Leukocyte-Reduced Red Blood Cell Transfusions in Patients With Anemia and Human Immunodeficiency Virus Infection: The Viral Activation Transfusion Study: A Randomized Controlled Trial

• Published in: JAMA : the journal of the American Medical Association 2001-03, Vol.285 (12), p.1592-1601
• Main Authors: Collier, Ann C, Kalish, Leslie A, Busch, Michael P, Gernsheimer, Terry, Assmann, Susan F, Lane, Thomas A, Asmuth, David M, Lederman, Michael M, Murphy, Edward L, Kumar, Princy, Kelley, Meera, Flanigan, Timothy P, McMahon, Deborah K, Sacks, Henry S, Kennedy, Melanie S, Holland, Paul V, for the Viral Activation Transfusion Study Group
• Format: Article
• Language: English
• Subjects: Adult; AIDS-Related Opportunistic Infections - complications; AIDS-Related Opportunistic Infections - immunology; Anemia - complications; Anemia - immunology; Anemia - therapy; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Biological and medical sciences; Blood. Blood and plasma substitutes. Blood products. Blood cells. Blood typing. Plasmapheresis. Apheresis; CD4 Lymphocyte Count; Cytokines - blood; Cytomegalovirus - genetics; Cytomegalovirus Infections - complications; Cytomegalovirus Infections - immunology; DNA, Viral - analysis; Double-Blind Method; Erythrocyte Transfusion - methods; Female; HIV Infections - complications; HIV Infections - immunology; HIV Infections - physiopathology; Human viral diseases; Humans; Infectious diseases; Leukocytes; Lymphocyte Subsets; Male; Medical sciences; Prospective Studies; Survival Analysis; Transfusions. Complications. Transfusion reactions. Cell and gene therapy; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Viral Load; Virus Activation
• ISSN: 0098-7484; 1538-3598
• DOI: 10.1001/jama.285.12.1592

CONTEXT Allogeneic blood transfusions have immunomodulatory effects and have been associated with activation of human immunodeficiency virus (HIV) and cytomegalovirus (CMV) in vitro and of HIV in small pilot studies. Retrospective studies suggest that transfusions adversely affect the clinical course of HIV. Data in selected non–HIV-infected patients requiring blood transfusion have suggested clinical benefit with leukocyte-reduced red blood cells (RBCs). OBJECTIVE To compare the effects of leukoreduced and unmodified RBC transfusions on survival, complications of acquired immunodeficiency syndrome, and relevant laboratory markers in HIV-infected patients. DESIGN AND SETTING Double-blind randomized controlled trial conducted in 11 US academic medical centers from July 1995 through June 1999, with a median follow-up of 12 months (24 months in survivors). PATIENTS A total of 531 persons infected with HIV and CMV, aged 14 years or older, who required transfusions for anemia; 259 received leukoreduced transfusions and 262 received unmodified transfusions (10 did not receive the planned transfusion). MAIN OUTCOME MEASURES Survival and change in plasma HIV RNA level 7 days after transfusion, compared by type of transfusion. RESULTS At entry, the groups were similar in demographic, clinical, and relevant laboratory characteristics. A total of 3864 RBC units were transfused. Two hundred eighty-nine deaths occurred (151 with leukoreduced transfusion; 138 with unmodified transfusion); median survival was 13.0 and 20.5 months, respectively (relative hazard [RH], 1.20; 95% confidence interval [CI], 0.95-1.51; log-rank P = .12). Analyses adjusted for prognostic factors suggested possible worse survival with leukoreduction (RH, 1.35; 95% CI, 1.06-1.72). There was no difference in time to new opportunistic event/death or frequency of transfusion reactions. No changes in plasma HIV RNA level were seen in either group at days 7, 14, 21, or 28, even in patients not taking antiretroviral drugs. There were no differences in trends between groups in CMV DNA, CD4 cell counts, activated (CD38% or human leukocyte antigen-DR) CD8 cell counts, or plasma cytokine levels. CONCLUSIONS We found no evidence of HIV, CMV, or cytokine activation following blood transfusion in patients with advanced HIV infection. Leukoreduction provided no clinical benefit in these patients. These data demonstrate the importance of conducting controlled studies of effects of leukoreduction in different pat