%0 Journal Article
%T Improvements in Immune Function and Activation with 48-Week Darunavir/Ritonavir-Based Therapy: GRACE Substudy
%A Christos Tsoukas
%A Louise Gilbert
%A Trevor Lewis
%A George Hatzakis
%A Ron Falcon
%A Joseph Mrus
%J ISRN AIDS
%D 2013
%R 10.1155/2013/358294
%X Objective. During the course of HIV infection, progressive immune deficiency occurs. The aim of this prospective substudy was to evaluate the recovery of functional immunity in a subset of patients from the GRACE (Gender, Race, And Clinical Experience) study treated with a DRV/r-based regimen. Methods. The recovery of functional immunity with a darunavir/ritonavir-based regimen was assessed in a subset of treatment-experienced, HIV-1 infected patients from the GRACE study. Results. 19/32 patients (59%) enrolled in the substudy were virologically suppressed (<50 copies/mL). In these patients, median (range) CD4+ cell count increased from 222 (2, 398) cells/mm3 at baseline to 398 (119, 812) cells/mm3 at Week 48. CD8+% decreased significantly from baseline to Week 48 ( ). Proliferation of CD4+ lymphocytes in response to CD3+/CD28+, phytohemagglutinin, and pokeweed was significantly increased ( ) by Week 12. Proliferation in response to Candida and tetanus was significantly increased by Week 48 ( and , resp.). Staphylococcal enterotoxin B-stimulated tumor necrosis factor-alpha and interleukin-2 in CD4+ cells was significantly increased by Week 12 ( ) and Week 48 ( ), respectively. Conclusions. Darunavir/ritonavir-based therapy demonstrated improvements in CD4+ cell recovery and association with progressive functional immune recovery over 48 weeks. This trial is registered with NCT00381303. 1. Introduction During the course of HIV-1 infection, multifactorial T-lymphocyte (T-cell)-mediated mechanisms contribute to the progressive loss of host immune function [1¨C5]. In infected individuals, immune dysregulation occurs early and is characterized by a decrease in CD4+ cell count, a concurrent rise in CD8+ cells, a progressive decline in the CD4+/CD8+ ratio, and defective thymocyte proliferation [6]. During late-stage disease, loss of T-cell homeostasis also occurs [7, 8]. T cells are chronically activated throughout the course of HIV infection, as indicated by an increase in the expression of the antigens Ki67, CD38, and human leukocyte antigen (HLA)-DR, with CD38 recognized as the most reliable marker of immune activation [1¨C3, 5, 9]. Immune activation provides the virus with a steady pool of target cells and has been linked with increased polyclonal T-cell proliferation and turnover, as well as increases in the apoptotic marker CD95 [10¨C13] and activation-induced cell death [12, 14¨C16]. Concomitant with the decline of CD4 cells in the peripheral blood, the frequency of the CD4+ CD28 null subset increases with disease progression and eventual progression to
%U http://www.hindawi.com/journals/isrn.aids/2013/358294/