Research indicates that, with shared risk factors, hepatitis C virus (HCV) and hepatitis B virus (HBV) often co-infect people living with HIV (PLHIV). Studies also suggest that risk for lymphoma is increased in patients with each of these infections. Prior to the wide availability of combined antiretroviral therapy (cART) for PLHIV, lymphoma risk was largely driven by HIV-induced immune deficiency, explains Caroline Besson, MD, PhD. “Since cART is largely available and efficient in restoring immunity, the mechanisms leading to lymphoma in PLHIV has changed,” she adds. “Instead of immune deficiency, immune activation is thought to play an important role in lymphomagenesis. In this context, studying the impact of coinfections with agents known to induce, per se, immune stimulation and lymphoma is important.”

Assessing Associations

For a study published in AIDS, Dr. Besson and colleagues assessed data from a cohort of PLHIV with lymphoma and a cohort of PLHIV without lymphoma. “We analyzed the two cohorts to compare the prevalence of chronic HCV and/or HBV infection in individuals with lymphoma and HIV with that of those with HIV but without lymphoma,” notes Dr. Besson. “We also described, within the lymphoma cohort, the characteristics of the patients with lymphoma and HBV or HCV coinfection.” Among participants with HIV-related lymphomas, 39% had Hodgkin’s lymphoma and 61% had non-Hodgkin’s lymphoma (NHL).

“Chronic HCV infection in patients with HIV doubled the risk of NHL,” says Dr. Besson (Table). Indeed, when compared with participants without lymphoma, those with NHL had an odds ratio of 2.15 for the prevalence of HCV infection. In fact, risk for diffuse large B-cell lymphoma—the most prominent type of NHL in PLHIV—was nearly tripled in patients chronically co-infected with HCV. However, no association was observed between Hodgkin’s lymphoma and chronic HCV infection. Chronic HCV infection also tended to pejoratively impact 2-year overall survival, with rates of 72% in those with HCV and NHL and 82% in those without HCV (Figure).

While chronic HBV infection was found to not be associated with NHL—with prevalence rates of 5% in PLHIV with lymphoma and 7% in PLHIV without lymphoma—it tended to be associated with Hodgkin’s lymphoma, with an odds ratio of 2.16. “This finding may be linked to different characteristics of patients with classical Hodgkin’s lymphoma, like a long history of HIV infection from a period when HBV chronic infections were not always treated in PLHIV,” adds Dr. Besson. Chronic HBV infection was not correlated with outcomes in the study population.

Reflecting on the Findings

Dr. Besson notes the desire for future research showing that the prevalence of chronic HCV infection decreases in HIV-infected individuals and leads to a decrease of the lymphoma incidence now that direct antiviral agents have been shown to be very efficient against HCV. In the meantime, she says her study findings “further support the prescription of active treatment of HCV and HBV infections in all PLHIV with these chronic infections, even in the absence of liver disease, as this would probably decrease the risk of lymphoma.”