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PLoS One. 2013 Dec 18;8(12):e83514. doi: 10.1371/journal.pone.0083514. eCollection 2013.

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

Author information

1
Case Western Reserve University, Division of Infectious Diseases and HIV Medicine, Cleveland, Ohio, United States of America.
2
The Johns Hopkins University, Baltimore, Maryland, United States of America.
3
Center for Biostatistics in AIDS Research, Harvard School of Public Health, Boston, Massachusetts, United States of America.
4
University of Cincinnati Medical Center, Cincinnati, Ohio, United States of America.
5
Los Angeles Biomedical Research Institute at Harbor UCLA Medical Center, Torrance, California, United States of America.
6
University of Pittsburg Medical Center, Pittsburg, Pennsylvania, United States of America.
7
Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, United States of America.
8
Drexel University College of Medicine, Philadelphia, Pennsylvania, United States of America.

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.

PMID:
24367599
PMCID:
PMC3867440
DOI:
10.1371/journal.pone.0083514
[Indexed for MEDLINE]
Free PMC Article

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