A therapeutic HIV-1 vaccine reduces markers of systemic immune activation and latent infection in patients under highly active antiretroviral therapy

Vaccine. 2020 Jun 2;38(27):4336-4345. doi: 10.1016/j.vaccine.2020.04.015. Epub 2020 May 6.


HIV infection is characterized by chronic immune activation and the establishment of a pool of latently infected cells. Antiretroviral therapy (ART) can suppress viral load to undetectable levels in peripheral blood by standard measure, however immune activation/chronic inflammation and latent infection persist and affect quality of life. We have now shown that a novel therapeutic HIV vaccine consisting of replication-defective HIV (HIVAX), given in the context of viral suppression under ART, can reduce both immune activation/chronic inflammation and latent infection. Immune activation, as measured by percent of CD8 + HLA-DR + CD38 + T cells, approached levels of healthy controls at week 16 following vaccination. Reduced immune activation was accompanied by a reduction in pro-inflammatory cytokines and peripheral α4β7 + plasmacytoid DC (a marker of mucosal immune activation). Levels of both HIV-1 DNA and 2-LTR circles were reduced at week 16 following vaccination, suggesting HIVAX can impact HIV-1 latency and reduce viral replication. Surprisingly, reduced immune activation/chronic inflammation was accompanied by an increase in the percent of memory CD4 + T cells expressing markers PD-1 and TIM-3. In addition, evaluation of HIV-1 Gag-specific CD4 + T cells for expression of 96 T cell related genes pre- and post-therapy revealed increased expression of a number of genes involved in the regulation of immune activation, T cell activation, and antiviral responses. Overall this study provides evidence that vaccination with HIVAX in subjects under long term antiviral suppression can reduce immune activation/chronic inflammation and latent infection (Clinicaltrials.gov, identifier NCT01428596).

Keywords: HIV-1; Immune activation; Immune responses; Latent viral infection; T-cell activation; Therapeutic vaccine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiretroviral Therapy, Highly Active
  • CD4-Positive T-Lymphocytes
  • CD8-Positive T-Lymphocytes
  • HIV Infections* / drug therapy
  • HIV-1*
  • Humans
  • Latent Infection*
  • Lymphocyte Activation
  • Quality of Life
  • Viral Load

Associated data

  • ClinicalTrials.gov/NCT01428596