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Background:  Switching to drugs with less mitochondrial toxicity or reducing stavudine (d4T) dose may be of benefit in HIV-infected patients receiving antiretroviral therapy containing d4T, but the efficacy and the safety of these strategies is unknown.

Methods:  Clinically stable HIV-infected patients receiving antiretroviral therapy containing 40 mg d4T twice daily with a plasma HIV RNA < 200 copies/mL for at least the previous 6 months were randomized to maintain (40 mg twice daily) (d4T40 group) or to reduce (30 mg twice daily) (d4T30 group) d4T or to switch from d4T to tenofovir (TDF group) while preserving the remaining drugs unchanged. Fasting plasma glucose, triglycerides, lactate, and total-, HDL-, and LDL-cholesterol were assessed at baseline and 1, 3, and 6 months. Mitochondrial oxidative activity (polarography) and body fat (DXA) were assessed at baseline and 6 months.

Results:  There were 56 patients (96% men):  d4T40 (n = 20), d4T30 (n = 18), and TDF (n = 18). Median (IQR) time on d4T had been 5 (3 to 8) years. Median age was 42 (IQR 39 to 49) years. Median CD4 cells were 612/mm³ (IQR 388 to 848). Median values of metabolic parameters were: glucose 87 (IQR 81 to 95), triglycerides 172 (120 to 262), total cholesterol 222 (203 to 252), LDL-cholesterol 141 (126 to 155), HDL-cholesterol 47 (42 to 54), and lactate 14 (11 to 16) mg/dL. One patient in the d4T40 group discontinued the study due to symptomatic hyperlactatemia. At 6 months, all patients but 1 (d4T40 group) had a plasma HIV RNA < 200 copies/mL. Significant changes in laboratory parameters, including mitochondrial function, were only detected in triglycerides (mean, mg/dL) (+19, d4T40; –40, d4T30; –133, TDF; p = 0.02) and total cholesterol (mean, mg/dL) (+4, d4T40; –4, d4T30; –28, TDF; p = 0.04). Mean changes in total (–597, d4T40; +332, d4T30; +1005, TDF; p = 0.04) and limb fat (–247, d4T40; +77, d4T30; +440, TDF; p = 0.008) (gr) significantly differed among groups.

Conclusions:  Reducing d4T dose from 40 to 30 mg twice was as effective as switching from d4T to TDF in HIV-infected patients receiving antiretroviral therapy containing d4T. Both strategies were associated with decreases in plasma lipids and increases in body fat, although the effect of switching to TDF was higher than that of reducing d4T dose.

Keywords: stavudine; dose reduction; switch