Correction: Effects of Combined CCR5/Integrase Inhibitors-Based Regimen on Mucosal Immunity in HIV-Infected Patients Naïve to Antiretroviral Therapy: A Pilot Randomized Trial

RESEARCH ARTICLE Effects of Combined CCR5/Integrase Inhibitors-Based Regimen on Mucosal Immunity in HIV-Infected Patients Naive to Antiretroviral Therapy: A Pilot Randomized Trial Sergio Serrano-Villar 1☯ , Talia Sainz 2☯ , Zhong-Min Ma 3 , Netanya S. Utay 4 , Tae Wook-Chun 5 , Surinder Mann 6 , Angela D. Kashuba 7 , Basile Siewe 8 , Anthony Albanese 9 , Paolo Troia- Cancio 6 , Elizabeth Sinclair 10 , Anoma Somasunderam 4 , Tammy Yotter 6 , Steven G. Deeks 10 , Alan Landay 8 , Richard B. Pollard 6 , Christopher J. Miller 3,6 , Santiago Moreno 1 , David M. Asmuth 6 * OPEN ACCESS Citation: Serrano-Villar S, Sainz T, Ma Z-M, Utay NS, Wook-Chun T, Mann S, et al. (2016) Effects of Combined CCR5/Integrase Inhibitors-Based Regimen on Mucosal Immunity in HIV-Infected Patients Naive to Antiretroviral Therapy: A Pilot Randomized Trial. PLoS Pathog 12(1): e1005381. doi:10.1371/journal. ppat.1005381 Editor: Guido Silvestri, Emory University, UNITED STATES Received: July 25, 2015 Accepted: December 11, 2015 Published: January 21, 2016 Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication. Data Availability Statement: All data are contained in the manuscript and supplemental material. Funding: This research was made possible by Grant Number UL1 RR024146 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH), NIH Roadmap for Medical Research, and by a grant from Pfizer Investigator Initiated Research Program, the UCSF/ Gladstone Institute of Virology & Immunology CFAR (grant number P30 AI027763), and the UNC CFAR (P30 AI50410). SSV is funded by a grant from the 1 University Hospital Ramon y Cajal, Madrid, Spain, 2 University Hospital La Paz, Madrid, Spain, 3 California National Primate Research Center, Davis, California, United States of America, 4 University of Texas Medical Branch, Galveston, Texas, United States of America, 5 Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, United States of America, 6 University of California Davis Medical Center, Sacramento, California, United States of America, 7 University of North Carolina School of Medicine, Chapel Hill, North Carolina, United States of America, 8 Rush University, Chicago, Illinois, United States of America, 9 Veterans Administration Northern California Health Care System, Mather, California, United States of America, 10 University of California San Francisco, San Francisco, California, United States of America ☯ These authors contributed equally to this work. * dasmuth@ucdavis.edu Abstract Whether initiation of antiretroviral therapy (ART) regimens aimed at achieving greater con- centrations within gut associated lymphoid tissue (GALT) impacts the level of mucosal immune reconstitution, inflammatory markers and the viral reservoir remains unknown. We included 12 HIV- controls and 32 ART-naive HIV patients who were randomized to efavir- enz, maraviroc or maraviroc+raltegravir, each with fixed-dose tenofovir disoproxil fumarate/ emtricitabine. Rectal and duodenal biopsies were obtained at baseline and at 9 months of ART. We performed a comprehensive assay of T-cell subsets by flow cytometry, T-cell den- sity in intestinal biopsies, plasma and tissue concentrations of antiretroviral drugs by high- performance liquid chromatography/mass spectroscopy, and plasma interleukin-6 (IL-6), lipoteichoic acid (LTA), soluble CD14 (sCD14) and zonulin-1 each measured by ELISA. Total cell-associated HIV DNA was measured in PBMC and rectal and duodenal mononu- clear cells. Twenty-six HIV-infected patients completed the follow-up. In the duodenum, the quadruple regimen resulted in greater CD8 + T-cell density decline, greater normalization of mucosal CCR5 + CD4 + T-cells and increase of the naive/memory CD8 + T-cell ratio, and a greater decline of sCD14 levels and duodenal HIV DNA levels (P = 0.004 and P = 0.067, respectively), with no changes in HIV RNA in plasma or tissue. Maraviroc showed the PLOS Pathogens | DOI:10.1371/journal.ppat.1005381 January 21, 2016