HCV/HIV Coinfected have more viral diversity than HCV infected; CD4s May Be Key in Immune Control

     Lorna M Dove, VAMC, Univ of CA, San Francisco, San Francisco, CA; Yume Phung, Janelle Wrock, Michael Kim, VAMC, San Francisco, CA; Wright L Teresa, VAMC, Univ of CA, San Francisco, CA

In this small study Lorna Dove compared

Samples were looked at 12 months apart for viral complexity and diversity. Coinfected patients had more diversity at 12 month time point. And persons with <200 CD4s had significant difference in diversity compared to those with <200 CD4s. Dove suggests that immune compromise may lead to more viral diversity, suggesting that CD4s may have some affect in controling response to HCV.

The pathogenesis of HCV infection in patients coinfected with HIV is not well understood. Patients with coinfection appear to have a more rapid progression to cirrhosis compared to patients with HCV alone. Hypothesis: We propose that viral evolution contributes to the progression of disease through differences in complexity (number of quasispecies) or changes in viral diversity (emergence of new species over time).

(i) to measure changes in viral complexity and diversity in patients with HIV/HCV coinfection,
(ii) to compare these changes to an immune competent population infected with HCV alone.

9 patients with HIV/HCV coinfection were studied (5 with CD4 lymphocytes>200 #/cmm and 4 with CD4 lymphocytes < 200 #/cmm). Five HCV infected patients without HIV were used as controls. Patients were matched for genotype (all genotype 1), and length of follow up (mean 14.4 months). HCV quasispecies were characterized by analysis of a 43 amino acid sequence of the hypervariable region. Samples at two time points one year apart were analyzed for each patient. Ten clones at each time point were examined by HDA and confirmed by sequence analysis. 

Results: (table 1)
Complexity was not significantly different between groups at either time point and did not change with time either in immune competent patients or patients with HIV coinfection. At the 12 month time point, there was a significant difference in diversity in patients with HIV and CD4 lymphocytes>200 compared to controls and also a significant difference noted between coinfected patients with CD4 lymphocytes <200 compared to patients with CD4 lymphocytes >200. No genotype switching was noted. Median HCV RNA levels were signficantly higher in HIV coinfected patients compared to controls at the 12 month time point (p=.02).


1. Evolution of quasispecies was seen in all patients

2. The emergence of new variants and the extinction of old variants were seen in all groups, but most prominent in coinfected patients with severe immunocompromise

3. The overall number of variants did not change in any group.

These data support the hypothesis that immune compromise may be associated with emergence or selection of new viral species over time. This change in viral species may contribute to persistent infection and progression of liver disease.