Therapeutic immunisation plus cytokine and hormone therapy improves CD4 T-cell counts, restores anti-HIV-1 responses and reduces immune activation in treated chronic HIV-1 infection

Vaccine. 2014 Dec 5;32(51):7005-7013. doi: 10.1016/j.vaccine.2014.09.072. Epub 2014 Oct 22.


Background: This randomised, open label, phase I, immunotherapeutic study investigated the effects of interleukin (IL)-2, granulocyte-macrophage colony-stimulating factor (GM-CSF), recombinant human growth hormone (rhGH), and therapeutic immunisation (a Clade B DNA vaccine) on combination antiretroviral therapy (cART)-treated HIV-1-infected individuals, with the objective to reverse residual T-cell dysfunction.

Methods: Twelve HIV-1(+) patients on suppressive cART with baseline CD4 T-cell counts >400 cells/mm(3) blood were randomised into one of three groups: (1) vaccine, IL-2, GM-CSF and rhGH (n=3); (2) vaccine alone (n=4); or (3) IL-2, GM-CSF and rhGH (n=5). Samples were collected at weeks 0, 1, 2, 4, 6, 8, 12, 16, 24 and 48. Interferon (IFN)-γ, IL-2, IL-4 and perforin ELISpot assays performed at each time point quantified functional responses to Gag p17/p24, Nef, Rev, and Tat peptides; and detailed T-cell immunophenotyping was undertaken by flow cytometry. Proviral DNA was also measured.

Results: Median baseline CD4 T-cell count was 757 cells/mm(3) (interquartile range [IQR] 567-886 cells/mm(3)), median age 48 years (IQR 42-51 years), and plasma HIV-1-RNA <50 copies/ml for all subjects. Patients who received vaccine plus IL-2, GM-CSF and rhGH (group 1) showed the most marked changes. Assessing mean changes from baseline to week 48 revealed significantly elevated numbers of CD4 T cells (p=0.0083) and improved CD4/CD8 T-cell ratios (p=0.0033). This was accompanied by a significant reduction in expression of CD38 on CD4 T cells (p=0.0194), significantly increased IFN-γ and IL-2 production in response to Gag (p=0.0122) and elevated IFN-γ production in response to Tat (p=0.041) at week 48 compared to baseline. Subjects in all treatment groups showed significantly reduced PD-1 expression at week 48 compared to baseline, with some reductions in proviral DNA.

Conclusions: Multifarious immunotherapeutic approaches in the context of fully suppressive cART further reduce immune activation, and improve both CD4 T-lymphocyte counts and HIV-1-specific T-cell responses (NCT01130376).

Keywords: DNA vaccine; HIV-1; Immune-based therapy.

Publication types

  • Clinical Trial, Phase I
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • AIDS Vaccines / therapeutic use*
  • Adult
  • Anti-Retroviral Agents / therapeutic use*
  • CD4-Positive T-Lymphocytes / immunology
  • Combined Modality Therapy / methods
  • Cytokines / analysis
  • Cytokines / therapeutic use*
  • Enzyme-Linked Immunospot Assay
  • Flow Cytometry
  • Growth Hormone / therapeutic use*
  • HIV Antigens / immunology
  • HIV Infections / immunology*
  • HIV Infections / therapy*
  • Humans
  • Immunophenotyping
  • Lymphocyte Activation
  • Male
  • Middle Aged
  • Perforin / analysis
  • Proviruses / genetics
  • Treatment Outcome
  • Vaccines, DNA / therapeutic use


  • AIDS Vaccines
  • Anti-Retroviral Agents
  • Cytokines
  • HIV Antigens
  • Vaccines, DNA
  • Perforin
  • Growth Hormone

Associated data