A high level of hepatitis C virus (HCV) in the blood is associated with an increased risk of death in HIV/HCV co-infected individuals, according to data presented on February 10th at the Sixteenth Conference on Retroviruses and Opportunistic Infections in Montreal, Canada.
Jürgen Rockstroh from the University of Bonn, Germany, presented results from a study evaluating the influence of HCV viral load and genotype on disease progression and response to antiretroviral therapy amongst all HIV/HCV co-infected participants in EuroSIDA, a prospective observational cohort of more than 16,000 HIV-positive individuals from more than 30, mostly European, countries.
Having previously shown that being HCV antibody-positive was not associated with increased mortality amongst people with HIV, the investigators looked at rates of death due to any cause and due to liver-related disease, comparing co-infected people with high (500,000 IU/ml or more), low (less than 500,000 IU/ml) and undetectable (less that 615 IU/ml) HCV viral load, and those with HCV genotypes 1, 2, 3 and 4.
Out of 1952 identified HIV/HCV coinfected cohort members, 821 (42%) fell into the high HCV viral load group, 716 (37%) fell into the low HCV group, and 415 (21%) had undetectable HCV. Amongst the 1537 participants with measurable HCV, just over half had hard-to-treat genotype 1, nearly one-third had genotype 3, about 14% had genotype 4 and only 3% had genotype 2. Very few (about 2%) had taken interferon-based therapy for hepatitis C, though the numbers increased over time.
A total of 78 people in the undetectable HCV viral load group died due to any cause, compared with 96 in the low HCV group and 158 in the high HCV group. All-cause mortality rates for the three groups were 3.12, 1.74, and 4.17 per 100 person-years, respectively.
A similar pattern was seen for deaths due to liver disease, though the numbers were smaller: 17 people in the undetectable HCV group died due to liver-related causes, compared with 32 in the low HCV group and 49 in the high HCV group, translating to rates of 0.68, 0.58, and 1.29 deaths per 100 person-years, respectively.
After adjusting for potential confounding factors including sex, age, race/ethnicity, HIV transmission risk group, immune status (CD4 cell count and history of AIDS diagnosis), type of antiretroviral therapy, region of Europe, and triple infection with hepatitis B, it was found that people with undetectable and low HCV viral load had similar rates of death due to any cause, but the rate was nearly doubled in the high HCV group (adjusted incidence rate ratio of 1.94).
Restricting the adjusted analysis to liver-related deaths, people with undetectable and low HCV viral load again had statistically similar liver-related mortality rates, whilst those in the high HCV group were 77% more likely than to die of such cause than those in the low viral load group (adjusted incidence rate ratio of 1.77).
After adjustment, people with HCV genotypes 2 and 3 had a lower rate of all-cause death than those with genotype 1, but this was only significant for genotype 3. A similar pattern was seen for liver-related deaths, but differences did not reach statistical significance, possibly due to small numbers. This finding is noteworthy because HCV genotype 3 is associated with liver steatosis (fat accumulation), which might be expected to predict worse outcomes.
In addition, Dr Rockstroh reported that HCV viral load level was not correlated with differences in response to antiretroviral therapy, either HIV suppression or CD4 cell recovery. However, people with HCV genotypes other than 1 had poorer virological and immunological response to anti-HIV therapy, reaching statistical significance for genotype 4 – a finding he said has not been observed in HIV-negative hepatitis C patients.
These findings prompted some debate, as prior research in HIV-negative people with hepatitis C has not revealed a link between HCV viral load or genotype and liver disease progression.
Dr Rockstroh acknowledged that mortality rates were not adjusted for fibrosis stage in this analysis, as this information was not generally available (it is now being collected). Assessment of alcohol use, he added, is "extremely difficult" in this type of observational study.
In closing, Dr Rockstroh suggested that the effect of HCV viral load on mortality may be more apparent in HIV-positive individuals, who tend to have higher HCV RNA levels and more rapid liver disease progression than HIV-negative hepatitis C patients.
Rockstroh J et al. High HCV is associated with an increased risk for mortality in HIV/HCV-co-infected individuals. Sixteenth Conference on Retroviruses and Opportunistic Infections, Montreal, abstract 101, 2009.