Hepatitis C Virus (HCV) Quasispecies Complexity and Selection in HCV/HIV-Coinfected Subjects Treated with Interferon-Based Regimens

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J Infect Dis. 2010 Jan 27. [Epub ahead of print]

Hepatitis C Virus (HCV) Quasispecies Complexity and Selection in

HCV/HIV-Coinfected Subjects Treated with Interferon-Based Regimens.

Sherman KE, Rouster SD, Stanford S, Blackard JT, Shire N, Koziel M, s M,

Chung RT.

University of Cincinnati College of Medicine, Cincinnati, Ohio; 2Infectious

Disease Epidemiology, Merck & Co, Inc, North Wales, Pennsylvania; 3Department of

Medicine, Beth Israel Deaconess Medical Center, and 4Harvard Medical School,

Massachusetts General Hospital, Boston; 5Division of Gastroenterology,

University of California-San Francisco, San Francisco.

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 ([Formula: see text]). Lower baseline complexity was associated with

EVR ([Formula: see text]) and approached statistical significance for SVR. In

patients who underwent viral kinetic modeling, a decrease in complexity was

associated with RVR ([Formula: see text]) and was independent of the correlation

between first-phase viral decline efficiency and RVR. Conclusion. 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.

PMID: 20105080 [PubMed - as supplied by publisher]