TY - JOUR
T1 - Dynamics of immune reconstitution and activation markers in HIV+ treatment-naïve patients treated with raltegravir, tenofovir disoproxil fumarate and emtricitabine
AU - Funderburg, Nicholas T.
AU - Andrade, Adriana
AU - Chan, Ellen S.
AU - Rosenkranz, Susan L.
AU - Lu, Darlene
AU - Clagett, Brian
AU - Pilch-Cooper, Heather A.
AU - Rodriguez, Benigno
AU - Feinberg, Judith
AU - Daar, Eric
AU - Mellors, John
AU - Kuritzkes, Daniel
AU - Jacobson, Jeffrey M.
AU - Lederman, Michael M.
N1 - Funding Information:
M.M.L. has served as consultant for Merck. D.R.K. has served as a consultant for Merck and Gilead and has received grant support from both companies; in addition, he has received an honorarium for speaking at Gilead. J.W.M is a consultant for Gilead and holds share options in RFS Pharmaceuticals. E.S.D. has received research grant support from Abbott, Gilead, Merck and ViiV as well as served as a consultant for Bristol Myers Squibb, Gilead, Janssen, Merck and ViiV. The authors' competeting interests do not alter our adherence to all the PLOS ONE policies on sharing data and materials.
PY - 2013/12/18
Y1 - 2013/12/18
N2 - 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
AB - 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
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U2 - 10.1371/journal.pone.0083514
DO - 10.1371/journal.pone.0083514
M3 - Article
C2 - 24367599
AN - SCOPUS:84893171544
SN - 1932-6203
VL - 8
JO - PloS one
JF - PloS one
IS - 12
M1 - e83514
ER -