Despite the benefits of HAART, HIV-infected patients are increasingly affected by different malignancies. We compared a 5-year-period survival time and prognostic factors for HIV-1-infected individuals diagnosed with non-Hodgkin lymphomas (NHL) in a nested case-control study, with non-HIV-infected individuals in Salvador, Brazil. Survival time and prognostic factors were compared to HIV-negative patients. 31 cases (versus 63 controls) had a significantly more advanced NHL at diagnosis and lower mean CD4 count (26？cells/mm3) than controls. Mean overall survival (OS) was 35.8 versus 75.4 months, for cases and controls, respectively ( ), while mean event-free survival time (EFS) was 34.5 months for cases, versus 68.8 for controls ( ). Higher IPI, increased LDH levels, bone marrow infiltration, lower absolute lymphocyte counts (<1,000？cells/mm3), and type B symptoms were associated with a shorter survival time for cases. Although patients without poorer prognostic factors at baseline had an OS comparable to controls, the mean CD4 cell count for cases was similar for patients with favorable and nonfavorable response to therapy. Our findings suggest that HIV-1 infection is significantly associated with a shorter survival time for patients with NHL, independently of other predictive factors and of disease stage. 1. Introduction The main characteristic of AIDS is a severe immunodeficiency caused by the progressive depletion of CD4+ T-cells and consequent immune impairment [1]. These facts ultimately lead to an increasing risk of developing opportunistic infections and malignancies [2, 3]. Non-Hodgkin lymphoma (NHL) is an AIDS-defining condition, and its frequency seems to be decreasing after the highly active antiretroviral therapy (HAART) became the standard of care for the management of AIDS patients [4, 5]. HAART has promoted a great increase in the lifespan of HIV-infected patients and decreased the morbidity and mortality caused by AIDS [6]. However, the available evidence suggests that around half of the patients treated are unable to reach a normal CD4+ cell count, even after years of persistent viral suppression. One of the reasons for such findings is the persistent immune activation, but its causative mechanisms are still a matter of debate [7]. These facts may be responsible for the persistence of a higher risk for the development of other malignancies, a trend recently detected in treated AIDS patients, as a likely consequence of incomplete immune restoration. While there is a clear trend toward reducing AIDS-defining events (which include Kaposi’s
References
[1]
A. N. Phillips, M. Youle, F. Lampe et al., “CD4 cell count changes in individuals with counts above 500 cells/mm3 and viral loads below 50 copies/mL on antiretroviral therapy,” AIDS, vol. 16, no. 7, pp. 1073–1075, 2002.
[2]
L. Gil, G. Martínez, I. González et al., “Contribution to characterization of oxidative stress in HIV/AIDS patients,” Pharmacological Research, vol. 47, pp. 217–224, 2003.
[3]
C. Smith, S. Lilly, K. P. Mann et al., “AIDS-related malignancies,” Annals of Medicine, vol. 30, no. 4, pp. 323–344, 1998.
[4]
A. Grulich, X. Wan, M. Law, M. Coates, and M. Kaldor, “Risk of cancer in people with aids,” AIDS, vol. 13, no. 7, pp. 839–843, 1999.
[5]
C. Wood and W. Harrington Jr., “AIDS and associated malignancies,” Cell Research, vol. 15, no. 11-12, pp. 947–952, 2005.
[6]
M. W. Otieno, C. Banura, E. Katongole-Mbidde et al., “Therapeutic challenges of AIDS-related non-Hodgkin's lymphoma in the United States and East Africa—a review,” Journal of the National Cancer Institute, vol. 94, no. 10, pp. 718–732, 2002.
[7]
A. M. Levine, “Acquired immunodeficiency syndrome-related lymphoma: clinical aspects,” Seminars in Oncology, vol. 27, no. 4, pp. 442–453, 2000.
[8]
E. A. Engels, R. M. Pfeiffer, J. J. Goedert et al., “Trends in cancer risk among people with AIDS in the United States 1980–2002,” AIDS, vol. 20, no. 12, pp. 1645–1654, 2006.
[9]
J. L. Long, E. A. Engels, R. D. Moore, and K. A. Gebo, “Incidence and outcomes of malignancy in the HAART era in an urban cohort of HIV-infected individuals,” AIDS, vol. 22, no. 4, pp. 489–496, 2008.
