Therapeutic response to peg-IFN-alpha-2b and ribavirin in HIV/HCV co-infected African-American and Caucasian patients as a function of HCV viral kinetics and interferon pharmacodynamics

Lynn Rozenberg, Bart L. Haagmans, Avidan U. Neumann, Grace Chen, Mary McLaughlin, Rachel S. Levy-Drummer, H. Masur, Robin L. Dewar, Peter Ferenci, Marcelo Silva, Maria S. Viola, Michael A. Polis, Shyam Kottilil

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

METHOD:: In this study we sought to characterize the relationship between several pharmacokinetic and pharmacodynamic parameters and virologic responses among HIV/hepatitis C virus genotype-1 co-infected patients receiving pegylated interferon-alpha-2b (peg-IFN2b) and ribavirin. We also tried to establish the underlying mechanisms that lead to poor sustained virologic responder rates observed with African-Americans against Caucasians and compared their results with those observed in a cohort of hepatitis C virus mono-infected patients. RESULTS:: Among our studied population, a viral decline of more than 1.0 log at day 3 combined with viral load of less than 5.0 log IU/ml at day 28 predicted sustained virologic responders with negative predictive value 100% and positive predictive value 100%. African-Americans had significantly (P < 0.01) slower hepatitis C virus viral kinetics as compared to Caucasians. However, peg-IFN2b concentrations and pharmacokinetic parameters, peg-IFN2bmax and peg-IFN2b half-life, were similar in both groups and did not predict sustained virologic responders. Nevertheless, the pharmacodynamic parameter EC50, estimated from nonlinear fitting of the viral kinetics together with peg-IFN2b concentration data, showed that HIV/ hepatitis C virus co-infected African-Americans have lower sensitivity to interferon-alpha thus giving rise to slower viral decline. The combined pharmacokinetic/pharmacodynamic parameter IFNmax/EC90 was an excellent predictor of sustained virologic responders, thus showing the importance of maintaining peg-IFN2b levels above EC90 to achieve successful treatment. CONCLUSION:: Further studies are needed to evaluate whether these pharmacodynamic predictions are a result of differential host response to peg-IFN2b or other viral factors conferring relative resistance to peg-IFN2b.

Original languageEnglish
Pages (from-to)2439-2450
Number of pages12
JournalAIDS
Volume23
Issue number18
DOIs
StatePublished - 27 Nov 2009

Keywords

  • HCV viral kinetics
  • HIV co-infection
  • Interferon pharmacodynamics

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