Interleukine-2 Therapy Does Not Increase the Risk of Hodgkin or Non-Hodgkin Lymphoma in HIV-Infected Patients: Results From FHDH ANRS CO4

Background:Concerns have been raised about a possible excess risk of lymphomas in HIV-infected patients exposed to interleukin 2 (IL-2) therapy. Here we compared the risks of non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL) in IL-2-treated and IL-2-untreated HIV-infected patients. Methods:Patients monitored through the French Hospital Database on HIV between May 1, 1995, and December 31, 2005, were enrolled in this study. Lymphomas that occurred between the day after study entry and the end of follow-up were eligible for analysis. Poisson regression models were used in 2 separate analyses to quantify the possible relationship between IL-2 therapy and the incidence of NHL and HL. Results:The IL-2-treated group consisted of 861 patients and the IL-2-untreated group of 77,605 patients. Follow-up lasted a total of 3643 and 382,720 person-years, respectively. After adjustment for sex and time-updated age, period, the CD4 cell counts, the plasma HIV RNA levels, and AIDS status, the relative rates of NHL and HL associated with IL-2 therapy were 0.64 (95% confidence interval, 0.25 to 1.65) and 0.33 (95% confidence interval, 0.04 to 2.86), respectively. Conclusions:In this large observational study, IL-2 therapy did not increase the risk of lymphoma, either NHL or HL, in HIV-infected patients.

[1]  A. Pathak,et al.  Vascular Health and Risk Management Dovepress Eprosartan-based Hypertension Therapy, Systolic Arterial Blood Pressure and Cognitive Function: Analysis of Middle East Data from the Oscar Study , 2022 .

[2]  E. Engels.  Infectious Agents as Causes of Non-Hodgkin Lymphoma , 2007, Cancer Epidemiology Biomarkers & Prevention.

[3]  P. Boffetta,et al.  Occupation and the Risk of Non-Hodgkin Lymphoma , 2007, Cancer Epidemiology Biomarkers & Prevention.

[4]  C. Skibola.  Obesity, Diet and Risk of Non-Hodgkin Lymphoma , 2007, Cancer Epidemiology Biomarkers & Prevention.

[5]  P. Hartge,et al.  Environmental and Behavioral Factors and the Risk of Non-Hodgkin Lymphoma , 2007, Cancer Epidemiology Biomarkers & Prevention.

[6]  D. Weisenburger,et al.  Family history of hematopoietic malignancies and risk of non-Hodgkin lymphoma (NHL): a pooled analysis of 10 211 cases and 11 905 controls from the International Lymphoma Epidemiology Consortium (InterLymph). , 2006, Blood.

[7]  J. Goedert,et al.  Hodgkin lymphoma and immunodeficiency in persons with HIV/AIDS. , 2006, Blood.

[8]  N. Probst-Hensch,et al.  Hepatitis C virus and non-Hodgkin's lymphoma: findings from the Swiss HIV Cohort Study , 2006, British Journal of Cancer.

[9]  R. Davey,et al.  Reporting and Evaluation of HIV-Related Clinical Endpoints in Two Multicenter International Clinical Trials , 2006, HIV clinical trials.

[10]  C. Hallahan,et al.  Interruption of antiretroviral therapy blunts but does not abrogate CD4 T-cell responses to interleukin-2 administration in HIV infected patients , 2006, AIDS.

[11]  D. Neau,et al.  Factors associated with the occurrence of AIDS-related non-Hodgkin lymphoma in the era of highly active antiretroviral therapy: Aquitaine Cohort, France. , 2006, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[12]  Y. Lévy.  Cytokine-based modulation of immune function in HIV infection , 2006, Current opinion in HIV and AIDS.

[13]  G. Marchetti,et al.  Partial immune reconstitution following highly active antiretroviral therapy: can adjuvant interleukin-2 fill the gap? , 2005, The Journal of antimicrobial chemotherapy.

[14]  Olivia Keiser,et al.  Cancer risk in the Swiss HIV Cohort Study: associations with immunodeficiency, smoking, and highly active antiretroviral therapy. , 2005, Journal of the National Cancer Institute.

[15]  J. Kaldor,et al.  Sun exposure may protect against non‐Hodgkin lymphoma: A case‐control study , 2004, International journal of cancer.

[16]  R. Davey,et al.  CD4 cell response to 3 doses of subcutaneous interleukin 2: meta-analysis of 3 Vanguard studies. , 2004, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[17]  D. Follmann,et al.  Induction and maintenance therapy with intermittent interleukin-2 in HIV-1 infection. , 2004, Blood.

[18]  N. Rothman,et al.  Diet and nutrient intakes and risk of non-Hodgkin's lymphoma in Connecticut women. , 2004, American journal of epidemiology.

[19]  D. Costagliola,et al.  Incidence of non-AIDS-defining cancers before and during the highly active antiretroviral therapy era in a cohort of human immunodeficiency virus-infected patients. , 2003, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[20]  É. Oksenhendler,et al.  Effects of interleukin-2 therapy combined with highly active antiretroviral therapy on immune restoration in HIV-1 infection: a randomized controlled trial , 2003, AIDS.

[21]  V. Calvez,et al.  Interleukin-2 accelerates CD4 cell reconstitution in HIV-infected patients with severe immunosuppression despite highly active antiretroviral therapy: the ILSTIM study – ANRS 082 , 2002, AIDS.

[22]  A. Lazzarin,et al.  Retrospective analysis of HHV-8 viremia and cellular viral load in HIV-seropositive patients receiving interleukin 2 in combination with antiretroviral therapy. , 2002, Blood.

[23]  J. Kaldor,et al.  Rates of non-AIDS-defining cancers in people with HIV infection before and after AIDS diagnosis , 2002, AIDS.

[24]  O. Kirk,et al.  Non-Hodgkin lymphoma in HIV-infected patients in the era of highly active antiretroviral therapy. , 2001, Blood.

[25]  C. Rouzioux,et al.  Immunological and virological effects of long term IL-2 therapy in HIV-1-infected patients. , 2001, AIDS.

[26]  J. Goedert,et al.  Association of cancer with AIDS-related immunosuppression in adults. , 2001, JAMA.

[27]  J. Kahn,et al.  Immunologic and virologic effects of subcutaneous interleukin 2 in combination with antiretroviral therapy: A randomized controlled trial. , 2000, JAMA.

[28]  J. Kaldor,et al.  B-cell stimulation and prolonged immune deficiency are risk factors for non-Hodgkin's lymphoma in people with AIDS , 2000, AIDS.

[29]  É. Oksenhendler,et al.  Comparison of subcutaneous and intravenous interleukin-2 in asymptomatic HIV-1 infection: a randomised controlled trial , 1999, The Lancet.

[30]  R. Dewar,et al.  A randomized trial of high- versus low-dose subcutaneous interleukin-2 outpatient therapy for early human immunodeficiency virus type 1 infection. , 1999, The Journal of infectious diseases.

[31]  J. Metcalf,et al.  Controlled trial of interleukin-2 infusions in patients infected with the human immunodeficiency virus. , 1996, The New England journal of medicine.

[32]  D. Federman,et al.  The epidemiology of non-Hodgkin's lymphoma. , 1996, Connecticut medicine.

[33]  M. T. Paixão,et al.  Expanded European AIDS case definition , 1993, The Lancet.

[34]  Kendall A. Smith,et al.  Interleukin-2: inception, impact, and implications. , 1988, Science.

[35]  John McGrath,et al.  Hodgkin’s Disease , 1933, JAMA.

[36]  S Greenland,et al.  The impact of confounder selection criteria on effect estimation. , 1989, American journal of epidemiology.