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Journal of Virology, February 2003, p. 1940-1950, Vol. 77, No. 3
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.3.1940-1950.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Impact of Highly Active Antiretroviral Therapy and Immunologic Status on Hepatitis C Virus Quasispecies Diversity in Human Immunodeficiency Virus/Hepatitis C Virus-Coinfected Patients

Jennifer M. Babik and Mark Holodniy1,2*

Division of Infectious Diseases and Geographic Medicine, Stanford University School of Medicine, Stanford, California 94305,1 AIDS Research Center, Veterans Affairs Palo Alto Health Care System, Palo Alto, California 943042

Received 8 May 2002/ Accepted 30 October 2002

This study analyzes the effect of highly active antiretroviral therapy (HAART), and thus immunologic status, on hepatitis C virus (HCV) load and quasispecies diversity in patients coinfected with the human immunodeficiency virus (HIV) and HCV. Three cohorts of coinfected patients were analyzed retrospectively over a period of 7 to 10 months: group A was antiretroviral drug naïve at baseline and then on HAART for the remainder of the study, group B did not receive antiretroviral therapy at any point, and group C was on HAART for the entire study. HCV quasispecies diversity was analyzed by sequencing hypervariable region 1. In a longitudinal analysis, there was no significant change from baseline in any immunologic, virologic, or quasispecies parameter in any of the three groups. However, in comparison to groups A and B, group C had significantly higher CD4+- and CD8+-cell counts, a trend toward a higher HCV load, and significantly increased number of HCV clones, entropy, genetic distance, and ratio of nonsynonymous substitutions per nonsynonymous site to synonymous substitutions per synonymous site (Ka/Ks). In addition, CD4+-cell count was positively correlated with HCV load, genetic distance, and Ka. Interestingly, patients infected with HCV genotype 2 or 3 had a significantly higher CD4+-cell count, HCV load, genetic distance, and Ka/Ks than those infected with genotype 1. These results suggest that there is no immediate effect of HAART on HCV but that, with prolonged HAART, immune restoration results in an increase in HCV load and quasispecies diversity.

* Corresponding author. Mailing address: AIDS Research Center, VA Palo Alto Health Care System, 3801 Miranda Ave. (132), Palo Alto, CA 94304. Phone: (650) 852-3408. Fax: (650) 858-3978. E-mail: holodniy{at}stanford.edu.

Journal of Virology, February 2003, p. 1940-1950, Vol. 77, No. 3
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.3.1940-1950.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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