Mixed Patterns of Changes in Central and Peripheral Fat Following Initiation of Antiretroviral Therapy in a Randomized Trial

Mulligan, Kathleen PhD*; Parker, Robert A. ScD†; Komarow, Lauren MS†; Grinspoon, Steven K. MD‡; Tebas, Pablo MD§; Robbins, Gregory K. MD‡; Roubenoff, Ronenn MD, MHS∥; Dubé, Michael P. MD¶; for the ACTG 384 and A5005s Study Teams

JAIDS Journal of Acquired Immune Deficiency Syndromes: 15 April 2006 - Volume 41 - Issue 5 - pp 590-597
doi: 10.1097/01.qai.0000214811.72916.67
Clinical Science

Introduction: Although peripheral fat loss is a consistent feature of HIV-associated lipodystrophy, less is known about whether changes in central and peripheral fat occur in tandem or independently over time. We examined intraindividual changes in dual-energy x-ray absorptiometry (DEXA) and anthropometry data over 64 weeks after initiation of antiretroviral therapy (ART).

Methods: In ACTG 384, ART-naive subjects were randomized to receive didanosine and stavudine or zidovudine and lamivudine plus efavirenz, nelfinavir, or both. In the metabolic substudy A5005S (N'= 329), waist, hip, thigh, and arm circumferences were measured in triplicate. DEXA scanning was performed in 157 subjects.

Results: Individual changes in limb and trunk fat at week 64 correlated positively (R =.72, P <.001). Most subjects had directionally concordant changes in limb and trunk fat (36% gained and 32% lost in both regions). In 26%, trunk fat increased while limb fat decreased, whereas the reverse occurred in only 6% (P <.001). Changes in waist and hip circumferences also correlated positively (R =.62, P <.001). The proportion of subjects with waist/hip ratio more than.95 (men) or.90 (women) was 34% at baseline and 47% at week 64 (P =.003). In those who developed increased waist/hip ratio, 76% had increased waist circumference.

Conclusions: Individual results obtained by both anthropometry and DEXA show diverse patterns of fat gain and loss over 64 weeks after initiation of ART, but changes tended to occur in the same direction. Increased waist/hip ratio was predominantly associated with increased waist circumference. There was no evidence that central fat accumulation and peripheral fat loss are linked in most subjects.

From the *Department of Medicine, Division of Endocrinology, San Francisco General Hospital, University of California at San Francisco, San Francisco, CA; †Statistical and Data Analysis Center, Harvard University, Boston, MA; ‡Massachusetts General Hospital, Harvard University, Boston, MA; §University of Pennsylvania, Philadelphia, PA; ∥Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA; and ¶Indiana University, Indianapolis, IN.

Received for publication October 2, 2005; accepted January 18, 2006.

Supported by grants to the AIDS Clinical Trials Group from the National Institute of Allergy and Infectious Diseases (AI38855 and AI38858). The parent protocol (ACTG 384) was supported in part by Agouron Pharmaceuticals, Inc., Bristol-Myers Squibb Company, DuPont Pharmaceutical Company, GlaxoSmithKline, Inc., and Merck and Co., Inc.

These data were presented in part at the 12th Conference on Retroviruses and Opportunistic Infections, February 2005, Boston, MA.

Reprints: Michael P. Dubé, MD, Wishard Memorial Hospital, 1001 W. 10th Street, Suite OPW-430, Indianapolis, IN 46202 (e-mail: mpdube@iupui.edu).

© 2006 Lippincott Williams & Wilkins, Inc.