Share this article on:

Glucose metabolism, lipid, and body fat changes in antiretroviral-naive subjects randomized to nelfinavir or efavirenz plus dual nucleosides

Dubé, Michael Pa; Parker, Robert Ab; Tebas, Pablof; Grinspoon, Steven Kc; Zackin, Robert Ab,*; Robbins, Gregory Kd; Roubenoff, Ronenne; Shafer, Robert Wg; Wininger, David Ah; Meyer, William A IIIi; Snyder, Sally Wj; Mulligan, Kathleenk

doi: 10.1097/
Clinical Science

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.

From the aDivision of Infectious Diseases, Indiana University, Indianapolis, Indiana

bStatistical and Data Analysis Center, Harvard School of Public Health

cDivision of Nutrition

dDivision of Infectious Diseases, Harvard University

eFriedman School of Nutrition Science and Policy, Tufts University, Boston, Massachusetts

fDivision of Infectious Diseases, University of Pennsylvania, Philadelphia, Pennsylvania

gDivision of Infectious Diseases, Stanford University, Palo Alto, California

hDivision of Infectious Diseases, Ohio State University, Columbus, Ohio

iQuest Diagnostics Incorporated, Baltimore

jSocial & Scientific Systems Inc, Silver Spring, Maryland

kDivision of Endocrinology, University of California at San Francisco, San Francisco, California, USA.

* Deceased.

Received 18 January, 2005

Revised 20 March, 2005

Accepted 5 April, 2005

Correspondence to Dr M.P. Dubé, Wishard Memorial Hospital, 1001 W 10th St, Suite OPW-430, Indianapolis, IN 46202, USA. Email:

© 2005 Lippincott Williams & Wilkins, Inc.