Dynamics of immune reconstitution and activation markers in HIV+ treatment-naïve patients treated with raltegravir, tenofovir disoproxil fumarate and emtricitabine

Nicholas T. Funderburg, Adriana Andrade, Ellen S. Chan, Susan L. Rosenkranz, Darlene Lu, Brian Clagett, Heather A. Pilch-Cooper, Benigno Rodriguez, Judith Feinberg, Eric Daar, John Mellors, Daniel Kuritzkes, Jeffrey M. Jacobson, Michael M. Lederman

Research output: Contribution to journalArticle

Abstract

Background: The dynamics of CD4+ T cell reconstitution and changes in immune activation and inflammation in HIV-1 disease following initiation of antiretroviral therapy (ART) are incompletely defined and their underlying mechanisms poorly understood. Methods: Thirty-nine treatment-naïve patients were treated with raltegravir, tenofovir DF and emtricitabine. Immunologic and inflammatory indices were examined in persons with sustained virologic control during 48 weeks of therapy. Results: Initiation of ART increased CD4+ T cell numbers and decreased activation and cell cycle entry among CD4+ and CD8+ T cell subsets, and attenuated markers of coagulation (D-dimer levels) and inflammation (IL-6 and TNFr1). These indices decayed at different rates and almost all remained elevated above levels measured in HIV-seronegatives through 48 weeks of viral control. Greater first and second phase CD4+ T cell restoration was related to lower T cell activation and cell cycling at baseline, to their decay with treatment, and to baseline levels of selected inflammatory indices, but less so to their changes on therapy. Conclusions: ART initiation results in dynamic changes in viral replication, T cell restoration, and indices of immune activation, inflammation, and coagulation. These findings suggest that determinants of T cell activation/cycling and inflammation/coagulation may have distinguishable impact on immune homeostasis. Trial Registration: Clinicaltrials.gov NCT00660972

Original languageEnglish (US)
Article numbere83514
JournalPloS one
Volume8
Issue number12
DOIs
StatePublished - Dec 18 2013

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Funderburg, N. T., Andrade, A., Chan, E. S., Rosenkranz, S. L., Lu, D., Clagett, B., Pilch-Cooper, H. A., Rodriguez, B., Feinberg, J., Daar, E., Mellors, J., Kuritzkes, D., Jacobson, J. M., & Lederman, M. M. (2013). Dynamics of immune reconstitution and activation markers in HIV+ treatment-naïve patients treated with raltegravir, tenofovir disoproxil fumarate and emtricitabine. PloS one, 8(12), [e83514]. https://doi.org/10.1371/journal.pone.0083514