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.

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 (n=213) 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; P=.001, 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; P=.05). The median fat-free mass for the entire group increased by 1.2 kg at week 64 (change, +2.0%; P<.001); the increase was greater in the zidovudine-lamivudine group (n=70; change, +1.8 kg) than in the stavudine-didanosine group (n=79; change, +0.5 kg; P=.04), and the increase was also greater for efavirenz recipients (n=53; change, +2.1 kg) than among nelfinavir recipients (n=47; change, +0.4 kg; P=.003). 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.