Effects of Potent Antiretroviral Therapy on Free Testosterone Levels and Fat‐Free Mass in Men in a Prospective, Randomized Trial: A5005s, a Substudy of AIDS Clinical Trials Group Study 384
1Division of Infectious Diseases, Indiana University, Indianapolis; 2Statistical and Data Analysis Center, Harvard School of Public Health, and Divisions of 3Infectious Diseases and 4Endocrinology, Harvard Medical School, and 5Friedman School of Nutrition Science and Policy, Tufts University, Boston, Massachusetts; 6Division of Endocrinology, University of California at San Francisco; and 7Division of Infectious Diseases, University of Pennsylvania, Philadelphia
Background.
Low testosterone levels are commonly reported in patients with advanced human immunodeficiency virus disease. The effects of initiation of different antiretroviral regimens on testosterone levels and changes in fat‐free mass have not been reported.
Methods.Antiretroviral‐naive men (
) were randomized to receive nelfinavir, efavirenz, or both plus either zidovudine and lamivudine or stavudine and didanosine. Patients underwent measurements of metabolic parameters, including determination of free testosterone level by equilibrium dialysis and bioelectrical impedance analysis, over a 64‐week period.
Results.At baseline, the median free testosterone level was 92 pg/mL; the level was subnormal (i.e., <50 pg/mL) in 6%. Lower CD4 cell count at the time of study entry, higher weight, and greater age were independently associated with lower baseline free testosterone level. At week 64, the median free testosterone level increased more in zidovudine‐lamivudine recipients (48 of whom had paired values available; change, +31 pg/mL) than in stavudine‐didanosine recipients (57 of whom had paired values; change, +3 pg/mL; 
, by Wilcoxon rank sum test), and it increased more in efavirenz recipients (37 of whom had paired values; change, +30 pg/mL) than in nelfinavir recipients (28 of whom had paired values; change, −3 pg/mL; 
). The median fat‐free mass for the entire group increased by 1.2 kg at week 64 (change, +2.0%; 
); the increase was greater in the zidovudine‐lamivudine group (
; change, +1.8 kg) than in the stavudine‐didanosine group (
; change, +0.5 kg; 
), and the increase was also greater for efavirenz recipients (
; change, +2.1 kg) than among nelfinavir recipients (
; change, +0.4 kg; 
). White race, lower CD4 cell count at study entry, assignment to the efavirenz treatment arm, and assignment to the zidovudine‐lamivudine treatment arm independently predicted greater absolute change in fat‐free mass at week 64.
Conclusions.Subnormal free testosterone levels occurred infrequently among these antiretroviral‐naive men. Free testosterone and fat‐free mass levels increased after initiation of antiretroviral therapy, with greater increases at 64 weeks among zidovudine‐lamivudine recipients than among stavudine‐didanosine recipients and among efavirenz recipients than among nelfinavir recipients.
Received 23 January 2007; accepted 22 March 2007; electronically published 22 May 2007.
Cited by
Online publication date: 1-Dec-2007.
Online publication date: 1-Dec-2007.
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Presented in part: XVI International AIDS Conference, 13–18 August 2006, Toronto, Canada (abstract THPE 0121).
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Present affiliation: Amgen, Thousand Oaks, California.
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Members of the study group are listed at the end of the text.