Insulin Resistance Impairs Rapid Virologic Response to Interferon-based Therapy in HIV-HCV Coinfected Patients


HIV and AIDS Main Section Hepatitis C Main Section HIV-HCV Coinfection Main Section

By Liz Highleyman

Numerous factors contribute to optimal response to interferon-based therapy for chronic hepatitis C virus (HCV) infection, including HCV genotype, baseline HCV viral load, doses and duration of therapy, and degree of early response. In addition, HIV-HCV coinfected patients respond less well than those with HCV monoinfection.

Another factor that has been shown to predict poor response in HCV monoinfected individuals is insulin resistance, a condition in which the body's cells do not respond normally to insulin.

As reported in the April 23, 2008 issue of AIDS, Italian researchers conducted a study to investigate the association between insulin resistance and rapid virologic response (RVR) in coinfected patients.

The study included 74 consecutively enrolled HIV-HCV coinfected individuals who started hepatitis C treatment with 180 mcg/week pegylated interferon alfa-2a (Pegasys) plus 1000-1200 mg/day weight-based ribavirin. Most (about 80%) were men, the mean age was 42 years, about half had advanced fibrosis (METAVIR stages F3-F4), and half were infected with hard-to-treat HCV genotypes 1 or 4.

RVR was defined as undetectable HCV RNA after 4 weeks of therapy. Insulin resistance was defined according to the homeostasis model assessment of insulin resistance (HOMA-IR). Fasting levels of plasma insulin and glucose were measured on the first day of treatment.

Results

• 30 patients (40.5%) achieved rapid virological response at week 4.

• In a multivariate analysis, the independent predictors of RVR were:
• HCV genotype 1 or 4 vs 2 or 3 (adjusted odds ratio 0.18);

• Baseline HCV RNA < 400,000 IU/mL (adjusted odds ratio 0.229);

• HOMA-IR score greater than 3.00 (adjusted odds ratio 0.1).

Conclusion

Based on these findings, the study authors suggested that the HOMA-IR score should be "evaluated and possibly corrected" -- for example, using dietary modification or insulin-sensitizing medications -- before coinfected patients start anti-HCV therapy.

5/13/08

Reference
P Nasta, F Gatti, M Puoti, and others. Insulin resistance impairs rapid virologic response in HIV/hepatitis C virus coinfected patients on peginterferon-alfa-2a. AIDS 22(7): 857-861. April 23, 2008.