Plasma concentrations of the protease inhibitor lopinavir are not associated with elevated blood lipids, according to an Italian study published in the March 1st edition of the Journal of Acquired Immune Deficiency Syndromes.
Investigators from the on-going Resistance and Dosage Adapted Regimens (RADAR) study into therapeutic drug monitoring conducted the study following suggestions that levels of Kaletra in the blood were associated with a risk of serious (grade three) elevations in total triglyceride and cholesterol levels. On the basis of these data it has been suggested that the standard dose of Kaltera should be reduced to help counter lipid increases.
A total of 55 individuals were recruited to the study. The average age was 39 years, 29 (64%) were men, and 29 individuals were also coinfected with hepatitis C virus, and a further two individuals were coinfected with hepatitis B virus. Plasma concentrations of lopinavir were monitored at entry to the study and then at weeks four and twelve.
Mean plasma concentrations of lopinavir were 7.16µ/ml at baseline. 6.73µ/ml at week four, and 6.10µ/ml at week twelve. Triglyceride levels at baseline, weeks four and week twelve were 168mg/dL, 256mg/dL, and 276mg/dL respectively, and the increases in triglyceride levels at week four (p=0.006) and twelve (p=0.005) were significant. The investigators found a mean increase in triglyceride levels of 8.5-mg/dL for each week of follow-up (p=0.014).
However, no significant increase was seen in mean cholesterol levels throughout the period of follow-up.
Adjusting for time, the investigators failed to find any association between plasma concentrations of lopinavir and total triglyceride or cholesterol levels. What’s more, no association was found between an elevation in lopinavir levels of above 8µ/ml and grade three hyperlipidaemia (triglycerides above 750mg/dL and cholesterol above 300mg/dL), even though 40% of patients reached this cut-off concentration of lopinavir.
A total of six patients had grade two hyperlipidaemia (triglycerides above 400mg/dL and cholesterol above 240mg/dL) but none of these instances was related to plasma concentrations of lopinavir.
In a final analysis, the investigators looked at AUC values for lopinavir concentrations and failed to find any significant relationship with either triglyceride (p=0.092) or cholesterol (p=0.49).
”These results may indicate that it is premature to suggest a LPV/r dose reduction based on plasma drug concentrations to prevent or treat abnormal lipid elevations”, conclude the investigators.
Further information on this website
Metabolic changes on HAART - overview
Torti C et al. Lipid abnormalities in HIV-infected patients are not correlated with lopinavir plasma concentrations. JAIDS 35: 324 -326, 2004.