4th International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV 22-25 September 2002, San Diego, CA, USA

PROSPECTIVE STUDY OF REGIONAL BODY COMPOSITION IN ANTIRETROVIRAL-NAÏVE SUBJECTS RANDOMIZED TO RECEIVE ZIDOVUDINE+LAMIVUDINE OR DIDANOSINE+STAVUDINE COMBINED WITH NELFINAVIR, EFAVIRENZ, OR BOTH: A5005s, A SUBSTUDY OF ACTG 384

Antiviral Therapy 2002; 7:L27 (abstract 27)

MP Dubé¹, R Zackin², P Tebas³, R Roubenoff⁴, K Mulligan⁵, G Robbins⁶, Y Yang², R Shafer⁷, S Snyder⁸, and SK Grinspoon^6
1Indiana University, Indianapolis, Ind., USA; ²Statistical and Data Analysis Center, Boston, Mass., USA; ³Washington University, St. Louis, Mo., USA; ⁴Tufts University, Boston, Mass., USA; ⁵University of California at San Francisco, San Francisco, Calif., USA; ⁶Harvard University, Boston, Mass., USA; ⁷Stanford University, Palo Alto, Calif., USA; ⁸ACTG Operations Center, Silver Spring, Md., USA

BACKGROUND: The role of different antiretroviral agents in causing body fat changes remains controversial. Cross-sectional and observational studies have been limited by the effects of prior therapies, and the lack of randomization or longitudinal assessments.

METHODS: Antiretroviral-naïve subjects received zidovudine+lamivudine or didanosine+stavudine plus nelfinavir, efavirenz, or both, in a sub-study of a prospective trial. Whole-body dual-energy x-ray absorptiometry (DEXA) scans were obtained at entry and at 16 weeks for 156 subjects and centrally analysed. Statistical analyses were intent-to-treat; all changes are reported as medians. Results up to week 80 are reported.

RESULTS: Baseline characteristics (gender, race/ethnicity, age, BMI, CD4 count and HIV-1 RNA) were similar across treatment groups (zidovudine+lamivudine: n=69; didanosine+stavudine: n=87; nelfinavir: n=47; efavirenz: n=50; nelfinavir+efavirenz: n=59). After initial increases in the first 16-32 weeks, limb (arm+leg) fat decreased progressively in both nucleoside reverse transcriptase inhibitor (NRTI) groups and with efavirenz or nelfinavir. At 48 weeks there were significant differences between the didanosine+stavudine and zidovudine+lamivudine groups in percentage change in limb fat from baseline (-7.5% [-0.28 kg] versus +4.7% [+0.26 kg], respectively; P=0.027, Kruskal-Wallis test); significant differences between these groups also occurred at weeks 64 and 80. At 80 weeks, limb fat decreased 10.7% (-0.50 kg) with efavirenz and 18.0% (-0.92 kg) with nelfinavir (P=0.019). Trunk fat tended to increase after baseline in all groups; no differences occurred between didanosine+stavudine and zidovudine+ lamivudine or efavirenz and nelfinavir groups. Whites (n=80) and non-whites (n=76) experienced similar changes in limb fat. There was a positive correlation between percentage change in limb fat and percent change in trunk fat at weeks 48 and 64 (Spearman r=0.69 and 0.68, respectively). Total bone mineral content and lumbar bone mineral density did not change significantly between groups.

CONCLUSIONS: Antiretroviral-naïve subjects randomized to didanosine+stavudine lost a greater proportion of limb fat than those receiving zidovudine+lamivudine at weeks 48-80. Subjects randomized to nelfinavir lost a greater proportion of limb fat at week 80 than with efavirenz. Although trunk fat increased across all groups, regimen-specific differences in trunk fat changes were not detected. Analysis of metabolic variables and self-perceived body image is needed to evaluate the clinical significance of these findings.

Presenting author: MP Dubé

2002-09-22
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