[HTML][HTML] Dynamics of immune reconstitution and activation markers in HIV+ treatment-naive patients treated with raltegravir, tenofovir disoproxil fumarate and …

NT Funderburg, A Andrade, ES Chan, SL Rosenkranz… - PloS one, 2013 - journals.plos.org
NT Funderburg, A Andrade, ES Chan, SL Rosenkranz, D Lu, B Clagett, HA Pilch-Cooper…
PloS one, 2013journals.plos.org
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 …
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
PLOS