Characteristics of non-Hodgkin lymphoma arising in HIV-infected patients with suppressed HIV replication

Objective:Despite effective treatment of HIV infection, some patients still develop non-Hodgkin lymphoma (NHL). We analysed patients with HIV-associated NHL and undetectable plasma HIV-RNA, according to the duration of HIV suppression. Methods:Out of 388 patients included in a prospective cohort of HIV-associated NHL from 1996 to 2008, 128 (33%) had a plasma HIV-RNA below 500 copies/ml and were included in the study. Patients with long-term HIV suppression (>18 months) were compared with patients with recent HIV suppression (≤18 months). Results:All patients but three were treated with combination antiretroviral therapy, with a median duration of 2.2 years. The median duration of HIV suppression was 10.1 months. Most cases (65%) occurred within 18 months following HIV suppression. In the more than 18 months group, patients developed NHL at a higher CD4 cell count than patients with 18 months or less of HIV suppression (359 versus 270 cells/μl, P = 0.02). None of the NHL characteristics were different between the two groups. Outcome was similar in the two groups (complete remission, 64 versus 72.5%; P = 0.35 and 3-year survival, 46 versus 56%; P = 0.08). In addition, 52% of the tumours were Epstein–Barr virus or human herpesvirus 8 associated, without any difference in the proportion of virus-associated tumours according to the duration of HIV suppression. Conclusion:In patients with undetectable HIV-RNA, NHL occurred mainly within the first 18 months following HIV suppression. In patients developing NHL after long-term HIV suppression, the level of CD4 cell count was higher, but the association with Epstein–Barr virus or human herpesvirus 8 and the prognosis were similar to that observed in patients with recent HIV suppression.

[1]  K. H. Hullsiek,et al.  Trends in the incidence of cancers among HIV-infected persons and the impact of antiretroviral therapy: a 20-year cohort study , 2009, AIDS.

[2]  O. Kirk,et al.  HIV-induced immunodeficiency and mortality from AIDS-defining and non-AIDS-defining malignancies , 2008, AIDS.

[3]  P. Morlat,et al.  Changes in Causes of Death Among Adults Infected by HIV Between 2000 and 2005: The “Mortalité 2000 and 2005” Surveys (ANRS EN19 and Mortavic) , 2008, Journal of acquired immune deficiency syndromes.

[4]  P. Sullivan,et al.  Incidence of types of cancer among HIV-infected persons compared with the general population in the United States, 1992-2003. , 2008, Annals of internal medicine.

[5]  A. Carbone,et al.  KSHV/HHV8‐associated lymphomas , 2007, British journal of haematology.

[6]  M. Falster,et al.  Incidence of cancers in people with HIV/AIDS compared with immunosuppressed transplant recipients: a meta-analysis , 2007, The Lancet.

[7]  J. Kaldor,et al.  Cancer incidence before and after kidney transplantation. , 2006, JAMA.

[8]  J. Goedert,et al.  Trends in cancer risk among people with AIDS in the United States 1980–2002 , 2006, AIDS.

[9]  John P. Moore,et al.  HIV-1 Envelope Triggers Polyclonal Ig Class Switch Recombination through a CD40-Independent Mechanism Involving BAFF and C-Type Lectin Receptors1 , 2006, The Journal of Immunology.

[10]  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.

[11]  B. Nathwani,et al.  Prognostic factors in HIV-related diffuse large-cell lymphoma: before versus after highly active antiretroviral therapy. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[12]  B. Nathwani,et al.  AIDS-related Burkitt's lymphoma versus diffuse large-cell lymphoma in the pre-highly active antiretroviral therapy (HAART) and HAART eras: significant differences in survival with standard chemotherapy. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[13]  E. Cesarman,et al.  KSHV-Positive Solid Lymphomas Represent an Extra-Cavitary Variant of Primary Effusion Lymphoma , 2004, The American journal of surgical pathology.

