LDLr genotype modifies the impact of IL28B on HCV viral kinetics after the first weeks of treatment with PEG-IFN/RBV in HIV/HCV patients

AIDS. 2012 May 15;26(8):1009-15. doi: 10.1097/QAD.0b013e3283528b1c.

Abstract

Objective: To evaluate the effect of low-density lipoprotein receptor (LDLr) and IL28B genotypes on hepatitis C virus (HCV) viral kinetics in the first 4 weeks of treatment with pegylated-interferon (PEG-IFN)/ribavirin (RBV) in HIV patients co-infected with HCV genotype 1.

Methods: HIV patients co-infected with HCV genotype 1 and naïve to PEG-IFN/RBV treatment were enrolled in a prospective study. HCV RNA viral loads were measured at baseline and at weeks 1, 2 and 4 after start of therapy. Differences in viral load decline were evaluated for IL28B (CC versus non-CC) and LDLr (CC versus non-CC) genotypes between baseline and weeks 1, 2 and 4. Additionally, the effect of LDLr genotype on HCV viral decline in IL28B CC genotype patients (CC/CC versus CC/non-CC) was analyzed.

Results: Eighty-seven HIV/HCV genotype 1 co-infected patients were included in the study. Patients carrying the LDLr-CC or IL28B-CC genotypes showed greater HCV viral decline than those with IL28B non-CC or LDLr non-CC genotypes at every time-point analyzed. CC/CC patients had higher rapid virological response (RVR) rates than CC/non-CC patients (41.2 versus 13.3%; P < 0.001). Moreover, at all time points, the CC/CC pattern was associated with greater HCV viral decline than the CC/non-CC genotype (week 1: 1.18 ± 0.51 versus 0.31 ± 0.29, P = 0.041; week 2: 1.55 ± 0.81 versus 0.93 ± 0.73, P = 0.032; week 4: 2.23 ± 1.1 versus 1.5 ± 0.94, P = 0.039).

Conclusion: The LDLr genotype impacts on viral kinetics during the first days of starting treatment with PEG-IFN/RBV in HIV/HCV genotype 1 co-infected patients, and modifies the impact of IL28B on HCV viral decay.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antiviral Agents / therapeutic use
  • Female
  • Genotype
  • HIV Infections / complications
  • HIV Infections / drug therapy
  • Hepacivirus / genetics
  • Hepacivirus / isolation & purification*
  • Hepatitis C / complications
  • Hepatitis C / drug therapy
  • Hepatitis C / genetics*
  • Humans
  • Interferon-alpha / therapeutic use
  • Interferons
  • Interleukins / genetics*
  • Male
  • Polymorphism, Single Nucleotide
  • Prospective Studies
  • RNA, Viral / blood*
  • Receptors, LDL / genetics*
  • Ribavirin / therapeutic use
  • Treatment Outcome
  • Viral Load*

Substances

  • Antiviral Agents
  • interferon-lambda, human
  • Interferon-alpha
  • Interleukins
  • RNA, Viral
  • Receptors, LDL
  • Ribavirin
  • Interferons