Changes in gastrointestinal microbial communities influence HIV-specific CD8+ T-cell responsiveness to immune checkpoint blockade

AIDS. 2020 Aug 1;34(10):1451-1460. doi: 10.1097/QAD.0000000000002557.


Objectives: The aim of this study was to examine the relationship between gut microbial communities in HIV-infected individuals on suppressive antiretroviral therapy (cART), and the peripheral HIV-Gag-specific CD8 T-cell responses before and after ex-vivo immune checkpoint blockade (ICB).

Design: Thirty-four HIV-seropositive, 10 HIV-seronegative and 12 HIV-seropositive receiving faecal microbiota transplant (FMT) participants were included. Gut microbial communities, peripheral and gut associated negative checkpoint receptors (NCRs) and peripheral effector functions were assessed.

Methods: Bacterial 16s rRNA sequencing for gut microbiome study and flow-based assays for peripheral and gut NCR and their cognate ligand expression, including peripheral HIV-Gag-specific CD8 T-cell responses before and after ex-vivo anti-PD-L1 and anti-TIGIT ICB were performed.

Results: Fusobacteria abundance was significantly higher in HIV-infected donors compared to uninfected controls. In HIV-infected participants receiving Fusobacteria-free FMT, Fusobacteria persisted up to 24 weeks in stool post FMT. PD-1 TIGIT and their ligands were expanded in mucosal vs. peripheral T cells and dendritic cells, respectively. PD-L1 and TIGIT blockade significantly increased the magnitude of peripheral anti-HIV-Gag-specific CD8 T-cell responses. Higher gut Fusobacteria abundance was associated with lower magnitude of peripheral IFN-γ+ HIV-Gag-specific CD8 T-cell responses following ICB.

Conclusion: The gut colonization of Fusobacteria in HIV infection is persistent and may influence anti-HIV T-cell immunity to PD-1 or TIGIT blockade. Strategies modulating Fusobacteria colonization may elicit a favourable mucosal immune landscape to enhance the efficacy of ICB for HIV cure.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Anti-HIV Agents / therapeutic use
  • CD8-Positive T-Lymphocytes / drug effects*
  • Fecal Microbiota Transplantation
  • Female
  • Fusobacteria / isolation & purification
  • Gastrointestinal Microbiome*
  • HIV Infections / drug therapy
  • HIV Infections / microbiology*
  • Humans
  • Immune Checkpoint Inhibitors / therapeutic use*
  • Male
  • Middle Aged
  • RNA, Ribosomal, 16S / genetics
  • Sexual and Gender Minorities


  • Anti-HIV Agents
  • Immune Checkpoint Inhibitors
  • RNA, Ribosomal, 16S