Abstract
BackgroundThe 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. MethodsThirty-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. ResultsInitiation 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. ConclusionsART 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 RegistrationClinicaltrials.gov NCT00660972
Highlights
HIV-1 infection is characterized by T cell activation, inflammation, and hyper-coagulation, yet, effects of antiretroviral therapy (ART) on dynamics of these indices and correlates of CD4+ T cell reconstitution are incompletely understood
As ART results in decreased plasma levels of HIV-1 and both plasma inflammatory markers and cellular markers of T cell activation [9,10,16,17,18], we hypothesized that a detailed assessment of the decay dynamics of these indices after ART initiation would provide insight into the determinants of immune restoration in treated HIV-1 infection; and, by inference, into the determinants of cellular turnover, inflammation, and immune deficiency in HIV-1 disease
In subjects who exhibited virologic failure (VF) or clinical rebound (CR) at any time on or before week 48, data are excluded after the earliest such event
Summary
HIV-1 infection is characterized by T cell activation, inflammation, and hyper-coagulation, yet, effects of antiretroviral therapy (ART) on dynamics of these indices and correlates of CD4+ T cell reconstitution are incompletely understood. 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. 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 HIVseronegatives through 48 weeks of viral control.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
