%0 Journal Article
%T HIV Patients Developing Primary CNS Lymphoma Lack EBV-Specific CD4+ T Cell Function Irrespective of Absolute CD4+ T Cell Counts
%A Olivier Gasser
%A Florian K Bihl
%A Marcel Wolbers
%A Elisabetta Loggi
%A Ingrid Steffen
%A Hans H Hirsch
%A Huldrych F G¨¹nthard
%A Bruce D Walker
%A Christian Brander
%A Manuel Battegay
%A Christoph Hess
%A for the Swiss HIV Cohort Study
%J PLOS Medicine
%D 2007
%I Public Library of Science (PLoS)
%R 10.1371/journal.pmed.0040096
%X Background In chronic HIV infection, antiretroviral therapy¨Cinduced normalization of CD4+ T cell counts (immune reconstitution [IR]) is associated with a decreased incidence of opportunistic diseases. However, some individuals remain at risk for opportunistic diseases despite prolonged normalization of CD4+ T cell counts. Deficient Epstein-Barr virus (EBV)-specific CD4+ T cell function may explain the occurrence of EBV-associated opportunistic malignancy¡ªsuch as primary central nervous system (PCNS) lymphoma¡ªdespite recovery of absolute CD4+ T cell counts. Methods and Findings Absolute CD4+ T cell counts and EBV-specific CD4+ T cell-dependent interferon-¦Ã production were assessed in six HIV-positive individuals prior to development of PCNS lymphoma (¡°cases¡±), and these values were compared with those in 16 HIV-infected matched participants with no sign of EBV-associated pathology (¡°matched controls¡±) and 11 nonmatched HIV-negative blood donors. Half of the PCNS lymphoma patients fulfilled IR criteria (defined here as CD4+ T cell counts ¡Ý500/¦Ìl blood). EBV-specific CD4+ T cells were assessed 0.5¨C4.7 y prior to diagnosis of lymphoma. In 0/6 cases versus 13/16 matched controls an EBV-specific CD4+ T cell response was detected (p = 0.007; confidence interval for odds ratio [0¨C0.40]). PCNS lymphoma patients also differed with regards to this response significantly from HIV-negative blood donors (p < 0.001, confidence interval for odds ratio [0¨C0.14]), but there was no evidence for a difference between HIV-negative participants and the HIV-positive matched controls (p = 0.47). Conclusions Irrespective of absolute CD4+ T cell counts, HIV-positive patients who subsequently developed PCNS lymphoma lacked EBV-specific CD4+ T cell function. Larger, ideally prospective studies are needed to confirm these preliminary data, and clarify the impact of pathogen-specific versus surrogate marker-based assessment of IR on clinical outcome.
%U http://www.plosmedicine.org/article/info%3Adoi%2F10.1371%2Fjournal.pmed.0040096