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The Body Covers: The 15th Conference on Retroviruses and Opportunistic Infections

Study Examines Pro-Inflammatory Responses in HIV/HCV-Coinfected Injection Drug Users
An Interview With Camilla Graham, M.D.

By Bonnie Goldman

February 6, 2008

There's nothing like hearing the results of studies directly from those who actually conducted the research. It is these women and men who are transforming HIV treatment and care. In this interview, you'll meet one of these impressive HIV researchers and read an explanation of the study she is presenting at CROI 2008.

Camilla Graham: I'm Cammie Graham. I am at Beth Israel Deaconess Medical Center in Boston, Mass., and also at Vertex Pharmaceuticals in Cambridge. This is a study looking at immune responses in people who are heroin injection drug users --specifically, these people have no cocaine or alcohol use, just heroin -- versus people who are pure methadone users versus people who have no current substance use at all.1 The cohort is divided into people who have HIV/hepatitis C coinfection versus hepatitis C alone.

What we're doing is looking at whether cellular immune responses are affected by exposure to different substances of abuse. This is important because it's felt that both HIV control and, perhaps, progression of liver disease with hepatitis C may be immunologically mediated.

What we found was that heroin injection drug users had lower HIV-specific interferon-gamma immune responses compared to people who did not use any substances. It's felt that interferon-gamma may be an important cytokine-mediating viral control. In the hepatitis C [monoinfected] patients, we found that hepatitis C-specific immune responses to interferon-gamma were actually higher. It's unclear what the impact might be on liver disease progression, because we don't have serial liver biopsies in this group of patients.

We then looked at a very broad array of pro-inflammatory cytokines and chemokines -- proteins that affect the overall inflammation in the body -- to see if these agents had any effect. We found that heroin injection drug users who had HIV and also hepatitis C had changes in a number of these pro-inflammatory markers. Ultimately, what we will need to do is look to see if this actually does affect liver disease progression in these patients.

Bonnie Goldman: Do you have any idea why you saw that with the heroin users?

Camilla Graham: What we think is that the active injection drug use leads to a lot of antigenic stimulation that might be modified by the presence of HIV itself, leading to this pro-inflammatory environment. Other studies and other models have shown that that a pro-inflammatory environment can be associated with worse fibrosis progression, 2 though we don't have clinical correlation in this cohort.

Male Researcher: Every time I look at this [research], you have new cytokines. [Laughs.] I've never heard of TARC [thymus and activation-regulated chemokine] before.

Camilla Graham: That's why I put that nice chart up there. [Editor's note: Dr. Graham is referring to Table 5 of her poster .]

Male Researcher: It was a good idea. I was reading it and thinking, "TARC?"

Camilla Graham: Why did we pick all of those [cytokines and chemokines to investigate]? Because the commercial company that created the Multiplex assay has different proteins that [it has] looked at to make sure that they actually interact and don't interfere with each other with the measurement. This was just a panel [of proteins] that had been verified as willing to play with each other in this system. They're a pretty broad array of important cytokines and chemokines. Ultimately, the reason we did this work was to lay the foundation for looking at predictors of accelerated liver disease progression.

Bonnie Goldman: Thank you.

This transcript has been lightly edited for clarity.


Footnotes

  1. Graham C, Kress M, Edwards D, et al, and members of CHARM. Comparisons between heroin injection drug use and methadone on antigen-specific cellular immune responses in HIV/HCV and HCV infection. In:Program and abstracts of the 15th Conference on Retroviruses and Opportunistic Infections; February 3-6, 2008; Boston, Mass. Abstract 1047.
    View Poster: Download PDF
  2. Cerny A, Chisari FV. Pathogenesis of chronic hepatitis C: immunological features of hepatic injury and viral persistence. Hepatology. September1999;30(3):595-601.




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