Coinfection

CROI 2009: High HCV Viral Load Is Associated with an Increased Risk of Death in HIV-HCV Coinfected Individuals

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In contrast with HIV, most studies to date indicate that hepatitis C virus (HCV) viral load is not associated with disease progression. But this may not be the case for HIV-HCV coinfected individuals, according to a study presented at the 16th Conference on Retroviruses and Opportunistic Infections (CROI 2009) last month in Montreal.

Jürgen Rockstroh and colleagues -- who previously reported that being HCV antibody positive was not associated with AIDS progression, but was linked to an increased risk of liver-related death in people with HIV -- conducted a study to assess the influence of HCV viral load and genotype on hepatitis C and HIV disease progression and response to antiretroviral therapy.

The researchers calculated rates of death due to any cause and liver-related death, comparing patients with high (> 500,000 IU/mL or more), low (< 500,000 IU/mL), and undetectable (< 615 IU/mL) HCV viral load.
The analysis included all 1952 HIV-HCV coinfected participants in the EuroSIDA cohort, a prospective observational cohort of more than 16,000 HIV patients, mostly from European countries.

Within this group, 1537 participants (78.7%) had detectable HCV RNA, including 821 (42.0%) with high and 716 (36.6%) with low HCV viral load; 415 people (21.2%) had undetectable HCV viral load. Among the HCV RNA positive patients, a majority (52.0%) had hard-to-treat HCV genotype 1, 3.4% had genotype 2, 30.3% had genotype 3, and 14.2% had genotype 4. Less than 2% had ever received interferon-based hepatitis C treatment.

In multivariate models, the researchers adjusted for potential confounding factors including sex, age, race/ethnicity, HIV transmission risk group, CD4 cell count, history of AIDS diagnosis, type of antiretroviral therapy, region of Europe, and concurrent hepatitis B. They were not able to control for liver function, degree of fibrosis, or alcohol use because EuroSIDA did not collect complete data over the full study period.

Results

"HIV-HCV coinfected patients with HCV viremia had an increased incidence of liver-related death," the investigators concluded. "Moreover, HCV genotype 2 and 3 were associated with decreased overall-death and liver-related deaths."

This presentation led to some debate, given that prior research has not shown a similar association between HCV viral load and mortality in HCV monoinfected individuals, nor a link between HCV genotype and response to HIV treatment (although genotype plays a clear role in response to interferon-based therapy for hepatitis C).

In response to these concerns, Rockstroh suggested that the effect of HCV viral load on mortality may be more apparent in HIV-HCV coinfected patients, who tend to have higher HCV RNA levels and experience more rapid liver disease progression than people with HCV alone.

3/03/09

Reference

Jürgen Rockstroh, L Peters, V Soriano, and others. High HCV Is Associated with an Increased Risk for Mortality in HIV/HCV-co-infected Individuals. 16th Conference on Retroviruses and Opportunistic Infections (CROI 2009). Montreal, Canada. February 8-11, 2009. Abstract 101.