Risk for Non-Hodgkin Lymphoma in HIV-Infected Patients

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In the HIV-negative population, there is growing evidence suggesting that chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) are both associated with the development of non-Hodgkin lymphoma (NHL), although the mechanisms underlying this association remain unclear. The incidence rate of NHL in HIV-infected individuals is about 10 times higher than that in HIV-negative individuals and is an important cause of AIDS and death, even for people receiving antiretroviral therapy. Growing evidence suggests that some infections increase the risk for NHL through chronic immune stimulation, which occurs in immunocompromised patients.

Now a large prospective cohort study by Qing Wang, PhD, and colleagues, on behalf of the Hepatitis Coinfection and Non-Hodgkin Lymphoma project team for the Collaboration of Observational HIV Epidemiological Research Europe (COHERE), investigated whether HBV and HCV infection promotes NHL in HIV-infected patients receiving antiretroviral therapy. The investigators found that these patients were at increased risk for NHL compared with uninfected persons. Early diagnosis and treatment of HIV infection in conjunction with routine screening for chronic HBV and HCV infection are crucial in decreasing NHL morbidity and mortality in HIV-infected patients, concluded the investigators. The study was published in the Annals of Internal Medicine.

The researchers analyzed data from 18 of 33 cohorts from COHERE. The data collected included information on patient characteristics, antiretroviral therapy, CD4 cell count, HIV RNA viral load, co-infection with HBV or HCV, AIDS events, and causes of death. The patients were analyzed in two separate periods: while they were naive to antiretroviral therapy and during receipt of antiretroviral therapy.

Time-dependent Cox models were used to assess the risk for NHL in both treatment-naive patients and patients receiving antiretroviral therapy to estimate hazard ratios and corresponding 95% confidence intervals (CIs) for the association between chronic HBV and HCV infection and the risk for NHL in these patients.

Study Findings

A total of 52,479 treatment-naive patients (1,339 [2.6%] with chronic HBV infection and 7,506 [14.3%] with HCV infection) were included in this study, of whom 40,219 (77%) later started antiretroviral therapy. The median follow-up was 13 months for treatment-naive patients and 50 months for those receiving antiretroviral therapy.

A total of 252 treatment-naive patients and 310 treated patients developed NHL, with incidence rates of 219 and 168 cases per 100,000 person-years, respectively. The hazard ratios for NHL with HBV and HCV infection were 1.33 (95% CI = 0.69–2.56) and 0.67 (95% CI = 0.40–1.12), respectively, in treatment-naive patients and 1.74 (95% CI = 1.08–2.82) and 1.73 (95% CI = 1.21–2.46), respectively, in treated patients.

“[Antiretroviral therapy]-treated patients with chronic HBV and HCV co-infection are at increased risk for NHL, which is the most frequently occurring AIDS-defining condition. Our study was not sufficiently powered to show such an association in [antiretroviral therapy]-naive co-infected patients. Early diagnosis and treatment of HIV infection in conjunction with routine screening for chronic HBV and HCV infection are essential to further decrease NHL morbidity and mortality in HIV-infected persons,” concluded the study authors.

Funding for this study was provided by the European Union Seventh Framework Programme and Schweizerische Krebsliga. Funding of the COHERE study group was provided by the Agence Nationale de Recherches sur le SIDA et les Hépatites Virales, the HIV Monitoring Foundation, and the Augustinus Foundation

Wang Q, et al: Ann Intern Med. October 18, 2016 (early release online).