Use of rituximab for treatment of HIV-infected patients with hematological disorders

A.V. Pivnik

Medical Center «Genotehnology», Moscow, Russian Federation


Rituximab (MabThera) is one of the most powerful drug with selective action on B-cells. The drug suppresses the polyclonal antibody response to own antigens in autoimmune diseases. For lymphatic tumors it selectively acts on tumors of B-cells. Rituximab is widely used in the treatment of patients with immune thrombocytopenic purpura, Moshkovich thrombotic thrombocytopenic purpura, autoimmune hemolytic anemia, rheumatoid arthritis, systemic lupus erythematosus, Crohn’s disease and other diseases. This review describes the clinical cases with the mentioned diseases. All of them are infected with HIV at different stages of the disease. The efficacy of the drug and moderate toxicity were illustrated. Indicators of  HIV infection (CD4 count and viral load) were independent of the drug. In general, rituximab demonstrated successful assessment in hematologic HIV-infected patients.

Keywords: rituximab and HIV, ITP, AIHA, TTP, lymphomas in HIV-infected patients.

Read in PDF (RUS)pdficon


  1. Ермак Т.Н., Кравченко А.В., Шахгильдян В.И. Анализ причин летальных исходов больных ВИЧ-инфекцией в Российской Федерации. Инфек. бол. 2010; 3: 19–20. [Ermak T.N., Kravchenko A.V., Shakhgil’dyan V.I. Analiz prichin letal’nykh iskhodov bol’nykh VICh-infektsiei v Rossiiskoi Federatsii (Analysis of causes of death in patients with HIV infection in the Russian Federation). Infek. bol. 2010; 3: 19–20.]
  2. Покровский В.В., Ермак Т.Н., Беляева В.В., Юрин О.Г. ВИЧ-инфекция. Клиника, диагностика, лечение. Под ред. В.В. Покровского, 2-е изд. М.: ГЭОТАР-Медиа, 2003. [Pokrovskii V.V., Ermak T.N., Belyaeva V.V., Yurin O.G. VICh-infektsiya. Klinika, diagnostika, lechenie. Pod red. V. Pokrovskogo, 2-e izd. (HIV infection. Clinical presentation, diagnostics, treatment. Ed. by V.V. Pokrovskii, 2nd ed.). M.: GEOTAR-Media, 2003.]
  3. Покровский В.В. Заболеваемость ВИЧ-инфекцией в Федеральных округах России на конец 2008 г. Эпидемиол. и инфек. бол. 2009; 6: 15–7. [Pokrovskii V.V. Zabolevaemost’ VICh-infektsiei v Federal’nykh okrugakh Rossii na konets 2008 g. (HIV infection incidence in the Federal regions of Russia by the end of 2008). i infek. bol. 2009; 6: 15–7.]
  4. http://data unaids.Org/publication/RC-publication/RC-pub06/jc1038-changingepidemic_en.pdf. The changing HIV/AIDS epidemic in Europe and Central Asia. 2004.
  5. Покровский В.В. Распределение ВИЧ-инфицированных по основным путям заражения на территории г. Москвы за период с 2000 по 2008 г. Эпидемиол. и инфек. бол. 2009; 8: 12–4. [Pokrovskii V.V. Raspredelenie VICh-infitsirovannykh po osnovnym putyam zarazheniya na territorii g. Moskvy za period s 2000 po 2008 g. (Distribution of HIV infection patients according to main modes of HIV transmission within the area of Moscow from 2000 to 2008). Epidemiol. i infek. bol. 2009; 8: 12–4.]
  6. Тишкевич О.А., Шахгильдян В.И., Пархоменко Ю.Г. Структура летальных исходов и патологчиеская анатомия у больных ВИЧ-инфекцией в Москве. Эпидемиол. и инфек. бол. 2004; 4: 42–6. [Tishkevich O.A., Shakhgil’dyan V.I., Parkhomenko Yu.G. Struktura letal’nykh iskhodov i patologchieskaya anatomiya u bol’nykh VICh-infektsiei v Moskve (Mortality pattern and pathologic anatomy in HIV infection patients). Epidemiol. i infek. bol. 2004; 4: 42–6.]
