HCV RNA decline in the first 24 h exhibits high negative predictive value of sustained virologic response in HIV/HCV genotype 1 co-infected patients treated with peginterferon and ribavirin

Antiviral Res. 2011 Apr;90(1):92-7. doi: 10.1016/j.antiviral.2011.02.013. Epub 2011 Mar 2.

Abstract

Background: Treatment with Peg-interferon and ribavirin (PEG-IFN/RBV) for HIV patients co-infected with hepatitis C virus (HCV) genotype 1 has suboptimal rates of response. Viral kinetics has emerged as one of the best prognostic factors of treatment outcome.

Methods: Twenty HIV/HCV genotype 1 co-infected patients in treatment with PEG-IFN/RBV, had blood drawn at baseline, 24 h, 4, 12, 24, 48, and 72 weeks. HCV-RNA levels were evaluated at each time point. ROC curves were used to evaluate the log10 HCV-RNA decay at 24 h that exhibits the best predictive value of achieving response. Genomic characterization of HCV NS5A at both interferon sensitivity-determining region (ISDR) and protein-kinase binding (PKRBD) domains were performed in order to evaluate its heterogeneity and association with 24 h HCV-RNA decay and SVR.

Results: Non-responder patients exhibited a mean of 0.7 log10 (SD 0.74 log10) HCV-RNA decay at 24 h, whereas responder-patients presented 1.6 log10 (SD 0.28 log10), p = 0.04. A reduction in HCV viral load from baseline to 24 h of < 1.4 had a negative predictive value for achieving SVR of 100% and a positive predictive value of 50%. HCV genotype 1 isolates from patients with a decrease of HCV-RNA at 24 h > 1.4 log10, exhibited 3.1(SD 1.5) amino acids substitutions in ISDR and 4.8(SD 2.3) in PKRBD regions and 1.6(SD 0.7) and 2.4(SD 1.3), respectively, in those patients presenting lower reduction in HCV-RNA.

Conclusions: HIV/HCV genotype 1 co-infected patients with a decrease in HCV-VL at 24 h > 1.4 log10 are more likely to achieve SVR when treated with PEG-IFN/RBV than those with lower levels of HCV-RNA decay. Along with other host-related and viral-related prognostic factors in HIV/HCV co-infected patients, this very early time point of evaluation could be of relevance in the management of HCV-specific treatment.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antiviral Agents / administration & dosage*
  • Female
  • Genotype
  • HIV Infections / complications*
  • Hepacivirus / classification
  • Hepacivirus / genetics
  • Hepacivirus / isolation & purification*
  • Hepatitis C / complications*
  • Hepatitis C / drug therapy*
  • Humans
  • Interferon alpha-2
  • Interferon-alpha / administration & dosage
  • Male
  • Middle Aged
  • Polyethylene Glycols / administration & dosage
  • RNA, Viral / blood*
  • Recombinant Proteins
  • Ribavirin / administration & dosage
  • Sequence Analysis, DNA
  • Time Factors
  • Treatment Outcome
  • Viral Load*
  • Viral Nonstructural Proteins / genetics

Substances

  • Antiviral Agents
  • Interferon alpha-2
  • Interferon-alpha
  • RNA, Viral
  • Recombinant Proteins
  • Viral Nonstructural Proteins
  • Polyethylene Glycols
  • Ribavirin
  • NS-5 protein, hepatitis C virus
  • peginterferon alfa-2a