Leukocyte-reduced red blood cell transfusions in patients with anemia and human immunodeficiency virus infection - The viral activation transfusion study: A randomized controlled trial

Context Allogeneic blood transfusions have immunomodulatory effects and hav e been associated with activation of human immunodeficiency virus (HIV) and cytomegalovirus (CMV) in vitro and of HIV in small pilot studies. Retrospe ctive studies suggest that transfusions adversely affect the clinical cours e of HIV. Data in selected non-HIV-infected patients requiring blood transf usion have suggested clinical benefit with leukocyte-reduced red blood cell s (RBCs). Objective To compare the effects of leukoreduced and unmodified RBC transfu sions 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 media n 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 tra nsfusions 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 af ter transfusion, compared by type of transfusion. Results At entry, the groups were similar in demographic, clinical, and rel evant laboratory characteristics. A total of 3864 RBC units were transfused . Two hundred eighty-nine deaths occurred (151 with leukoreduced transfusio n; 138 with unmodified transfusion); median survival was 13.0 and 20.5 mont hs, respectively (relative hazard [RH], 1.20; 95% confidence interval [CI], 0.95-1.51; log-rank P = .12). Analyses adjusted for prognostic factors sug gested 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 i n 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 follow ing blood transfusion in patients with advanced HIV infection, Leukoreducti on provided no clinical benefit in these patients. These data demonstrate t he importance of conducting controlled studies of effects of leukoreduction in different patient populations, since smaller studies in other patient p opulations have suggested leukoreduction may be beneficial.