Siblings of HIV/HCV coinfected patients also have higher mortality risk

Genetics and environmental factors may make an important contribution to the increased risk of mortality seen in individuals coinfected with HIV and hepatitis C virus (HCV), according to a study published in the January 15^th edition of the Journal of Infectious Diseases. Danish investigators looked at mortality amongst the siblings of individuals who were HIV/HCV coinfected and compared it with that seen in siblings of patients only infected with HIV and the general population. They found that the brothers and sisters of coinfected patients had a higher risk of mortality than both those of the HIV-monoinfected patients and controls. They therefore suggest that genetics and socioeconomic conditions may have an important role in the excess mortality seen in coinfected patients.

It is well known that individuals who are coinfected with HIV and hepatitis C virus (HCV) have a worse prognosis than individuals who are only infected with HIV. Although some of this excess mortality has been attributed to liver disease, there is no agreement about the role that other medical and social factors play.

Investigators from Denmark hypothesised that coinfection with HIV/HCV was an indicator of familial risk factors and that such familial factors would have an effect on survival independent of HCV. To test this theory, they compared mortality in three groups: the siblings of patients coinfected with HIV/HCV; the siblings of patients infected with HIV; and, the siblings of age and sex matched controls randomly selected from the general Danish population. The end points of the study were survival for 20 years (or until age 50), emigration, or the termination of the study in May 2005.

A total of 437 siblings of HIV/HCV-infected patients were identified, 1,856 siblings of patients who only had HIV, and over 285,000 siblings from the general Danish population. Mortality was significantly higher amongst the siblings of coinfected patients (MRR: 2.97), than the mortality risk seen amongst the siblings of HIV-infected patients (MRR: 4.23). The investigators also found that the siblings of patients who were only infected with HIV had a modestly increased risk of death compared to the siblings of the control population (MRR: 1.43).

In further analysis, the investigators restricted their analysis to the siblings of those coinfected patients who acquired HIV via unprotected sex. Once again, they found a significantly increased risk of death compared to both the siblings of HIV-monoinfected patients (MRR: 3.09) and the control siblings (MRR: 4.58). The investigators also established that the siblings of HIV-monoinfected patients who whose HIV risk activity was injecting drug use had higher mortality than both the siblings of HIV-infected individuals who did not report drug use (MRR: 2.60), or control siblings (mortality risk ratio: 4.19).

“We found markedly higher mortality among siblings of patients coinfected with HCV and HIV than among siblings of HIV-monoinfected patients or of control subjects”, comment the investigators.

They add, “the observed excess risk of death in siblings of HIV/HCV-coinfected individuals may be due to a combination of environmental and genetic factors.”

For example, “it has been well established that adverse socioeconomic conditions during childhood are associated with increased mortality during adulthood because they herald continued lower socioeconomic conditions or through direct effects of childhood environment on later life.”

Although it is coinfected patients shared injecting drug use habits with their brothers or sisters, leading to a shared risk of earlier death, the investigators do not believe that this alone can explain the findings of their study. They emphasise that the siblings of coinfected patients who acquired HIV because of unprotected sex also had increased mortality.

The investigators then turn their attention to genetics, and note that recent studies suggest that there may be a genetic predisposition to alcohol or drug use, and that this could also partly explain their findings.

Although a previous study found that HIV-positive individuals in Denmark were up to 15 times more likely to die than the general population, no evidence was found of an increase in the familial risk of death. “Thus, the contribution of socioeconomic or genetic factors in mortality in HIV-monoinfected patients appears to have little importance.”

The investigators did not gather data on the causes of death or HCV status of siblings and they acknowledge that these are “shortcomings” of their study. They conclude, “the higher mortality observed in siblings of HIV/HCV-coinfected patients suggests that familial factors are involved in HCV-related mortality among HIV-infected patients. Differences in family background and socioeconomic factors may explain part, if not all, of the reported interstudy differences regarding the impact of HCV on mortality among HIV-infected patients. Studies that fail to account for these factors may overestimate the mortality attributable to HCV infection.”