trial.
BACKGROUND
Etravirine is approved for use in treatment-experienced patients at a dose of 200 mg twice daily. Efavirenz has been associated with greater increases in serum lipids compared with other non-nucleosides in randomized trials of first-line treatment.


METHODS
In this double-blind, placebo-controlled trial, 157 treatment-naive patients with HIV RNA >5000 copies/mL were randomized 1:1 to either 400 mg of etravirine once daily (n=79) or 600 mg of efavirenz once daily (n=78) plus two nucleoside analogues (either abacavir/lamivudine, zidovudine/lamivudine or tenofovir/emtricitabine) for 48 weeks. Lipids were measured under fasting conditions at baseline and all visits to Week 48. Clinicaltrials.gov identifier: NCT00903682.


RESULTS
Overall, the patients had a median baseline CD4 count of 302 cells/mm(3) (range 74-722) and a median HIV RNA of 4.8 log(10) copies/mL (range 3.5-6.6). Both the non-nucleosides and the nucleoside analogues used caused changes in serum lipids. In the efavirenz arm, patients showed significantly larger increases in high-density lipoprotein (HDL) (+0.15 mmol/L, P=0.004), low-density lipoprotein (LDL) (+0.35 mmol/L, P=0.005), total cholesterol (+0.61 mmol/L, P<0.0001) and triglycerides (+0.33 mmol/L, P=0.03) at Week 48 compared with the etravirine arm. Across the two arms, patients taking abacavir/lamivudine showed greater increases in total cholesterol (+0.47 mmol/L, P=0.005) compared with patients taking tenofovir/emtricitabine. There were fewer grade 3/4 elevations in total cholesterol, LDL and triglycerides in the etravirine arm (2 patients, 1 patient and 0 patients, respectively) versus the efavirenz arm (8 patients, 6 patients and 2 patients, respectively).


CONCLUSIONS
In the SENSE trial, first-line treatment with 400 mg of etravirine once daily plus two nucleoside analogues led to fewer grade 3 or 4 lipid elevations compared with efavirenz plus two nucleoside analogues.
First Department of Internal Medicine, University Hospital of Cologne, Cologne, Germany. g.faetkenheuer@uni-koeln.de
G
G
Fätkenheuer
C
C
Duvivier
A
A
Rieger
J
J
Durant
D
D
Rey
W
W
Schmidt
A
A
Hill
Y
Y
van Delft
S
S
Marks
D000293:Adolescent; D000328:Adult; D000368:Aged; D000480:Alkynes; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000009:adverse effects; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects / Q000379:methods*; D048588:Benzoxazines / Q000008:administration & dosage* / Q000009:adverse effects; D003521:Cyclopropanes; D004311:Double-Blind Method; D005260:Female; D006678:HIV / Q000302:isolation & purification; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D008055:Lipids / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009570:Nitriles; D010919:Placebos / Q000008:administration & dosage; D011724:Pyridazines / Q000008:administration & dosage* / Q000009:adverse effects; D011743:Pyrimidines; D019562:Viral Load; D055815:Young Adult
D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D008055:Lipids; D009570:Nitriles; D010919:Placebos; D011724:Pyridazines; D011743:Pyrimidines; C451734:etravirine; C098320:efavirenz