Impact of intensified antiretroviral therapy during early HIV infection on gut immunology and inflammatory blood biomarkers. (17th July 2017)

• Record Type: Journal Article
• Authors: Kim, Connie J.; Rousseau, Rodney; Huibner, Sanja; Kovacs, Colin; Benko, Erika; Shahabi, Kamnoosh; Kandel, Gabor; Ostrowski, Mario; Kaul, Rupert
• Is Part Of: AIDS. Volume 31:Number 11(2017)
• Publication Date: 2017-07-17
• Subjects: blood biomarkers -- CD4+ immunology -- CD4+ T cells -- early HIV infection -- early treatment -- gut immunology -- inflammation -- intensified antiretroviral treatment -- microbial translocation -- mucosal immunology -- randomized controlled trial; AIDS (Disease) -- Periodicals; Acquired Immunodeficiency Syndrome; AIDS (Disease); Periodicals; Periodicals; 616.9792005
• DOI: 10.1097/QAD.0000000000001515
• Languages: English
• ISSNs: 0269-9370

Abstract

Abstract : Objective: Standard antiretroviral therapy (ART) is slow to reverse gut mucosal immune defects that cause persistent inflammation and immune activation. We examined whether intensifying early-administered ART through the addition of maraviroc and raltegravir would accelerate their resolution. Design: ART-naïve men with early HIV infection were randomized in a double-blind manner to receive ART (emtricitabine/tenofovir disoproxil fumarate + lopinavir/ritonavir), together with either combined placebo or raltegravir + maraviroc, for 48 weeks. In a predefined substudy, paired blood and sigmoid biopsies were collected at baseline and week 48. Mucosal CD4 + T-cell immune subsets (Th1, Th17, and Th22 cells), CD8 + T-cell immune activation, and soluble blood markers of inflammation (IL-6, IL-17, macrophage inflammatory protein-1b, soluble CD14, and IL-10) and coagulation (D-dimer) were measured. Results: A total of 22 participants were enrolled, a median of 4 months after HIV acquisition. At baseline, there was substantial systemic and mucosal immune activation, and gut CD4 + T-cell numbers, Th22 cell numbers, and Th17 cell function were reduced compared with controls. Early ART restored gut Th22 numbers, improved but did not restore overall CD4 + numbers, and had no impact on Th17 function. Plasma levels of soluble CD14 and D-dimer normalized, whereas other inflammatory cytokines were reduced but not normalized. ART intensification had no impact on any blood or gut immune parameters. Conclusion: Early HIV infection causes substantial mucosal and systemic immune activation, and gut CD4 + T-cell dysfunction. One year of ART improved but did not normalize most parameters, regardless of intensification with raltegravir and maraviroc, and did not restore mucosal Th17 function. Abstract : Supplemental Digital Content is available in the text