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Abstract
Background
Long-term treatment of primary HIV-1 infection (PHI) may allow the immune reconstitution
of responses lost during the acute viremic phase and decrease of peripheral reservoirs.
This in turn may represent the best setting for the use of therapeutic vaccines in
order to lower the viral set-point or control of viral rebound upon ART discontinuation.
Methods
We investigated a cohort of 16 patients who started ART at PHI, with treatment duration
of ≥4 years and persistent aviremia (<50 HIV-1 copies/ml). The cohort was characterized
in terms of viral subtype, cell-associated RNA, proviral DNA and HLA genotype. Secretion
of IFN-γ, IL-2 and TNF-α by CD8 T-cells was analysed by polychromatic flowcytometry
using a panel of 192 HIV-1-derived epitopes.
Results
This cohort is highly homogenous in terms of viral subtype: 81% clade B. We identified
44 epitope-specific responses: all patients had detectable responses to >1 epitope
and the mean number of responding epitopes per patient was 3. The mean frequency of
cytokines-secreting CD8 T-cells was 0.32%. CD8 T-cells secreting simultaneously IFN-γ,
IL-2 and TNF-α made up for about 40% of the response and cells secreting at least
2 cytokines for about 80%, consistent with a highly polyfunctional CD8 T-cell profile.
There was no difference in term of polyfunctionality when HLA restriction, or recognized
viral regions and epitopes were considered. Proviral DNA was detectable in all patients
but at low levels (mean = 108 copies/1 million PBMCs) while cell-associated mRNA was
not detectable in 19% of patients (mean = 11 copies/1 million PBMCs when detectable).
Conclusion
Patients with sustained virological suppression after initiation of ART at PHI show
polyfunctional CD8 T-cell and low levels of proviral DNA with an absence of residual
replication in a substantial percentage of patients. The use of therapeutic vaccines
in this population may promote low level of rebound viremia or control of viral replication
upon ART cessation.