Lipoprotein changes in HIV-infected antiretroviral-naïve individuals after starting antiretroviral therapy: ACTG Study A5152s

Stein, James H.; Komarow, Lauren; Cotter, Bruno R.; Currier, Judith S.; Dubé, Michael P.; Fichtenbaum, Carl J.; Gerschenson, Mariana; Mitchell, Carol K.C.; Murphy, Robert L.; Squires, Kathleen; Parker, Robert A.; Torriani, Francesca J.; ACTG 5152s Study Team,

doi:10.1016/j.jacl.2008.08.442

« Previous Next »Journal of Clinical Lipidology
Volume 2, Issue 6 , Pages 464-471, December 2008

Lipoprotein changes in HIV-infected antiretroviral-naïve individuals after starting antiretroviral therapy: ACTG Study A5152s

James H. Stein, MD, FAHA
- University of Wisconsin School of Medicine and Public Health, 600 Highland Avenue, G7/341 CSC (MC 3248), Madison, WI 53792, USA
- Corresponding author
Lauren Komarow, MS
- Harvard School of Public Health, Boston, MA, USA
Bruno R. Cotter, MD
- University of California-San Diego, San Diego, CA, USA
Judith S. Currier, MD
- University of California-Los Angeles, Los Angeles, CA, USA
Michael P. Dubé, MD
- Indiana University School of Medicine, Indianapolis, IN, USA
Carl J. Fichtenbaum, MD
- University of Cincinnati Medical Center, Cincinnati, OH, USA
Mariana Gerschenson, PhD
- University of Hawaii, Honolulu, HI, USA
Carol K.C. Mitchell, PhD
- University of Wisconsin School of Medicine and Public Health, 600 Highland Avenue, G7/341 CSC (MC 3248), Madison, WI 53792, USA
Robert L. Murphy, MD
- Northwestern University, Feinberg School of Medicine, Chicago, IL, USA
Kathleen Squires, MD
- University of Southern California, Los Angeles, CA, USA
Robert A. Parker, ScD
- Harvard School of Public Health, Boston, MA, USA
Francesca J. Torriani, MD
- University of California-San Diego, San Diego, CA, USA
ACTG 5152s Study Team

Received 3 June 2008; accepted 16 August 2008. published online 22 August 2008.

Background

Dyslipidemia is a frequent complication of antiretroviral therapy (ART) for patients with human immunodeficiency virus infection (HIV). The effects of ART on lipoproteins are less well-understood, and have not been investigated in a prospective study where assignment to ART is randomized.

Objective

To evaluate the effects of three class-sparing ART regimens on lipids and lipoproteins.

Methods

This was a substudy of a prospective, multicenter study of treatment-naïve HIV-infected individuals randomly assigned to receive a regimen of nucleoside reverse transcriptase inhibitors (NRTIs) + the non-nucleoside reverse transcriptase inhibitor efavirenz, NRTIs + the protease inhibitor lopinavir/ritonavir, or a NRTI-sparing regimen of efavirenz + lopinavir/ritonavir. Lipoproteins were measured by nuclear magnetic resonance spectroscopy.

Results

Among the 82 participants, total and small low-density lipoprotein concentrations increased by a median of 152 nmol/L (interquartile range, −49 to +407 nmol/L; P < 0.01) and 130 nmol/L (interquartile range, −98 to +417 nmol/L; P < 0.01), respectively, especially in the arms containing lopinavir/ritonavir (P_KW < 0.04). Very-low-density lipoproteins also increased (P < 0.01), with a larger increase in the arms that contained lopinavir/ritonavir (P = 0.022). High-density lipoproteins increased by a median of 6.0 nmol/L (interquartile range, 2.8–10.4 nmol/L; P < 0.01), but differences between arms were not significant (P_KW = 0.069). Changes were not related to changes in markers of insulin/glucose metabolism.

Conclusions

Total and small low-density lipoprotein concentrations increased, especially in the arms containing lopinavir/ritonavir, as did increases in total very-low-density lipoproteins. Adverse changes were especially prominent in the arm with efavirenz + lopinavir/ritonavir.

Keywords: Antiretroviral therapy, Cardiovascular risk, Clinical trial, Human immunodeficiency virus, Lipids, Lipoproteins