HIV/HCV co-infected individuals with higher “bad” LDL cholesterol levels are more likely to respond successfully to anti-hepatitis C treatment than those with lower levels of LDL. While several previous studies had shown higher LDL to predict better treatment response in hepatitis C-monoinfected individuals, this retrospective study – reported in the May 11 issue of AIDS – is the first to show a similar effect in co-infected individuals.
In a growing number of studies in hepatitis C virus monoinfected patients, better response to pegylated interferon and ribavirin treatment has been seen in patients with high baseline serum levels of low-density lipoprotein cholesterol (LDL-C). It has been suggested that the cellular receptor for LDL cholesterol also functions as a receptor for hepatitis C, so that there is competition for binding, with higher LDL levels resulting in less attachment of hepatitis C to cells.
However, until now, this has not been studied in HIV/hepatitis C coinfected patients, in whom lipid disorders are common and response to anti-hepatitis C therapy is relatively poor (27–49% show a sustained virologic response). (Other links have been found between coinfection and lipid disorders – for instance, lipid increases tend to be lower and less common in coinfected individuals).
In this retrospective study, Spanish investigators assessed the relationship between baseline lipid levels and response to anti-hepatitis C therapy in 260 coinfected patients treated with pegylated interferon and ribavirin. The study group was drawn from a cohort of 3564 coinfected adult patients at ten Spanish hospitals, followed between October 2001 and February 2005. Of these, 339 received anti-hepatitis C treatment during follow-up, and 272 met inclusion criteria: available retrospective lipid profiles, first use of anti-hepatitis C therapy, and no use of lipid-lowering drugs during therapy or during the previous three months.
LDL cholesterol levels were not measured by direct assay, but estimated from total serum cholesterol, high density lipoprotein (HDL) cholesterol and triglyceride levels according to the formula: LDL = total cholesterol – HDL cholesterol – (triglycerides/5). In twelve patients, high triglyceride levels (> 400 mg/dl) made this estimate impossible, and they were excluded from analysis. This left 260 patients in the study group (80% of whom were male), with the following median characteristics: age 40 years, body mass index (BMI) 23, hepatitis C viral load 5.80 log10, HIV viral load 80 copies/ml, CD4 cell count 520 cells/mm3, total serum cholesterol 166 mg/dl, LDL cholesterol 90 mg/dl, HDL cholesterol 44 mg/dl, triglycerides 128 mg/dl. One hundred and thirty-seven (53%) had the harder-to-treat hepatitis C genotype 1, one (0.4%) genotype 2, 100 (39%) genotype 2, and 21 (8%) genotype 4.
All patients were treated with pegylated interferon and ribavirin. Length of treatment was 48 weeks (or, for some patients with genotype 3, 24 weeks at the physician's discretion); treatment was discontinued early in nonresponders. Ribavirin doses were 800–1200 mg/day. Response was primarily measured by sustained virologic response at 24 weeks after completion of treatment; early virologic response at week 12 and end-of-treatment response were also evaluated.
SVR was achieved in 102 (39%) of patients overall: 38 (24%) of the 158 patients with genotypes 1 or 4, and 64 (63%) of the 101 with genotypes 2 or 3. Rates of sustained virological response were at least twice as high in patients with LDL cholesterol levels 100 mg/dl or more, independent of all other variables. In the study group overall, 49 patients (44%) patients with LDL cholesterol levels 100 mg/dl or more showed sustained virological response, compared with 53 (36%) with lower values (adjusted odds ratio [AOR]: 2.51; 95% confidence interval [CI]: 1.40–4.87; p = 0.003).
This association was independent of the remaining predictors of sustained virological response: genotypes 2–3, plasma hepatitis C viral load of 600 000 iu/ml or less, exposure to at least 80% of the planned therapy, and lack of concomitant antiretroviral therapy. No significant associations were found with other variables including other lipid levels, CD4 cell count, ribavirin dose, or degree of fibrosis/cirrhosis.
Higher rates of early virological response and end of treatment response were also seen at LDL cholesterol levels ≥100 mg/dl. In patients with genotype 1 only, the rate of sustained virological response was 31% for LDL cholesterol ≥ 100 mg/dl vs. 17% for LDL cholesterol
One possible confounder is that total and LDL cholesterol levels decline with increasing severity of liver disease, and treatment discontinuation rates may also increase with greater liver disease, due to decreased tolerability. However, in this as in most other studies, sustained virological response rates were similar across all degrees of liver fibrosis and cirrhosis.
Despite the retrospective design of this study, the researchers conclude that they have demonstrated "for the first time that higher serum LDL cholesterol levels prior to therapy … are associated with sustained virological response in HIV/hepatitis C-coinfected patients, as in hepatitis C virus monoinfection."
Reference:
del Valle J et al. Baseline serum low-density lipoprotein cholesterol levels predict response to hepatitis C therapy in HIV/hepatitis C virus coinfected individuals. AIDS 22: 923-930, 2008.