IP-10 and MIG are sensitive markers of early virological response to HIV-1 integrase inhibitors

Front Immunol. 2023 Oct 18:14:1257725. doi: 10.3389/fimmu.2023.1257725. eCollection 2023.

Abstract

Background: Interferon-inducible protein-10 (IP-10) and monokine induced by interferon-gamma (MIG) are chemokines recognized as inflammatory biomarkers during HIV-1 infection. We assessed their early and long-term dynamics after initiation of antiretroviral treatment (ART).

Methods: Persons with HIV-1 (PWH) aged>18 years starting their first ART in 2015-2021 in a prospective cohort (n=73) were included. IP-10 and MIG plasma levels were quantified using a multiplexed bead-based assay.

Results: IP-10 and MIG plasma levels showed a significant and consistent reduction following ART (80% integrase inhibitor [INSTI]-based) initiation, starting at day 20 and maintained throughout the study period (48 months), paralleling the HIV-1 RNA decay and CD4+ count recovery (p<0·001). At baseline, PWH≥ 50 years, CDC stage C and CD4+ count<350cells/mm3 had higher levels of IP-10 (p=0·022, p=0·001 and p=0·002, respectively) and MIG (p<0·001, p=0·024 and p=0·069, respectively). All of them matched their counterparts several months following ART initiation. MIG levels showed a greater decrease at day 10 in those treated with INSTI (p=0·038). Low-level HIV-1 viremia did not impact MIG or IP-10 levels.

Conclusion: Plasma IP-10 and MIG showed an early significant decline following ART initiation, with greater early declines in MIG levels in INSTI-based regimens. These findings suggest a strong impact of HIV-1 viremia on IP-10 and MIG levels.

Keywords: HIV-1 viral decay; IP-10; MIG; antiretroviral treatment; biomarkers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chemokine CXCL10
  • HIV Integrase Inhibitors* / pharmacology
  • HIV Integrase Inhibitors* / therapeutic use
  • HIV-1*
  • Humans
  • Interferon-gamma / pharmacology
  • Prospective Studies
  • Viremia

Substances

  • Interferon-gamma
  • Chemokine CXCL10
  • HIV Integrase Inhibitors

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This study has been funded by Instituto de Salud Carlos III [PI16/02159, BA18/00034, PI19/00747, PI22/01341, CM20/00243] and cofunded by the European Regional Development Fund, “A way to make Europe”; Red Española de Investigación en SIDA; Xunta de Galicia-Axencia Galega de Innovación (IN606A-2022/019); INVESTIGO Next GenerationEU Program TR349V-2022-10000052-00; Intramural Grant Program Galicia Sur Health Research Institute (CI22-A-2).