HIV-positive individuals who are coinfected with hepatitis C virus (HCV), have significantly lower total cholesterol and LDL cholesterol, according to a US study published in the May edition of HIV Medicine.
Lower total and LDL cholesterol have been observed in HCV monoinfected individuals soon after infection with HCV, and low total cholesterol is common in end stage liver disease and is a poor prgnostic marker for individuals with biopsy-proven cirrhosis. There are, however, few data describing the relationship between HCV coinfection and metabolic changes in HIV-positive individuals treated with HAART. Therefore, investigators from the US Veteran Ageing Cohort 3 Site Study (VACS 3) conducted a retrospective analysis of the records of the 881 HIV-positive individuals.
The investigators compared total cholesterol, LDL cholesterol, HDL cholesterol and triglycerides between the HCV-infected and HCV-negative patients. Variables included in the investigators’ model included HCV antibody status, use of anti-HIV drugs by class, CD4 cell count, HIV viral load, glucose level, use of lipid lowering drugs, race, gender, age, liver function, alcohol and drug use, and HIV risk group.
Of the 881 individuals enrolled in the VACS cohort 700 had had an HCV antibody test performed, with 300 (42.8%) testing HCV-positive, and 400 (57.2%) HCV-negative. HCV-positive and negative patients had comparable ages (47.8 years versus 49.7 years), however there were significant racial differences, with more HCV-positive patients being non-white (80% versus 20%). In addition, HCV-positive individuals were significantly more likely to report injecting drug use (62% versus 13%).
In multivariate analysis, the investigators found that being HCV-positive was independently associated with lower total cholesterol (p=0.001), and lower LDL cholesterol (p
Controlling for variables including use of HAART, glucose level, binge drinking, liver function, current drug use, HIV viral load and CD4 cell count, HCV infected patients had a predicted LDL cholesterol level 18.99mg/dL lower than HCV-negative individuals. Controlling for the same variable, predicted total cholesterol levels were 13.65mg/dL lower in the HCV coinfected patients than the HCV-negative individuals. The investigators note that this reduction in LDL and total cholesterol observed in the HCV-infected patients was large enough to be of clinical significance.
The investigators noted, however, that the individual classes of anti-HIV medication could significantly increase lipid levels, even in the presence of HCV infection. Total cholesterol increased by 25.16mg/dL, and LDL cholesterol by 18.44mg/dL in patients receiving a protease inhibitor. NRTI use increased LDL cholesterol, and NNRTI use significantly increased total cholesterol and triglycerides. The investigators also found that the use of fibrates (p
”HCV was independently associated with lower total cholesterol and LDL cholesterol, and PI use was associated with increased total cholesterol, LDL and triglyceride levels”, comment the investigators. They add that the reduction in LDL cholesterol seen in HCV coinfected patients was of a level “similar…to that observed with most nonstatin cholesterol-lowering medication and exceeds the reduction normally achieved by lifestyle modification in patients with hypercholesterolaemia.”
Although it is not known precisely how HCV lowers LDL and total cholesterol, the investigators speculate that it may because HCV enhances lipid uptake by cells, or because HCV infection impairs VLDL synthesis in liver cells.
”HCV infection is associated with clinically significant lower LDL and total cholesterol levels, and with a decreased use of lipid-lowering medications despite the fact that 63.3% received PIs”, conclude the investigators, who recommend that doctors “should consider testing for HCV in HIV-infected patients with low cholesterol levels.”
Further information on this website
Metabolic changes on HAART - overview
Hepatitis C - overview
Polgreen PM et al. Association of hypocholesterolaemia with hepatitis C virus infection in HIV-infected people. HIV Medicine 5: 144-150, 2004.