[14]  U. Siebert,et al.  Response to highly active antiretroviral therapy strongly predicts outcome in patients with AIDS-related lymphoma , 2003, AIDS.

[15]  J. Goedert,et al.  Immunoblastic Lymphoma in Persons with AIDS-Associated Kaposi's Sarcoma: a Role for Kaposi's Sarcoma–Associated Herpesvirus , 2003, Modern Pathology.

[16]  É. Oksenhendler,et al.  Systemic Non‐Hodgkin Lymphoma in HIV‐Infected Patients With Effective Suppression of HIV Replication: Persistent Occurrence But Improved Survival , 2002, Journal of acquired immune deficiency syndromes.

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

[18]  C. Katlama,et al.  Changes in AIDS-related lymphoma since the era of highly active antiretroviral therapy. , 2001, Blood.

[19]  R. Ambinder Epstein-Barr virus associated lymphoproliferations in the AIDS setting. , 2001, European journal of cancer.

[20]  B. Nathwani,et al.  Evolving characteristics of AIDS-related lymphoma. , 2000, Blood.

[21]  S. Franceschi,et al.  Epidemiological, biological and clinical features of HIV-related lymphomas in the era of highly active antiretroviral therapy. , 2000, AIDS.

[22]  A. Mocroft,et al.  AIDS across Europe, 1994–98: the EuroSIDA study , 2000, The Lancet.

[23]  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.

[24]  A. Telenti,et al.  Risk of HIV related Kaposi's sarcoma and non-Hodgkin's lymphoma with potent antiretroviral therapy: prospective cohort study , 1999, BMJ.

[25]  JD Lundgren,et al.  Changing patterns of mortality across Europe in patients infected with HIV-1 , 1998, The Lancet.

[26]  M. Testa,et al.  Prognostic factors in the treatment of human immunodeficiency virus-associated non-Hodgkin's lymphoma: analysis of AIDS Clinical Trials Group protocol 142--low-dose versus standard-dose m-BACOD plus granulocyte-macrophage colony-stimulating factor. National Institute of Allergy and Infectious Diseas , 1998, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[27]  P. Kissinger,et al.  Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. , 1998, The New England journal of medicine.

[28]  G. Satten,et al.  Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. HIV Outpatient Study Investigators. , 1998, The New England journal of medicine.

[29]  Manuel Battegay,et al.  Impact of new antiretroviral combination therapies in HIV infected patients in Switzerland: prospective multicentre study , 1997, BMJ.

[30]  E. Cesarman,et al.  Primary effusion lymphoma: a distinct clinicopathologic entity associated with the Kaposi's sarcoma-associated herpes virus. , 1996, Blood.

[31]  E. Cesarman,et al.  Kaposi's sarcoma-associated herpesvirus-like DNA sequences in AIDS-related body-cavity-based lymphomas. , 1995, The New England journal of medicine.

[32]  Emili Montserrat,et al.  A predictive model for aggressive non-Hodgkin's lymphoma. , 1993, The New England journal of medicine.

[33]  D. Venzon,et al.  Parameters affecting the development of non-Hodgkin's lymphoma in patients with severe human immunodeficiency virus infection receiving antiretroviral therapy. , 1993, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[34]  D. Weisenburger,et al.  Lymphoma incidence patterns by WHO subtype in the United States, 1992-2001. , 2006, Blood.

[35]  H. Anton-Culver,et al.  Changes in acquired immunodeficiency syndrome‐related non‐Hodgkin lymphoma in the era of highly active antiretroviral therapy , 2006, Cancer.

[36]  A. Carbone Emerging pathways in the development of AIDS-related lymphomas. , 2003, The Lancet. Oncology.

[37]  D. Straus Prognostic factors in the treatment of human immunodeficiency virus-associated non-Hodgkin's lymphoma. , 2002, Recent results in cancer research. Fortschritte der Krebsforschung. Progres dans les recherches sur le cancer.