title: Transcriptional Changes in CD8(+) T Cells During Antiretroviral Therapy Intensified With Raltegravir.
abstract: Background.  Intensification of antiretroviral therapy with raltegravir does not affect levels of residual human immunodeficiency virus (HIV)-1 viremia, but it has led to increased levels of episomal HIV-1 DNA in some patients, suggesting antiviral activity against otherwise unresponsive components of the viral reservoir. Effects of raltegravir on host cells remain less well understood. Methods.  We used comprehensive and unbiased microarray-based transcriptional profiling to analyze gene expression changes in CD8(+) T cells from participants in a randomized clinical trial (AIDS Clinical Trials Group [ACTG] A5244) comparing raltegravir-intensified to nonintensified antiretroviral therapy. Results.  Although raltegravir intensification failed to induce statistically significant changes in HIV-1 DNA or residual plasma viremia, we observed significant increases in the expression intensity of 121 host gene transcripts. In functional annotations of these transcripts, we found that they were mainly involved in glucose and carbohydrate metabolism, immune regulation, control of cell proliferation, and tumor suppression. Two of the raltegravir-responsive gene transcripts were statistically correlated with levels of residual HIV-1 RNA, but none of the remaining 119 transcripts were associated with immunologic or virologic characteristics of the study patients. Conclusions.  Together, these findings demonstrate that raltegravir intensification can induce previously unrecognized, statistically significant gene expression changes in host CD8(+) T lymphocytes.
authors.affiliation: Ragon Institute of MGH, MIT and Harvard , Cambridge, Massachusetts.
authors.forename: Zhengyu
authors.initials: Z
authors.lastname: Ouyang
authors.affiliation: Ragon Institute of MGH, MIT and Harvard , Cambridge, Massachusetts ; Division of Infectious Diseases , Massachusetts General Hospital , Boston.
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Buzon
authors.affiliation: Center for Biostatistics in AIDS Research , Harvard School of Public Health , Boston, Massachusetts.
authors.forename: Lu
authors.initials: L
authors.lastname: Zheng
authors.affiliation: Ragon Institute of MGH, MIT and Harvard , Cambridge, Massachusetts.
authors.forename: Hong
authors.initials: H
authors.lastname: Sun
authors.affiliation: Ragon Institute of MGH, MIT and Harvard , Cambridge, Massachusetts.
authors.forename: Xu G
authors.initials: XG
authors.lastname: Yu
authors.affiliation: Center for Biostatistics in AIDS Research , Harvard School of Public Health , Boston, Massachusetts.
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Bosch
authors.affiliation: Division of Infectious Diseases , University of Pittsburgh , Pennsylvania.
authors.forename: John W
authors.initials: JW
authors.lastname: Mellors
authors.affiliation: Division of Infectious Diseases , University of North Carolina , Chapel Hill.
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Eron
authors.affiliation: Ragon Institute of MGH, MIT and Harvard , Cambridge, Massachusetts ; Division of Infectious Diseases , Massachusetts General Hospital , Boston.
authors.forename: Rajesh T
authors.initials: RT
authors.lastname: Gandhi
authors.affiliation: Division of Infectious Diseases , Massachusetts General Hospital , Boston.
authors.forename: Mathias
authors.initials: M
authors.lastname: Lichterfeld
keywords: CD8 T cells; HIV-1; antiretroviral therapy; gene expression profiling; raltegravir