Blood Lipid Levels and Insulin Resistance Predict Response to Interferon-based Therapy in HIV-HCV Coinfected Patients

By Liz Highleyman

Response to interferon-based therapy for chronic hepatitis C virus (HCV) infection varies widely across individuals, but tends to be poorer in people with HIV-HCV coinfection. Some factors associated with better response are well established -- including having HCV genotypes 2 or 3 (rather than 1 or 4) and a low baseline HCV viral load -- but others have been less extensively studied.

As reported at the 48th International Conference on Antimicrobial Agents and Chemotherapy (ICAAC 2008) in late October, Paola Nasta and colleagues analyzed the association between baseline metabolic parameters and response rates in 96 HIV-HCV coinfected individuals undergoing hepatitis C treatment with pegylated interferon plus ribavirin.

Most (83%) were men, the median age was 43 years, 54% had HCV genotypes 1 or 4, 58% had advanced liver fibrosis (Metavir stage F3-F4), and 29% had cirrhosis. Nearly 90% were on HAART, three-quarters of them using a protease- inhibitor (PI)-based regimen.

The investigators assessed rapid virological response (RVR; undetectable HCV RNA at week 4 of treatment), early virological response (EVR) at week 12, and sustained virological response (SVR; continued undetectable HCV 24 weeks after completing therapy).

Fasting total cholesterol, LDL ("bad") and HDL ("good") cholesterol, and triglycerides levels were measured in all patients at baseline. To assess insulin resistance, the researchers determined HOMA-IR scores.

Results

• Overall, 42% of participants achieved RVR (22% for genotypes 1 or 4; 64% for genotypes 2 or 3);

• 62% achieved EVR (39% and 91% for the respective genotype groups);

• 37% achieved SVR (19% and 64%, respectively).

• In a multivariate analysis, genotype was a predictor for RVR, EVR, and SVR.

• Triglyceride level > 150 mg/dL was significantly associated with RVR and EVR, but not SVR.

• LDL level was only a significant factor for RVR.

• HOMA-IR score < 3 was associated with response at all 3 time points.

• Baseline HCV RNA < 400,000 IU/mL was an additional predictor for SVR.

"Metabolic parameters are key factors to predict RVR, EVR, and SVR in HIV-HCV coinfected subjects treated with [pegylated interferon/ribavirin]," the researchers concluded.

They added that their analysis "suggest[s] a direct role" for hypertriglyceridemia (elevated triglycerides), and a possible impact of HAART-related metabolic impairment on response to hepatitis C treatment.

Inst. of Infectious and Tropical Diseases, Univ. of Brescia, Brescia, Italy.

12/9/08

Reference
P Nasta, G Gatti, G Cologni, and others. Triglycerides, LDL Cholesterol and HOMA Score Predict the Virological Response in HIV/HCV Co-infected Patients Treated with PegInterferon alfa2a/Ribavirin (PegIFN/RBV). 48th International Conference on Antimicrobial Agents and Chemotherapy (ICAAC 2008). Washington, DC. October 25-28, 2008. Abstract H-2318.