[10]
R. J. Bedimo, K. A. McGinnis, M. Dunlap, M. C. Rodriguez-Barradas, and A. C. Justice, “Incidence of non-AIDS-defining malignancies in HIV-infected versus noninfected patients in the HAART era: impact of immunosuppression,” Journal of Acquired Immune Deficiency Syndromes, vol. 52, no. 2, pp. 203–208, 2009.
[11]
C. Wood and W. Harrington Jr., “AIDS and associated malignancies,” Cell Research, vol. 15, no. 11-12, pp. 947–952, 2005.
[12]
O. C. Baiocchi, G. W. Colleoni, E. V. Navajas et al., “Impact of highly active antiretroviral therapy in the treatment of HIV-infected patients with systemic non-Hodgkin's lymphoma,” Acta Oncologica, vol. 41, no. 2, pp. 192–196, 2002.
[13]
J. R. Marins, L. F. Jamal, S. Y. Chen et al., “Dramatic improvement in survival among adult Brazilian AIDS patients,” AIDS, vol. 17, no. 11, pp. 1675–1682, 2003.
[14]
S. Rosenberg, “Validity of the Ann Arbor staging classification for the non-Hodgkin's lymphomas,” Cancer Treatment Reports, vol. 61, no. 6, pp. 1023–1027, 1977.
[15]
M. M. Oken, R. H. Creech, D. C. Tormey et al., “Toxicity and response criteria of the Eastern Cooperative Oncology Group,” The American Journal of Clinical Oncology, vol. 5, pp. 649–655, 1982.
[16]
“A predictive model for aggressive non-Hodgkin's lymphoma. The International Non-Hodgkin's Lymphoma Prognostic Factors Project,” The New England Journal of Medicine, vol. 329, pp. 987–994, 1993.
[17]
C. S. Rabkin and F. Yellin, “Cancer incidence in a population with a high prevalence of infection with human immunodeficiency virus type 1,” Journal of the National Cancer Institute, vol. 86, no. 22, pp. 1711–1716, 1994.
[18]
B. Kiely, J. O'Flaherty, S. Surah et al., “HIV-related malignancies pre- and post-highly active antiretroviral therapy: experiences in an inner city tertiary referral centre,” International Journal of STD and AIDS, vol. 21, no. 5, pp. 332–336, 2010.
[19]
J. Pereira, A. E. Hallack Neto, L. F. Pracchia et al., “Quimioterapia associada à terapia anti-retroviral de alta eficácia no tratamento dos linfomas n？o-Hodgkin agressivos relacionados à Síndrome da Imunodeficiência Adquirida,” Revista Brasileira de Hematologia e Hemoterapia, vol. 26, pp. 177–182, 2004.
[20]
L. Barreto, D. Azambuja, and J. C. de Morais, “Expression of immunohistochemical markers in patients with AIDS-related lymphoma,” The Brazilian Journal of Infectious Diseases, vol. 16, no. 1, pp. 74–77, 2012.
[21]
M. Simcock, M. Blasko, U. Karrer et al., “Treatment and prognosis of AIDS-related lymphoma in the era of highly active antiretroviral therapy: findings from the Swiss HIV Cohort Study,” Antiviral Therapy, vol. 12, no. 6, pp. 931–939, 2007.
[22]
M. Moreira, A. Ramos, E. M. Netto, and C. Brites, “Characteristics of co-infections by HCV and HBV among Brazilian patients infected by HIV-1 and/or HTLV-1,” The Brazilian Journal of Infectious Diseases, 2013.
[23]
D. H. Kim, J. H. Baek, Y. S. Chae et al., “Absolute lymphocyte counts predicts response to chemotherapy and survival in diffuse large B-cell lymphoma,” Leukemia, vol. 21, no. 10, pp. 2227–2230, 2007.
[24]
R. Kim, M. Emi, K. Tanabe, and K. Arihiro, “Tumor-driven evolution of immunosuppressive networks during malignant progression,” Cancer Research, vol. 66, no. 11, pp. 5527–5536, 2006.
[25]
C. Choi, H. Sung, K. Park et al., “Early lymphopenia as a risk factor for chemotherapy-induced febrile neutropenia,” The American Journal of Hematology, vol. 73, no. 4, pp. 263–266, 2003.
[26]
I. Ray-Coquard, C. Borg, T. Bachelot et al., “Baseline and early lymphopenia predict for the risk of febrile neutropenia after chemotherapy,” The British Journal of Cancer, vol. 88, no. 2, pp. 181–186, 2003.
