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 HIV and Coverage of the
17th Conference on Retroviruses and
Infections (CROI 2010)
 February 16 - 19, San Franciso, California
Leakage of Gut Bacteria Linked to Poor Hepatitis C Treatment Response in HIV/HCV Coinfected Patients

SUMMARY: HIV/HCV coinfected individuals who did not respond well to interferon-based therapy for hepatitis C showed evidence of greater microbial translocation -- leakage of bacteria due to HIV damaging the gut -- than early responders, although T-cell activation did not differ, according to a poster presentation at the 17th Conference on Retroviruses & Opportunistic Infections (CROI 2010) last week in San Francisco.

By Liz Highleyman

HIV/HCV coinfection is associated with more rapid liver disease progression and poorer response to interferon-based therapy compared with hepatitis C virus (HVC) alone, but the pathogenic mechanisms underlying these disparities are not well understood.

One of the earliest manifestations of HIV disease is injury to the lining of the intestines as HIV infects the many CD4 T-cells there. This damage can allow microbes residing in the gut to leak out. As these bacteria and their toxins such as lipopolysaccharide (LPS) enter the bloodstream a process known as microbial translocation they trigger generalized immune activation, and the resulting inflammatory response appears to contribute to a variety of non-AIDS conditions seen in people with HIV.

Given that laboratory and animal studies have shown that exposure to LPS can result in liver inflammation and fibrosis, Giusi Maria Bellistri and colleagues from Italy hypothesized that microbial translocation might be relevant to hepatitis C disease progression and treatment response in HIV/HCV coinfected patients, possibly related to immune hyper-activation.

In this cross-sectional study, the researchers analyzed 98 HIV/HCV coinfected patients on combination antiretroviral therapy (ART) who had HIV viral loads <50 copies/mL. All participants started hepatitis C treatment using pegylated interferon alfa plus weight-adjusted ribavirin (1000-1200 mg).

The researchers looked at early virological response, defined as HCV RNA < 15 IU/mL at week 12 of therapy. Advanced fibrosis was defined as a Knodell score of F3 to F4 based on liver biopsy, or liver stiffness >12.5 kPa using FibroScan. They also looked at LPS levels and markers of immune activation, including HLA-DR, CD38, CD4/CD8 and soluble CD14 (sCD14), a protein that plays a key role in responding to LPS.


54 patients (55%) achieved early virological response (EVR) at week 12, while 44 (45%) were categorized as early non-responders (non-EVR).
Plasma sCD14 levels were significantly correlated with advanced fibrosis and with hard-to-treat HCV genotypes 1 and 4, and vice versa.
Markers of microbial translocation plasma LPS and sCD14 were significantly more elevated in the non-EVR group than in the EVR group.
However, levels of CD8 T-cell activation markers HLA-DR and CD38 did not differ significantly between the 2 groups.

Based on these findings, the researchers concluded, "HIV/HCV coinfected patients lacking early response to HCV therapy display heightened microbial translocation."

"Patterns of microbial translocation are associated [with] negative clinical and virological prognostic markers of HCV disease," they continued. By supporting HIV-related microbial translocation as a pathway of accelerated liver disease, these data also allow speculation that microbial translocation is an "adjunctive early biomarker of HCV disease progression and treatment outcome.

San Paolo Hosp, Univ of Milan, Italy; Inst of Infectious and Tropical Diseases, Univ of Brescia, Italy.


Increased Microbial Translocation Is Associated with Lack of Early Virological Response to Pegylated Interferon + Ribavirin Treatment in HIV/HCV Co-infected Patients with Good Viro-Immunological Response to HAART GM Bellistrì, I Barbetta, F Gatti, and others. 17th Conference on Retroviruses & Opportunistic Infections (CROI 2010). San Francisco. February 16-19, 2010. (Abstract 654).



















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