Open AccessBrief report: Circulating markers of fibrosis are associated with immune reconstitution status in HIV-infected men
Author(s) -
Farrell Tobolowsky,
Nikolas Wada,
O. Martínez-Maza,
Larry Magpantay,
Susan L. Koletar,
Frank J. Palella,
Thomas R. Brown,
Jordan E. Lake
Publication year - 2018
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0191606
Subject(s) - immune system , medicine , immunology , hyaluronic acid , human immunodeficiency virus (hiv) , viral load , antiretroviral therapy , gastroenterology , anatomy
Lymphoid tissue fibrosis may contribute to incomplete immune reconstitution on antiretroviral therapy (ART) via local CD4 + T lymphocyte (CD4) depletion. Hyaluronic acid (HA) increases with fibrotic burden. CXCL4 concentrations increase in response to pro-fibrotic stimuli, but lower CXCL4 concentrations in HIV-infected individuals may reflect successful immune evasion by HIV. We investigated relationships between circulating HA and CXCL4 concentrations and immune reconstitution on ART in HIV-infected Multicenter AIDS Cohort Study participants. Methods HIV-infected men on ART for >1 year with cryopreserved plasma samples and suppressed post-ART HIV-1 RNA were included. Men with post-ART CD4 <200 cells/mm 3 were defined as immunologic non-responders (n = 25). Age-/race-matched men with post-ART CD4 >500 cells/mm 3 served as controls (n = 49). HA and CXCL4 concentrations were measured via ELISA. Results Median pre-ART CD4 was 297 cells/mm 3 for non-responders vs 386 cells/mm 3 for controls. Median post-ART CD4 was 141 cells/mm 3 for non-responders and 815 cells/mm 3 for controls. HIV infection duration was 23 years, with median time on ART 13 years for non-responders vs 11 years for controls. Pre-ART HA and CXCL4 concentrations did not vary by eventual immune reconstitution status. Post-ART HA concentrations tended to be higher (85 vs 36 ng/mL, p = 0.07) and CXCL4 concentrations were lower (563 vs 1459 ng/mL, p = 0.01) among non-responders. Among men with paired pre-/post-ART samples, non-responders had greater HA increases and CXCL4 decreases than controls (HA: 50 vs 12 ng/mL, p = 0.04; CXCL4: -1258 vs -405 ng/mL, p = 0.01). Conclusions Higher circulating concentrations of HA and lower concentrations of CXCL4 are associated with failure of immune reconstitution on ART.