Clinical implications of discordant viral and immune outcomes following protease inhibitor containing antiretroviral the
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Clinical implications of discordant viral and immune outcomes following protease inhibitor containing antiretroviral therapy for HIV-infected children Carina A. Rodriguez Æ Sarah Koch Æ Maureen Goodenow Æ John W. Sleasman
Published online: 19 October 2007 Humana Press Inc. 2007
Abstract Many HIV-infected children treated with protease inhibitors (PI) reconstitute immunity despite viral breakthrough predicting disease progression. We studied a unique cohort of PI treated children with advanced disease who demonstrated sustained CD4 T cell counts but median post therapy viral load rebounded to [4.0 log10 copies/ml. Phylogenetic relationships between pre- and post-therapy viruses reveals significant bottlenecks for quasispecies with natural polymorphisms mapping outside of protease active site providing selective advantage for emergence. Among discordant subjects post-therapy viruses fell into two phenotypes; high viral loads (median [5.0 log10 copies/ml) and Dedication to Dr. Robert A. Good: In many ways the HIV epidemic has defined modern human immunology. Early in the epidemic there was no readily available animal model to study pathogenesis. As a result physicians had to rely on clinical observations to understand disease progression and the factors leading to the development of AIDS. Imagine if Dr. Good’s early work in defining the compartmentalization of adaptive immunity into T and B lymphocytes or his discovery of the important role of the thymus in T cell development had NOT occurred or happened years later? There would have been confusion and frustration in understanding, treating, and controlling this great new plague of mankind. Fortunately Dr. Good’s focus on human immunology as well as his keen ability to make clinical observations and correlate them with functional immunity provided the basis of the future studies that defined the human immune system. Dr. Good and his collaborator’s research facilitated the discovery of CD4 and CD8 T cells and laid the foundation for our understanding T cell homeostasis. Was it pure serendipity that the timeline of the most important human immune deficiency paralleled the great discoveries of human immunology spearheaded by Dr. Robert Good? C. A. Rodriguez J. W. Sleasman (&) Department of Pediatrics, Division of Allergy, Immunology and Rheumatology, University of South Florida, College of Medicine, All Children’s Hospital, 801 6th St. South, Dept 9350, St. Petersburg, FL 33701-4899, USA e-mail: [email protected] C. A. Rodriguez Division of Infectious Diseases, University of South Florida, College of Medicine, All Children’s Hospital, St. Petersburg, FL, USA S. Koch M. Goodenow Department of Pathology, Immunology, and Laboratory Medicine, University of Florida, College of Medicine, Gainesville, FL, USA
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Immunol Res (2008) 40:271–286
attenuated post-therapy replication (median \4.0 log10 copies/ml). Both groups showed similar degrees of CD4 T cell immune reconstitution and were similar to children who optimally suppressed virus to\400 copies/ml. Both high
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