HCV Clearance in Blood Plasma Indicates Eradication in Immune Cells in HIV/HCV Coinfected Patients

SUMMARY: HIV/HCV coinfected individuals who achieve undetectable hepatitis C virus (HCV) RNA in their blood plasma following successful pegylated interferon plus ribavirin treatment for acute or chronic hepatitis C were found to have no signs of residual HCV genetic material in their peripheral blood immune cells, indicating true eradication or cure, according to a report in the June 1, 2010 issue of AIDS.

By Liz Highleyman

Even with the most successful antiretroviral therapy (ART), HIV only can be suppressed to an undetectable level in the blood and other tissues, while viral genetic material remains in latent reservoir cells including CD4 T-cells. Some past studies have found that this is also the case for HCV, but others have been unable to detect replication-capable virus, suggesting that hepatitis C treatment represents a true "cure."

To shed further light on this issue, Emma Page from the Chelsea and Westminster NHS Foundation Trust in London and colleagues looked at HCV RNA persistence in peripheral blood mononuclear cells (PBMCs) of HIV/HCV coinfected individuals who had cleared HCV from their blood plasma. PBMCs are specific types of immune system blood cells in the peripheral circulation, including lymphocytes, monocytes, and macrophages.

This prospective cross-sectional study included 26 HIV positive individuals who had previously been infected with HCV but currently had undetectable plasma HCV viral load:

• 6 had spontaneously cleared HCV without treatment;
• 10 had achieved sustained virological response (SVR) -- or continued undetectable plasma HCV RNA 6 months after completion of treatment -- following 24 weeks of pegylated interferon plus ribavirin for acute hepatitis C;
• 10 had achieved SVR following standard pegylated interferon plus ribavirin treatment for chronic hepatitis C.

The researchers collected blood samples to test for HCV genetic material in both serum and PBMCs. Intracellular HCV was extracted using the QIAamp RNA Blood MiniKit. Reverse transcriptase PCR was performed using a modified COBAS TaqMan HCV test.

They found that none of the participants showed any evidence of HCV RNA persistence in their either serum or their peripheral blood cells.

"Our findings lend support to the view that clearance of HCV RNA from serum in HIV/HCV coinfection indicates eradication from PBMCs," the study authors concluded. "Thus, absence of serum HCV RNA 6 months after the end of therapy can be used as a marker of treatment success for interferon-based therapies."

However, they added, "the advent of small molecule HCV inhibitors may require us to rethink our definitions of response and cure," referring to direct-acting antiviral agents such as HCV protease and polymerase inhibitors currently in development.

Investigator affiliation: Chelsea and Westminster NHS Foundation Trust, London, UK.

6/25/10

Reference
EE Page, A Cox, A Atkins, and MR Nelson. Clearance of hepatitis C virus RNA from serum in HIV/hepatitis C virus coinfection indicates eradication from peripheral blood mononuclear cells. AIDS 24(9): 1267-1271 (Abstract). June 1, 2010.

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