Background:  Insulin resistance is associated with poor response to anti-hepatitis C virus (HCV) combination treatment with pegylated interferon alpha (pegINF-α) and ribavirin (RBV) in HCV mono-infected patients. Rapid virologic response is defined as HCV RNA negativization by qualitative polymerase chain reaction (PCR) assay at week 4 of anti-HCV treatment and is reported to  be strongly predictive of sustained virologic response in HCV-mono-infected and HIV/HCV-co-infected subjects.

Methods:  The association between  baseline homeostasis model of assessment (HOMA) calculated as fasting insulin (mIU/L) × fasting glucose (mmol/L) ÷ 22.5 and rapid virologic response was assessed in  HCV/HIV-co-infected patients who started anti-HCV combination treatment with pegINF-α-2a (180 µg/week) +  RBV (1000 to 1200 mg/day). Fasting insulin and glucose plasma level were measured in all patients on the first day of treatment. HCV RNA was measured by quantitative PCR assay (Versant 3.0) at baseline, and HCV RNA by qualitative PCR assay (COBAS 2.0) after 4 weeks of treatment. 

Results:   We enrolled 40 HIV/HCV-co-infected patients who consecutively started pegINF-α-2a + RBV. Their median age was 41.5 years (IQR 37.5 to 45), 8 were female, 16 had advanced fibrosis (F3-4 according to METAVIR classification), and 18 were infected with HCV genotype 2 or 3; 38 were on HAART, of whom 27 had a protease inhibitor (PI) -based regimen; 23 with undetectable HCV RNA by PCR at the fourth week were rapid virologic responders. Rapid virologic responders showed significantly lower HOMA-IR score at baseline (median HOMA 1.33, IQR 0.8 to 2.63 vs 3.41, IQR 1.57 to 5.2.  p = 0.004). Multivariate analysis showed that only HCV genotype 2 or 3 (OR 5.1, 95%CI 1.04 to 25, p = 0.04) and an HOMA-IR >3 (OR 0.12, 95%CI 0.02 to 0.71, p = 0.02) were significantly associated with rapid virologic responders. Exposure to PI was significantly and independently associated with a baseline HOMA >3 (OR 9, 95%CI 1.01 to 80, p = 0.03).

Conclusions:  HOMA-IR seems to be one of the main predictors of rapid virological response in HIV/HCV-co-infected patients, as well as of genotype 2/3. To increase sensitivity to the anti-HCV treatment in HIV/HCV-co-infected subjects, a PI-sparing HAART regimen could be an option.