TY - JOUR
T1 - Intensification of antiretroviral therapy with a CCR5 antagonist in patients with chronic HIV-1 infection
T2 - Effect on T cells latently infected
AU - Gutiérrez, Carolina
AU - Díaz, Laura
AU - Vallejo, Alejandro
AU - Hernández-Novoa, Beatriz
AU - Abad, María
AU - Madrid, Nadia
AU - Dahl, Viktor
AU - Rubio, Rafael
AU - Moreno, Ana M.
AU - Dronda, Fernando
AU - Casado, José Luis
AU - Navas, Enrique
AU - Pérez-Elías, María Jesús
AU - Zamora, Javier
AU - Palmer, Sarah
AU - Muñoz, Eduardo
AU - Muñoz-Fernández, María Ángeles
AU - Moreno, Santiago
PY - 2011/12/8
Y1 - 2011/12/8
N2 - Objective: The primary objective was to assess the effect of MVC intensification on latently infected CD4 + T cells in chronically HIV-1-infected patients receiving antiretroviral therapy. Methods: We performed an open-label pilot phase II clinical trial involving chronically HIV-1-infected patients receiving stable antiretroviral therapy whose regimen was intensified with 48 weeks of maraviroc therapy. We analyzed the latent reservoir, the residual viremia and episomal 2LTR DNA to examine the relationship between these measures and the HIV-1 latent reservoir, immune activation, lymphocyte subsets (including effector and central memory T cells), and markers associated with bacterial translocation. Results: Overall a non significant reduction in the size of the latent reservoir was found (p = 0.068). A mean reduction of 1.82 IUPM was observed in 4 patients with detectable latent reservoir at baseline after 48 weeks of intensification. No effect on plasma residual viremia was observed. Unexpectedly, all the patients had detectable 2LTR DNA circles at week 24, while none of them showed those circles at the end of the study. No changes were detected in CD4 + or CD8 + counts, although a significant decrease was found in the proportion of HLA-DR +/CD38 + CD4 + and CD8 + T-cells. LPS and sCD14 levels increased. Conclusions: Intensification with MVC was associated with a trend to a decrease in the size of the latent HIV-1 reservoir in memory T cells. No impact on residual viremia was detected. Additional studies with larger samples are needed to confirm the results. Trial Registration: ClinicalTrials.gov NCT00795444.
AB - Objective: The primary objective was to assess the effect of MVC intensification on latently infected CD4 + T cells in chronically HIV-1-infected patients receiving antiretroviral therapy. Methods: We performed an open-label pilot phase II clinical trial involving chronically HIV-1-infected patients receiving stable antiretroviral therapy whose regimen was intensified with 48 weeks of maraviroc therapy. We analyzed the latent reservoir, the residual viremia and episomal 2LTR DNA to examine the relationship between these measures and the HIV-1 latent reservoir, immune activation, lymphocyte subsets (including effector and central memory T cells), and markers associated with bacterial translocation. Results: Overall a non significant reduction in the size of the latent reservoir was found (p = 0.068). A mean reduction of 1.82 IUPM was observed in 4 patients with detectable latent reservoir at baseline after 48 weeks of intensification. No effect on plasma residual viremia was observed. Unexpectedly, all the patients had detectable 2LTR DNA circles at week 24, while none of them showed those circles at the end of the study. No changes were detected in CD4 + or CD8 + counts, although a significant decrease was found in the proportion of HLA-DR +/CD38 + CD4 + and CD8 + T-cells. LPS and sCD14 levels increased. Conclusions: Intensification with MVC was associated with a trend to a decrease in the size of the latent HIV-1 reservoir in memory T cells. No impact on residual viremia was detected. Additional studies with larger samples are needed to confirm the results. Trial Registration: ClinicalTrials.gov NCT00795444.
UR - http://www.scopus.com/inward/record.url?scp=82955187838&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0027864
DO - 10.1371/journal.pone.0027864
M3 - Article
C2 - 22174752
AN - SCOPUS:82955187838
SN - 1932-6203
VL - 6
JO - PLoS ONE
JF - PLoS ONE
IS - 12
M1 - e27864
ER -