Coinfection

HIV/HCV Coinfected People with Insulin Resistance Do Not Respond as Well to Interferon-based Therapy

After controlling for other risk factors, insulin resistance was an independent predictor of poor response to interferon plus ribavirin combination therapy for chronic hepatitis C in people with HIV, according to a Spanish study published in the June 23, 2010 Journal of Acquired Immune Deficiency Syndromes. The researchers suggested that management of insulin resistance may enhance response rates in the HIV/HCV coinfected population.

HIV/HCV coinfected people tend to experience faster liver disease progression and do not respond as well to interferon-based therapy as HIV negative people with hepatitis C alone.

A number of factors predict poor treatment response in coinfected and HCV monoinfected patients alike, including HCV genotype, baseline HCV viral load, and extent of liver fibrosis or cirrhosis. Several studies have also implicated insulin resistance, though results have not been consistent.

Pablo Ryan and colleagues retrospectively evaluated the effect of insulin resistance on rates of sustained virological response (SVR) in HIV/HCV coinfected patients, reviewing clinical records of coinfected patients treated with interferon plus ribavirin at Hospital Gregorio Maranon in Madrid between July 2000 and March 2007.

Among the 218 treated coinfected patients, 162 had available baseline insulin resistance information and 134 were included in the on-treatment analysis. Most (67%) had hard-to-treat HCV genotypes 1 or 4 and 36% had advanced (stage F3-F4) liver fibrosis.

Insulin resistance was defined as a homeostasis model assessment (HOMAR) value >3.8. SVR was defined as an undetectable HCV RNA at 24 weeks after completion of treatment.

Results

• 67 patients (50%) achieved sustained virological response:
• 38% for those with genotypes 1 or 4;
• 79% for those with genotypes 2 or 3.
• Patients with insulin resistance had a significantly lower SVR rate (odds ratio [OR] 0.33; P = 0.006).
• Independent variables that predicted SVR were:
• HCV genotype 2 or 3 (OR 6.7; P < 0.001);
• Absence of insulin resistance at baseline (OR 3.3; P = 0.008);
• Lower nadir (lowest-ever) CD4 T-cell count (OR 1.002; P = 0.047).

These findings, the researchers concluded, "suggest that insulin resistance is an important determinant of SVR in HIV/HCV coinfected patients treated with interferon plus ribavirin."

"Strategies to modify insulin resistance should be explored to enhance SVR during anti-HCV therapy," they recommended.

Investigator affiliations: Department of Microbiology, Hospital Gregorio Maranon, Madrid, Spain; Biomedical Research Foundation, Hospital Gregorio Maranon, Madrid, Spain; Instituto de Salud Carlos III, Majadahonda, Spain.

7/13/10

Reference

P Ryan, S Resino, P Miralles, and others. Insulin Resistance Impairs Response to Interferon Plus Ribavirin in Patients Coinfected With HIV and Hepatitis C Virus. Journal of Acquired Immune Deficiency Syndromes (Abstract) June 23, 2010 (Epub ahead of print).