  7. Barcellini W., Zaja F., Zaninoni et al. Low-Dose Rituximab In Idiopathic Autoimmune Hemolytic Anemia: Biological Studies. Blood (ASH Annual Meeting Abstracts) 2010; 116: Abstract 3206.
  8. Ratner L. HIV-1 associated thrombocytopenia. In: Aids Clinical Treatment Group Meeting, Washington, July 1988, pp 13–15.
  9. Schneider P.A., Abrams D.I., Rayner A.A., Hohn D.C. Immunodeficiency associated thrombocytopenic purpura (IDTP). Surg. 1987; 122: 1175–8.
  10. Giagounidis A.A., Anhuf J., Schneider P. et al. Treatment of relapsed idiopathic thrombocytopenic purpura with the anti-CD20 monoclonal antibody rituximab: a pilot study. Eur. J. Haematol. 2002; 69: 95–100.
  11. Cooper N., Stasi R., Cunningham-Rundles S. et al. The efficacy and safety of B-cell depletion with anti-CD20 monoclonal antibody in adults with chronic immune thrombocytopenic purpura. Br. J. Haematol. 2004; 125: 232–9.
  12. Ahmad H.N., Ball C., Height S.E., Rees D.C. Rituximab in chronic, recurrent HIV-associated immune thrombocytopenic purpura. Br. J. Haematol. 2004; 127: 607–8.
  13. Stasi R., Pagano A., Stipa E., Amadori S. Rituximab chimeric anti-CD20 monoclonal antibody treatment for adults with chronic idiopathic thrombocytopenic purpura. Blood 2001; 98: 952–7.
  14. Волкова М.А., Бялик Т.Е. Ритуксимаб в терапии аутоиммунных осложнений при хроническом лимфолейкозе. Гематол. и трансфузиол. 2006; 3: 11–7. [Volkova M.A., Byalik T.E. Rituksimab v terapii autoimmunnykh oslozhnenii pri khronicheskom limfoleikoze (Rituximab treatment of autoimmune complications in chronic lymphocytic leukemia). Gematol. i transfuziol. 2006; 3: 11–7.]
  15. Филатов Л.Б., Томилов А.Ф., Алексеева Т.А. Гемолитическая анемия, вызванная фрагментацией эритроцитов. Клин. онкогематол. 2011; 4(4): 346–55. [Filatov L.B., Tomilov A.F., Alekseeva T.A. Gemoliticheskaya anemiya, vyzvannaya fragmentatsiei eritrotsitov (Hemolytic anemia induced by erythrocyte fragmentation). Klin. onkogematol. 2011; 4(4): 346–55.]
  16. Ross C.L., Hunt B.J., Wyncoll D. et al. HIV, thrombotic thrombocytopaenic purpura and rituximab in a violent noncompliant patient. Blood Coagul. Fibrinol. 2009; 20: 157–60.
  17. Evans M.W., Vaughan L.B., Giffi V.S. et al. Rituximab Treatment for Thrombotic Thrombocytopenic Purpura Associated with Human Immunodeficiency Virus Failing Extensive Treatment with Plasma Exchange: A Report of Two Cases. AIDS Patient Care STDs 2010; 24(6): 349–52.
  18. Goedert J.J., Cote T.R., Virgo P. et al. Spectrum of AIDS-associated malignant disorders. Lancet 1998; 351: 1833–
  19. Clarke C.A., Glaser S.L. Epidemiological trends in HIV-associated lymphomas. Curr. Opin. Oncol. 2001; 13: 354–9.
  20. Little R.F. AIDS-related non-Hodgkin’s lymphoma: etiology, epidemiology, and impact of highly active antiretroviral therapy. Lymphoma 2003; 44(3): 63–8.
  21. Gerard L., Galicier L., Maillard A. et al. Systemic non-Hodgkin lymphoma in HIV-infected patients with effective suppression of HIV replication: persistent occurrence but improved survival. AIDS 2002; 30: 478–84.
  22. Glaser S.L., Clarke C.A., Gulley M.L. et al. Population-based patterns of human immunodeficiency virus-related Hodgkin lymphoma in the Great San Francisco Bay Area, 1988–1998. Cancer 2003; 98(2): 300–9.
