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Lipid Analysis in Efavirenz & Nelfinavir Regimens
Reported by Jules Levin
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Two different studies were reported at the Lipodystrophy Workshop and at ICAAC comparing the lipid profiles of patients on efavirenz or nelfinavir. Patients in both studies received either a nelfinavir or efavirenz regimen, and researchers compared the changes in lipids. But the study presented at the Workshop also looked at the HDL subclasses, large particle size and small particle size HDL; the authors said an increase in large particle size HDL can be protective in decreasing risk for coronary artery disease and increases in small particle size HDL can increase risk for coronary artery disease.
I'll discuss the Lipodystrophy Workshop study first. There was much in the way of test tube (in vitro) studies at the Workshop trying to decipher the causes of metabolic abnormalities and body changes, and there appears to be increased understanding from these studies; and there were a few clinically relevant studies. You can read the NATAP reports from this Workshop at:
www.natap.org/2002/lipoWorkshop/ndxLipo.htm
A research group from George Washington University (Simon, abstract 14) reported on a more in depth look at lipid changes for patients on efavirenz or nelfinavir regimens with 2 nukes. In the nelfinavir group, total cholesterol rose by 34%, triglycerides by 26%, LDL (bad cholesterol) by 45% and HDL (good cholesterol) by 35%. Among efavirenz recipients total cholesterol rose by 22%, triglycerides by 38%, LDL by 17%, and HDL by 45%. So, LDL increased more in the NFV patients and HDL increased by more in the EFV patients. In each case the increases from baseline were significant. There was no statistically significant difference in cholesterol and triglycerides between patients receiving EFV or NFV. But the difference for both HDL and LDL were significant (p<0.05). The authors said that the subclass analysis revealed an even more striking difference. The authors report -- among the HDL subclasses, large particle HDL is associated with a decreased coronary artery risk whereas small particle HDL is associated with an increased risk. Among NFV recipients, large HDL rose by 8.2% whereas small HDL rose by 44%. In contrast, in the EFV group large HDL rose by 41% (p<0.05 compared to NFV group) and small HDL by 25%. For LDL the main difference between the 2 groups was the number of LDL particles which increased by 45% in the NFV group and 11% in the EFV group (p<0.05). Based on the subclass analysis diffeences, the author suggested that there may be an increased risk for heart disease for patients taking NFV than EFV.
The ICAAC study (Haubrich, abstract H-1914) preliminarily analyzed 162 treatment naive patients after being on therapy for 24 weeks. The study is ongoing and randomized and patients also received Combivir. A further analysis after patients are on therapy for 48 weeks or longer would be informative.
Total cholesterol increased about the same in both groups from baseline to week 24. Mean total cholesterol was 166 mg/dl in nelfinavir (NFV) patients and 161 mg/dl in efavirenz (EFV) patients before starting therapy. After 24 weeks of therapy cholesterol was on average 201 in the NFV patients for an increase of 35, and cholesterol was 195 in the EFV patients for an increase of 34.
Triglycerides also increased about the same in both groups. For NFV baseline TG was 146 mg/dl and 177 mg/dl at week 24 for an increase of 31. In the EFV patients baseline TG was 154 and increased to 196 after 24 weeks, for an increase of 42.
HDL (the good cholesterol) significantly increased (p=0.02) more in the EFV patients. In EFV patients HDL increased by 10 mg/dl from baseline to week 24 (from 40 to 50) and HDL increased 5 mg/dL for NFV patients from baseline to week 24 (from 39 to 44). HDL less than 35 is not looked on favorably and HDL over 40 is good, although a high HDL >60 is considered a negative risk factor for heart disease.
LDL cholesterol (the bad cholesterol) increased significantly more (p=0.04) in the NFV patients. LDL was on average 97 mg/dl in the NFV patients at baseline and increased by 23; EFV patients increased from 94 mg/dl at baseline by 12. Many risk factors are considered in estimating a person's risk for heart disease in addition to cholesterol and triglyceride levels including smoking, diet, exercise, diabetes, high blood pressure, family history, and estrogen replacement for women post menopausal.
The National Cholesterol Education Program Guidelines recommend that treatment and intervention decisions be based on the calculated level of LDL. For patients with an elevated LDL >159 mg/dL (>4.13 mmol/L) who have fewer than 2 risk factors in addition to an elevated LDL and who do not have evidence of atherosclerotic disease, the goal of treatment is an LDL level <160. For those who have at least 2 other risk factors, the goal of treatment is an LDL level <130 (3.37 mmol/L). When LDL levels remain >160 mg/dL despite dietary measures and the patient has 2 or more risk factors (in addition to high LDL), or when LDL remains >190 (>4.92 mmol/L) even without risk factors, the addition of drug treatment should be considered. Bear in mind that there is some controversy about applying these rules in HIV-infected patients, because perhaps elevations in these measures may not have the same impact as in HIV negative individuals. Several studies show increased risk for heart disease in HIV+ individuals, but well designed large studies are probably needed to accurately answer this question. However, if an HIV-infected individual has these abnormalities in lipids doctors are addressing the situation as if the risks are the same as in HIV negative individuals. For those with coronary artery disease, peripheral vascular disease, or cerebrovascular disease, the goal of treatment is an LDL <100 (<2.59 mmol/L). It is uncertain if triglycerides are independent risk factors for heart disease. Like cholesterol, they vary with age. A triglyceride level <200 mg/dL (<2.26 mmol/L) is considered normal, 200 to 400 (2.26 to 4.52 mmol/L) is borderline high, and >400 (>4.52 mmol/L) is high. Hypertriglyceridemia has been associated with diabetes, hyperuricemia (uric acid), and pancreatitis (when levels are >600 mg/dL; >6.78 mmol/L.
The percentage of patients developing LDL cholesterol >160 mg/dL at week 24 was 16% in the NFV groups and 8% in the EFV group, but the difference was not significant in this preliminary week 24 analysis. The percent of patients with >130 mg/dL of LDL cholesterol was 42% in the NFV group and 26% in the EFV group, and the difference at the time of this 24-week analysis was significant (p=0.04).
Triglycerides increased 18 mg/dL from 146 at baseline to 164 at week 24 for NFV patients, and 38 mg/dL from 154 at baseline to 192 at week 24 for EFV patients. The percent of patients with >200 mg/dL TG at week 24 was 30% for NFV patients and 32% for EFV patients. The percent with >500 mg/dL TG was 3% for NFv and 6% for EFV. None of these differences were significant at the 24 week analysis.
Total cholesterol >240 mg/dL was 4% in the NFV group at baseline and 19% at week 24 and for EFV patients it was 2% at baseline and 16% at week 24.
In sum, the authors reported that using multivariate analysis the regimen used (NFV) was a significant factor in predicting LDL >130 at week 24; but for predicting LDL >160 at week 24 baseline LDL and not the regimen (NFV or EFV) predict >160 LDL. The authors conclude that the differences in lipids between the 2 groups at week 24 were not great enough to influence therapy choice. Perhaps longer term followup would be helpful.
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