Metabolic effects of protease inhibitor-sparing antiretroviral regimens given as initial treatment of HIV-1 Infection (AIDS Clinical Trials Group Study A5095).
OBJECTIVE
To assess metabolic changes after initiation of protease inhibitor (PI)-sparing regimens in antiretroviral-naive patients.


METHODS
Metabolic changes were analyzed within the triple-nucleoside (zidovudine [ZDV]/lamivudine [3TC]/abacavir [ABC])-containing, 3-drug efavirenz (EFV) [ZDV/3TC + EFV]-containing, and 4-drug EFV [ZDV/3TC/ABC + EFV]-containing arms of the AIDS Clinical Trials Group multicenter trial A5095. Metabolic values were compared with published US general population norms.


RESULTS
From week 0 to week 24, all arms exhibited similar mild median increases in glucose and decreases in insulin sensitivity, whereas changes in lipids were greater in the ZDV/3TC + EFV and ZDV/3TC/ABC + EFV arms than in the ZDV/3TC/ABC arm: triglyceride (TG; 7, 18, and -1 mg/dL, respectively), total cholesterol (TC; 23, 28, and 5 mg/dL, respectively), low-density lipoprotein cholesterol (LDL-C; 9, 14, and 1 mg/dL, respectively), and high-density lipoprotein cholesterol (HDL-C; 10, 10, and 5 mg/dL, respectively). Adjusted mean study lipid values of all study participants at week 0 and week 96 compared with those of the National Health and Nutrition Examination Survey (NHANES) 1999 through 2002 values were: TG (148, 187, and 123 mg/dL, respectively), TC (164, 195, and 203 mg/dL, respectively), HDL-C (35, 47, and 51 mg/dL, respectively), and LDL-C (101, 117, and 123 mg/dL, respectively) (P < or = 0.005 for each value vs. NHANES values).


CONCLUSIONS
Similar mild increases in glucose and decreases in insulin sensitivity were observed in all regimens, whereas lipids were modestly higher in the EFV-containing arms. Compared with general population norms, the metabolic dysfunctions of concern after these PI-sparing therapies were increasingly abnormal TC and lower (but improved relative to baseline) HDL-C levels.
Shikuma
Cecilia M
CM
Hawaii AIDS Clinical Research Program, John A. Burns School of Medicine, University of Hawaii at Manoa, Manoa Leihi Hospital, 3675 Kilauea Avenue, Honolulu, HI 96816, USA. shikuma@hawaii.edu
Yang
Yang
Y
Glesby
Marshall J
MJ
Meyer
William A
WA
Tashima
Karen T
KT
Ribaudo
Heather J
HJ
Webb
Nancy
N
Bastow
Barbara
B
Kuritzkes
Daniel R
DR
Gulick
Roy M
RM
D000328:Adult; D000480:Alkynes; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D048588:Benzoxazines / Q000008:administration & dosage; D001786:Blood Glucose / Q000378:metabolism; D001823:Body Composition / Q000187:drug effects; D003521:Cyclopropanes; D015224:Dideoxynucleosides / Q000008:administration & dosage; D004311:Double-Blind Method; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D015497:HIV-1; D006801:Humans; D007333:Insulin Resistance; D019344:Lactic Acid / Q000097:blood; D019259:Lamivudine / Q000008:administration & dosage; D008055:Lipids / Q000097:blood; D008297:Male; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage; D015215:Zidovudine / Q000008:administration & dosage; D000099227:Abacavir
D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D001786:Blood Glucose; D003521:Cyclopropanes; D015224:Dideoxynucleosides; D019344:Lactic Acid; D019259:Lamivudine; D008055:Lipids; D018894:Reverse Transcriptase Inhibitors; D015215:Zidovudine; D000099227:Abacavir; C098320:efavirenz