  23. Powles T., Imami N., Nelson M. et al. Effects of combination chemotherapy and HAART on immune parameters in HIV-1 associated lymphoma. AIDS 2002; 16: 531–620.
  24. Пивник А.В., Пархоменко Ю.Г., Криволапов Ю.А. и др. Соматические проблемы ВИЧ-медицины: СПИД-ассоциированные лимфомы. Онкогематология 2007; 3: 27–37. [Pivnik A.V., Parkhomenko Yu.G., Krivolapov Yu.A. i dr. Somaticheskie problemy VICh-meditsiny: SPID-assotsiirovannye limfomy (Somatic problems of HIV medicine: AIDS-associated lymphomas). Onkogematologiya 2007; 3: 27–37.]
  25. Ribera J.M., Oriol A., Morgades M. et al. Safety and efficacy of cyclophosphamide, adriamycin, vincristine, prednisone and rituximab in patients with human immunodeficiency virus-associated diffuse large B-cell lymphoma: results of a phase II trial. Br. J. Haematol. 2008; 140(4): 411–9.
  26. Sparano J.A., Lee J.Y., Kaplan L.D. et al. Rituximab plus concurrent infusional EPOCH chemotherapy is highly effective in HIV-associated B-cell non-Hodgkin lymphoma. Blood 2010; 115(15): 3008–16.
  27. Dunleavy K., Little R.F., Pittaluga S. et al. The role of tumor histogenesis, FDG-PET, and short-course EPOCH with dose-dense rituximab (SC-EPOCH-RR) in HIV-associated diffuse large B-cell lymphoma. Blood 2010; 115(15): 3017–24.
  28. Gang A.O., Strom C., Pedersen M. et al. R-CHOEP-14 improves overall survival in young high-risk patients with diffuse large B-cell lymphoma compared with R-CHOP-29. A population-based investigation from the Danish Lymphoma Group. Ann. Oncol. 2012; 23: 147–53.
  29. Mazloom A., Fowler N., Medeiros L.J. et al. Outcome of patients with diffuse large B-cell lymphoma of the testis by era of treatment: the M. D. Anderson Cancer Center experience. Lymphoma 2010; 51(7): 1217–24.
  30. Simonelli C., Zanussi S., Cinelli R. et al. Impact of concomitant antiblastic chemotherapy and highly active antiretroviral therapy on human immunodeficiency virus (HIV) viremia and genotyping in HIV-infected patients with non-Hodgkin lymphoma. Infect. Dis. 2003; 37: 820–7.
  31. Powles T., Imami N., Nelson M. et al. Effects of combination chemotherapy and highly active antiretroviral therapy on immune parameters in HIV-1 associated lymphoma. AIDS 2002; 16: 531–6.
  32. Пивник А.В., Серегин Н.В., Туманова М.В. и др. Агрессивные лимфомы полости рта и придаточных пазух носа у больных СПИДом. Описание 9случаев. Клин. онкогематол. 2009; 2(4): 349–57. [Pivnik A.V., Seregin N.V., Tumanova M.V. i dr. Agressivnye limfomy polosti rta i pridatochnykh pazukh nosa u bol’nykh SPIDom. Opisanie 9 sluchaev (Aggressive lymphomas of oral cavity and accessory nasal sinuses in AIDS patients: 9 cases report). Klin. onkogematol. 2009; 2(4): 349–57.]
  33. van Aalderen M.C., Brinkman K., van den Berk G.E., Terpstra W.E. Vinblastine, rituximab and HAART, treatment of an HIV-positive patient with multicentric Castleman’s disease. J. Med. 2010; 68(2): 87–90.
  34. Hoffmann C., Schmid H., Muller M. et al. Improved outcome with rituximab in patients with HIV-associated multicentric Castleman disease. Blood 2011; 118: 3499–503.
  35. Johns R.H., Doyle T., Lipman M.C. et al. Successful treatment of HIV-associated multicentric Castleman’s disease and multiple organ failure with rituximab and supportive care: a case report. J. Med. Case Rep. 2010; 4: 32.
  36. Bower M., Powles T., Williams S. et al. Brief communication: rituximab in HIV-associated multicentric Castleman disease. Intern. Med. 2007; 147(12): 836–9.
