HIV-Specific, Ex Vivo Expanded T Cell Therapy: Feasibility, Safety, and Efficacy in ART-Suppressed HIV-Infected Individuals

Mol Ther. 2018 Oct 3;26(10):2496-2506. doi: 10.1016/j.ymthe.2018.08.015. Epub 2018 Sep 21.


Adoptive T cell therapy has had dramatic successes in the treatment of virus-related malignancies and infections following hematopoietic stem cell transplantation. We adapted this method to produce ex vivo expanded HIV-specific T cells (HXTCs), with the long-term goal of using HXTCs as part of strategies to clear persistent HIV infection. In this phase 1 proof-of-concept study (NCT02208167), we administered HXTCs to antiretroviral therapy (ART)-suppressed, HIV-infected participants. Participants received two infusions of 2 × 107 cells/m2 HXTCs at a 2-week interval. Leukapheresis was performed at baseline and 12 weeks post-infusion to measure the frequency of resting cell infection by the quantitative viral outgrowth assay (QVOA). Overall, participants tolerated HXTCs, with only grade 1 adverse events (AEs) related to HXTCs. Two of six participants exhibited a detectable increase in CD8 T cell-mediated antiviral activity following the two infusions in some, but not all, assays. As expected, however, in the absence of a latency reversing agent, no meaningful decline in the frequency of resting CD4 T cell infection was detected. HXTC therapy in ART-suppressed, HIV-infected individuals appears safe and well tolerated, without any clinical signs of immune activation, likely due to the low residual HIV antigen burden present during ART.

Keywords: HIV; cell therapy; latency.

Publication types

  • Clinical Trial, Phase I
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antiretroviral Therapy, Highly Active / methods*
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Cell- and Tissue-Based Therapy*
  • Female
  • Genetic Therapy
  • HIV Infections / genetics
  • HIV Infections / immunology
  • HIV Infections / therapy*
  • HIV Infections / virology
  • HIV-1 / immunology
  • HIV-1 / pathogenicity
  • Humans
  • Male
  • Middle Aged
  • T-Lymphocytes / immunology
  • T-Lymphocytes / transplantation*
  • Virus Activation / genetics
  • Virus Activation / immunology
  • Virus Replication / genetics
  • Virus Replication / immunology

Associated data