title: Glucose metabolism, lipid, and body fat changes in antiretroviral-naive subjects randomized to nelfinavir or efavirenz plus dual nucleosides.
abstract: OBJECTIVE
  To determine if particular components of antiretroviral drug regimens are associated with greater insulin resistance, dyslipidemia, and peripheral lipoatrophy.
  
  
  METHODS
  Metabolic and body composition variables were measured prospectively over 64 weeks in 334 antiretroviral-naive, HIV-infected subjects who were randomized to receive nelfinavir, efavirenz, or both, combined with zidovudine/lamivudine or didanosine/stavudine in a factorial design, multicenter trial. Subjects assigned to efavirenz (n = 110) were compared with those assigned to nelfinavir (n = 99); subjects assigned to zidovudine/lamivudine (n = 154) were compared with those assigned to didanosine/stavudine (n = 180). A subset of 157 subjects had serial dual-energy X-ray absorptiometry (DEXA) scans.
  
  
  RESULTS
  Lipid measures increased in all groups. Greater increases in high density lipoprotein (HDL) cholesterol occurred with efavirenz than with nelfinavir. Greater increases in total cholesterol, non-HDL cholesterol and HDL cholesterol occurred with stavudine and didanosine than with zidovudine/lamivudine. There were no differences in insulin resistance in the comparisons. After initial increases in the first 16 weeks, median limb fat decreased. Greater changes in percentage changes in limb fat occurred with didanosine/stavudine (-16.8%) than with zidovudine/lamivudine (+4.0%; P < 0.001 for overall change from baseline) and with nelfinavir (-13.1%) compared with efavirenz (+1.8%; P = 0.003).
  
  
  CONCLUSIONS
  Over 64 weeks, all regimens were associated with increases in lipids but insulin resistance did not differ between groups. Regimens containing didanosine/stavudine and regimens containing nelfinavir were associated with greater loss of limb fat.
authors.affiliation: Division of Infectious Diseases, Indiana University, Indianapolis, Indiana, USA. mpdube@iupui.edu
authors.forename: Michael P
authors.initials: MP
authors.lastname: Dubé
authors.forename: Robert A
authors.initials: RA
authors.lastname: Parker
authors.forename: Pablo
authors.initials: P
authors.lastname: Tebas
authors.forename: Steven K
authors.initials: SK
authors.lastname: Grinspoon
authors.forename: Robert A
authors.initials: RA
authors.lastname: Zackin
authors.forename: Gregory K
authors.initials: GK
authors.lastname: Robbins
authors.forename: Ronenn
authors.initials: R
authors.lastname: Roubenoff
authors.forename: Robert W
authors.initials: RW
authors.lastname: Shafer
authors.forename: David A
authors.initials: DA
authors.lastname: Wininger
authors.forename: William A
authors.initials: WA
authors.lastname: Meyer
authors.forename: Sally W
authors.initials: SW
authors.lastname: Snyder
authors.forename: Kathleen
authors.initials: K
authors.lastname: Mulligan
mesh_terms: D015502:Absorptiometry, Photon; D000273:Adipose Tissue / Q000378:metabolism; D000328:Adult; D000480:Alkynes; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D048588:Benzoxazines; D001786:Blood Glucose / Q000378:metabolism*; D003521:Cyclopropanes; D004359:Drug Therapy, Combination; D050171:Dyslipidemias / Q000139:chemically induced; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D039682:HIV-Associated Lipodystrophy Syndrome / Q000139:chemically induced; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology; D008055:Lipids; D008297:Male; D019888:Nelfinavir / Q000627:therapeutic use*; D009705:Nucleosides / Q000627:therapeutic use*; D010078:Oxazines / Q000627:therapeutic use*
chemical_list: D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D001786:Blood Glucose; D003521:Cyclopropanes; D008055:Lipids; D009705:Nucleosides; D010078:Oxazines; D019888:Nelfinavir; C098320:efavirenz