Treatment interruptions improve lipids within four weeks: IL-2 has no metabolic effect
Graham McKerrow, HIV i-Base
An American study was designed to evaluate the effects of IL-2 and treatment interruptions (TI) on lipid and glucose metabolism.
The 47 subjects were randomised to receive or not three 5-day cycles of IL-2, 4.5 million units sc BID every 8 weeks (n=23 and 24 respectively) for 18 weeks. Then, they discontinued ARV treatment until CD4 count dropped below 350 cells/mm3.
Three cycles of IL-2 did not affect lipid or glucose metabolism. After 48 weeks of TI there were significant decreases of triglycerides (from 172 mg/dl, -20%, p < .001), total cholesterol (from 213 mg/dl, -15%, p <.001), HDL cholesterol (from 41 mg/dl, -16%, p < .001) and LDL cholesterol (126 mg/dl, -12%, p=0.008). There were no significant changes in glucose or insulin levels or HOMA-IR (reciprocal index of homeostasis model assessment). Lipid changes occurred relatively early after interruption (within the first 4 weeks).
The researchers concluded that 3 cycles of IL-2 did not have significant metabolic effects on patients receiving stable ARV therapy. However, structured TI is associated with immediate and sustained decreases in cholesterol levels (both LDL and HDL) and triglycerides (TG). The effects on glucose and insulin metabolism were limited in this cohort.
Tebas and colleagues write: “A strategy of intermittent therapy can decrease the cardiovascular risk associated with ARV therapy and provide insight into which of the metabolic abnormalities observed in treated patients are HIV or ARV related.”
Tebas P, Henry K, Cherng D et al. The metabolic effects of intermittent antiretroviral therapy with and without IL-2 (ACTG A5102). 6th Lipodystrophy Workshop (6th IWADRLH), Washington, 2004. Abstract 20. Antiviral Therapy 2004; 9:L13.