  37. Gerard L., Berezne A., Galicier L. et al. Prospective study of rituximab in chemotherapy dependent human immunodeficiency virus associated multicentric Castleman’s disease: ANRS 117 CastlemaB Trial. J. Clin. Oncol. 2007; 25(22): 3350–6.
  38. Bower M., Veraitch O., Szydlo R. et al. Cytokine changes during rituximab therapy in HIV-associated multicentric Castleman disease. Blood 2009; 113(19): 4521–4.
  39. Marcelin A.-G., Aaron L., Mateus C. et al. Rituximab therapy for HIV-associated Castleman disease: long-term remission of Kaposi sarcoma-associated herpesvirus-related multicentric Castleman disease with anti-CD20 monoclonal antibody therapy. Blood 2003; 102(8): 2786–8.
  40. Neuville S., Agbalika F., Rabian C. et al. Failure of rituximab in human immunodeficiency virus-associated multicentric Castleman disease. J. Hematol. 2005; 79(4): 337–9.
  41. Buchler T., Dubash S., Lee V. et al. Rituximab failure in fulminant multicentric HIV/human herpesvirus 8-associated Castleman’s disease with multiorgan failure: report of two cases. AIDS 2008; 22(13): 1685–7.
  42. Rodriguez J., Gutierrez A., Palacios A. et al. Rituximab, gemcitabine and oxaliplatin: an effective regimen in patients with refractory and relapsing mantle cell lymphoma. Leuk. Lymphoma 2007; 48(11): 2172–8.
  43. Spurgeon S.E., Pindyck T., Okada C. et al. Cladribine plus rituximab is an effective therapy for newly diagnosed mantle cell lymphoma. Leuk. Lymphoma 2011; 52(8): 1488–94.
  44. Sachanas S., Pangalis G.A., Vassilakopoulos T.P. et al. Combination of rituximab with chlorambucil as first line treatment in patients with mantle cell lymphoma: a highly effective regimen. Leuk. Lymphoma 2011; 52(3): 387–93.
  45. Barnes J.A., LaCasce A.S., Feng Y. et al. Evaluation of the addition of rituximab to CODOX-M/IVAC for Burkitt’s lymphoma: a retrospective analysis. Ann. Oncol. 2011; 22: 1859–64.
  46. Crosswell H.E., Bergsagel D.J., Yost R., Lew G. Successful treatment with modified CHOP-rituximab in pediatric AIDS-related advanced stage Burkitt lymphoma. Pediatr. Blood Cancer 2008; 50(4): 883–5.
  47. Rodrigo J.A., Hicks L.K., Cheung M.C. et al. HIV-Associated Burkitt Lymphoma: Good Efficacy and Tolerance of Intensive Chemotherapy Including CODOX-M/IVAC with or without Rituximab in the HAART Era. Advances in Hematology, 2012, Article ID 735392.
  48. Dunleavy K., Wilson W.H. How I treat HIV-associated lymphoma. Blood 2012; 119: 3245–55.
  49. Pei S.N., Chen C.H., Lee C.M. et al. Reactivation of hepatitis B virus following rituximab-based regimens: a serious complication in both HBsAg-positive and HBsAg-negative patients. Hematol. 2010; 89: 255–62.
  50. Matsue K., Kimura S., Takanashi Y. et al. Reactivation of hepatitis B virus after rituximab-containing treatment in patients with CD20-positive B-cell lymphoma. Cancer 2010; 116(20): 4769–76.
  51. Boyle S.F., Reid E.G. Viral reactivation and clinical hepatitis in patients with hepatitis C who receive rituximab as part of chemotherapy for treatment of lymphoma: A case series. ASCO Meeting Abstracts 2010; 28: e18559.
  52. Carson K.R., Focosi D., Major E.O. et al. Monoclonal antibody-associated progressive multifocal leucoencephalopathy in patients treated with rituximab, natalizumab, and efalizumab: a Review from the Research on Adverse Drug Events and Reports (RADAR) Project. Lancet Oncol. 2009; 10(8): 816–24.
  53. Carson K.R., Evens A.M., Richey E.A. et al. Progressive multifocal leukoencephalopathy after rituximab therapy in HIV-negative patients: a report of 57 cases from the Research on Adverse Drug Events and Reports project. Blood 2009 14; 113(20): 4834–40.