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Insulin Resistance Reduces the Likelihood of Sustained Response to Hepatitis C Treatment in HIV-HCV Coinfected Patients

By Liz Highleyman

A letter to the editor in the February 1, 2008 Journal of Acquired Immune Deficiency Syndromes added to the evidence that abnormal glucose metabolism contributes to poor response to interferon-based therapy for chronic hepatitis C in HIV-HCV coinfected patients, as has also been demonstrated in HIV negative individuals.

This is a concern, because some antiretroviral drugs used to treat HIV - especially protease inhibitors -- have been associated with insulin resistance (IR) and related conditions including impaired glucose tolerance and type 2 diabetes.

In the present study, Italian researchers evaluated the relationship between IR and virological response during early therapy in HIV-HCV coinfected individuals receiving pegylated interferon plus ribavirin.

As background, the authors noted that the link between IR and HCV may be related to increased tumor necrosis factor production and enhanced expression of suppressor cytokines.

The study included 29 consecutive coinfected patients at a Milan clinic who started pegylated interferon alfa-2a (Pegasys) plus 1000-1200 mg weight-based ribavirin in January 2006. All participants were white men with a median age of 43 years; 10 (34.5%) had IR at baseline, defined as a score > 3.8 according to the homeostasis model assessment of insulin resistance (HOMA-IR) index.

Rapid virological response (RVR) to interferon-based therapy was defined as undetectable HCV RNA (<15 IU/mL) after 4 weeks, while early virological response (EVR) was defined as undetectable HCV viral load at 12 weeks.

Results

• After 3 months of treatment, median ALT and AST levels decreased in both the IR and non-IR groups.

• Patients without IR at baseline were more likely to achieve RVR and EVR than those with IR:

• 8 of the 19 patients (42.1%) without baseline IR achieved RVR, compared with none of the 10 with IR (P < 0.001);

• 16 of the 19 (84.2%) without IR and none with IR achieved EVR.

• The 3 subjects who did not achieve EVR had HCV genotypes 1a, 3a, and 4c/4d.

Conclusion

"In the present study, including only HIV-HCV coinfected subjects, we found subjects without IR at baseline are more likely to reach RVR and EVR than the others," the authors concluded.

They noted that the presence of IR may hamper achievement of RVR and EVR in individuals with HCV genotype 3, which is otherwise known to respond better to anti-HCV therapy.

"These results, obtained on a limited number of subjects, suggest that IR should always be evaluated before starting anti-HCV treatment," the investigators recommended, adding that "the correction of IR, and the consequent recovery of insulin sensitivity, could improve RVR and EVR in the HIV-HCV coinfected population treated with pegylated interferon and ribavirin, and thus should be tentatively attempted before initiating such a regimen."

3/11/08

Reference

M Bongiovanni, R Ranieri, M Casana, and others. Insulin resistance affects early virologic response in HIV-infected subjects treated for hepatitis C infection. Journal of Acquired Immune Deficiency Syndromes 47(2): 258-259. February 1, 2008.