Previous Article | Next Article 
Antimicrobial Agents and Chemotherapy, February 2009, p. 615-621, Vol. 53, No. 2
0066-4804/09/$08.00+0 doi:10.1128/AAC.00947-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.
Polymorphism in the Human Major Histocompatibility Complex and Early Viral Decline during Treatment of Chronic Hepatitis C 
,
Leland J. Yee,1,2*
KyungAh Im,1,3
Abdus S. Wahed,3
Teodorica Bugawan,4
Jia Li,4
Shannon L. Rhodes,5
Henry Erlich,4
Hugo R. Rosen,6
T. Jake Liang,7
Huiying Yang,5,
for the Virahep-C Study
Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania,1 Division of Infectious Diseases, Department of Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania,2 Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania,3 Roche Molecular Systems, Inc., Alameda, California,4 Cedars Sinai Medical Center, Los Angeles, California,5 University of Colorado Health Science Center, Denver, Colorado,6 Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland7
Received 8 July 2008/ Returned for modification 15 August 2008/ Accepted 3 October 2008
The dynamics of the viral decline immediately after the start of therapy for chronic hepatitis C virus (HCV) infection may have prognostic potential for ultimate sustained virologic response. Considerable interindividual variability in the decline has been reported, including differences by race. The human major histocompatability complex (MHC) genes encode the human leukocyte antigens, which are important in the immune response to viral infections. We examined whether carriage of specific human MHC alleles are associated with the rate of the early viral decline. Longitudinal viral level data (baseline and days 1, 2, 7, 14, and 28 of treatment), medium resolution MHC genotyping, and random coefficients models were used to examine associations between MHC class I and class II allele carriage and the dynamics of the viral decline in 180 African-Americans (AAs) and 194 Caucasian Americans (CAs) with genotype-1 HCV infection over the first 28 days of treatment with peginterferon 
2a plus ribavirin. Baseline viral levels were similar by race, irrespective of allele carriage. However, the rate of change in the viral decline was associated with both allele and race. Among the four subgroups defined by race and specific allele, the fastest rates of decline were observed (in terms of estimated mean viral declines log10 IU/ml during the first four weeks) in CA noncarriers for A*03 (2.75; P = 0.018), in CA carriers for Cw*03 (2.99; P = 0.046), and in CA noncarriers for DQA1*04 (2.66; P = 0.018) or DQB1*0402 (2.65; P = 0.018). MHC alleles are associated with the viral decline during the first 28 days of peginterferon therapy.
* Corresponding author. Mailing address: Department of Epidemiology, University of Pittsburgh, A511 Crabtree Hall, 130 DeSoto Street, Pittsburgh, PA 15261. Phone: (412) 624-5326. Fax: (412) 624-7397. E-mail: YeeL{at}edc.pitt.edu
Published ahead of print on 13 October 2008.
Supplemental material for this article may be found at http://aac.asm.org/.
Present address: Department of Discovery, Medicine, and Epidemiology, AstraZeneca Pharmaceuticals LP, Wilmington, Delaware.
Contributing members of the Virahep-C Study are listed in the Acknowledgments.
Antimicrobial Agents and Chemotherapy, February 2009, p. 615-621, Vol. 53, No. 2
0066-4804/09/$08.00+0 doi:10.1128/AAC.00947-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.
Copyright © 2009 by the American Society for Microbiology. For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»