Treatment interruption results in lipid reduction; IL-2 has no effect on lipids

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A structured treatment interruption in patients with moderately elevated lipid levels resulted in lipid reductions of 15 to 20% that were sustained for over one year off treatment, according to findings presented to the Sixth International Workshop on Lipodystrophy and Adverse Drug Reactions in HIV this week in Washington DC, USA.

Dr Pablo Tebas of the University of Pennsylvania reported on ACTG A5102, a study of the metabolic effects of CD4-guided treatment interruption.

The study recruited 47 patients, half of whom were taking non-nucleoside reverse transcriptase inhibitor (NNRTI)-containing regimens. The other half was taking protease inhibitor-containing regimens, predominantly including nelfinavir (Viracept).

Glossary

treatment interruption

Taking a planned break from HIV treatment, sometimes known as a ‘drugs holiday’. As this has been shown to lead to worse outcomes, treatment interruptions are not recommended. 

lipid

Fat or fat-like substances found in the blood and body tissues. Lipids serve as building blocks for cells and as a source of energy for the body. Cholesterol and triglycerides are types of lipids.

cholesterol

A waxy substance, mostly made by the body and used to produce steroid hormones. High levels can be associated with atherosclerosis. There are two main types of cholesterol: low-density lipoprotein (LDL) or ‘bad’ cholesterol (which may put people at risk for heart disease and other serious conditions), and high-density lipoprotein (HDL) or ‘good’ cholesterol (which helps get rid of LDL).

triglycerides

A blood fat (lipid). High levels are associated with atherosclerosis and are a risk factor for heart disease.

 

metabolism

The physical and chemical reactions that produce energy for the body. Metabolism also refers to the breakdown of drugs or other substances within the body, which may occur during digestion or elimination.

Participants in the study were randomised to receive three five-day cycles of interleukin-2 (IL-2; 4.5 million IU twice daily) six weeks apart or no intervention prior to CD4-guided treatment interruption. Treatment was resumed if the CD4 cell count fell below 350 cells/mm3, and participants in the IL-2 group then received 24 weeks of antiretroviral treatment before three further cycles of IL-2. Treatment would be stopped again after this point if the CD4 cell count had risen above 500 cells/mm3.

Three five-day cycles of IL-2 treatment six weeks apart resulted in no elevations in glucose, insulin, triglycerides or cholesterol.

After treatment interruption no patients resumed treatment during a median follow-up of 56 weeks. However, significant reductions in levels of triglycerides, total cholesterol and low density lipoprotein (LDL) cholesterol were observed. Triglycerides fell by 20% from 178 mg/dl (p

Commenting on his findings, Dr Tebas suggested that treatment interruption may prove a viable option for management of lipid elevations in patients at lower risk of disease progression during a treatment interruption. However, the strategy is unlikely to be appropriate for people who started treatment with a low CD4 cell count, since a number of studies have now shown that treatment interruption in this group of patients tends to result in a rapid return of the CD4 cell count to the pre-treatment level.

References

Tebas P et al. The metabolic effects of intermittent antiretroviral therapy with and without IL-2 (ACTG A5102). Antiviral Therapy 9: L13, 2004.