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

By Liz Highleyman

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

The number of deaths due to any cause during the study period varied according to HCV viral load:

Undetectable HCV RNA: 78 deaths, or 3.12 per 100 person-years (PY) of follow-up;

HCV RNA < 500,000 IU/mL: 96 deaths, 1.74 per 100 PY;

HCV RNA > 500,000 IU/mL: 158 deaths, 4.17 per 100 PY.

After adjusting for potential confounding factors, individuals with undetectable and low HCV viral load had similar rates of all-cause death, but patients with high HCV RNA had about twice the risk (adjusted incidence rate ratio 1.94).

A similar pattern was observed for liver-related deaths:

Undetectable HCV RNA: 17 deaths, or 0.68 per 100 PY;

HCV RNA < 500,000 IU/mL: 32 deaths, 0.58 per 100 PY;

HCV RNA > 500,000 IU/mL: 49 deaths, 1.29 per 100 PY.

Again, in an adjusted analysis, patients with undetectable and low HCV viral load had similar rates of liver-related death, but those with high HCV RNA were at significantly greater risk (adjusted incidence rate ratio 1.77).

After adjusting for other factors, patients with HCV genotypes 2 or 3 had a lower all-cause death rate than those with genotypes 1 or 4, but the difference was statistically significant only for genotype 3.

A similar pattern was seen for liver-related death, but the differences did not reach statistical significance (possibly due to small numbers).

HCV viral load did not significantly affect virological or immunological response to antiretroviral therapy.

People with HCV genotypes other than 1, however, appeared to respond less well to HAART, significantly so for genotype 4.

"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.