Brief report: Circulating markers of fibrosis are associated with immune reconstitution status in HIV-infected men

F. A. Tobolowsky, N. Wada, O. Martinez-Maza, L. Magpantay, S. L. Koletar, F. J. Palella, T. T. Brown, J. E. Lake

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Abstract

Introduction 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/mm3 were defined as immunologic non-responders (n = 25). Age-/race-matched men with post-ART CD4 >500 cells/mm3 served as controls (n = 49). HA and CXCL4 concentrations were measured via ELISA. Results Median pre-ART CD4 was 297 cells/mm3 for non-responders vs 386 cells/mm3 for controls. Median post-ART CD4 was 141 cells/mm3 for non-responders and 815 cells/mm3 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.

Original languageEnglish (US)
Article numbere0191606
JournalPloS one
Volume13
Issue number1
DOIs
StatePublished - Jan 2018

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

Tobolowsky, F. A., Wada, N., Martinez-Maza, O., Magpantay, L., Koletar, S. L., Palella, F. J., Brown, T. T., & Lake, J. E. (2018). Brief report: Circulating markers of fibrosis are associated with immune reconstitution status in HIV-infected men. PloS one, 13(1), [e0191606]. https://doi.org/10.1371/journal.pone.0191606