Hepatitis C virus (HCV) quasispecies complexity and selection in HCV/HIV-coinfected subjects treated with interferon-based regimens.
BACKGROUND
Coinfection with hepatitis C virus (HCV) and human immunodeficiency virus (HIV) has emerged as a major cause of morbidity and mortality due to liver disease. Interferon-based therapy response rates have been disappointingly low. Baseline HCV complexity and the relationship between complexity and viral kinetic parameters has not been well described in HCV/HIV-coinfected subjects.


METHODS
A subset of patients enrolled in the AIDS Clinical Trials Group 5071 trial underwent sampling to evaluate viral kinetics and changes in HCV complexity. Early kinetic parameters, baseline complexity, and treatment outcomes--including rapid viral response (RVR), early viral response (EVR), and sustained viral response (SVR)--were evaluated. HCV-monoinfected subjects were matched to HCV/HIV-coinfected subjects.


RESULTS
Baseline complexity was determined in 108 HCV/HIV-coinfected subjects and in 13 HCV-monoinfected control subjects. Quasispecies complexity was a mean of 2.24 bands for HCV/HIV-coinfected subjects and a mean of 1.90 bands for HCV-monoinfected subjects (P = .14). Lower baseline complexity was associated with EVR (P = .04) and approached statistical significance for SVR. In patients who underwent viral kinetic modeling, a decrease in complexity was associated with RVR (P = .03) and was independent of the correlation between first-phase viral decline efficiency and RVR.


CONCLUSIONS
Baseline HCV complexity is an independent predictor of EVR in HCV/HIV-coinfected subjects. A decrease in complexity occurs by 4 weeks after the initiation of interferon-based therapy and is associated with RVR. These findings may enhance the predictive modeling of treatment outcome in HCV/HIV-coinfected patients.
Sherman
Kenneth E
KE
University of Cincinnati College of Medicine, Cincinnati, Ohio 45267-0595, USA. Kenneth.sherman@uc.edu
Rouster
Susan D
SD
Stanford
Sandra
S
Blackard
Jason T
JT
Shire
Norah
N
Koziel
Margaret
M
Peters
Marion
M
Chung
Raymond T
RT
D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000150:complications*; D016174:Hepacivirus / Q000145:classification* / Q000235:genetics* / Q000302:isolation & purification; D006526:Hepatitis C / Q000150:complications* / Q000188:drug therapy* / Q000821:virology; D020180:Heteroduplex Analysis / Q000379:methods; D006801:Humans; D007372:Interferons / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome
D000998:Antiviral Agents; D007372:Interferons