Funderburg, Nicholas T.Andrade, AdrianaChan, EllenRosenkranz, SusanLu, DarleneClagett, BrianPilch-Cooper, Heather A.Rodriguez, BenignoFeinberg, JudithDaar, EricMellors, JohnKuritzkes, DanielJacobson, Jeffrey M.Lederman, Michael M.2014-03-112013Funderburg, N. T., A. Andrade, E. S. Chan, S. L. Rosenkranz, D. Lu, B. Clagett, H. A. Pilch-Cooper, et al. 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. doi:10.1371/journal.pone.0083514. http://dx.doi.org/10.1371/journal.pone.0083514.1932-6203http://nrs.harvard.edu/urn-3:HUL.InstRepos:11879234Background: 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 NCT00660972en-USJournal Article2014-03-1110.1371/journal.pone.0083514