Limited long‐term naive CD4⁺ T cell reconstitution in patients experiencing viral load rebounds during HAART

Abstract

Long-term (3.5 years) immune reconstitution in relation to viral load response was determined. Plasma HIV-1 RNA was suppressed in 40 patients (full responders) up to 42 months, and 17 patients achieved partial response. The measurements of CD4(+) and CD8(+) T lymphocyte subsets (CD45RA, CD45RACD62L, CD45RO, CD28, CD38) were carried out by flow cytometry. Full responders had a significant increase of CD4(+) and all CD4(+) T subsets both up to 6 and from 6 to 42 months, while the increase for partial responders was only up to 6 months. By 6 months, higher slopes were observed in full versus partial responders in the % of CD28 on CD4(+) and the % of CD4(+) memory subset and in both naïve and memory CD4(+) subsets from 6 to 42 months. The percentage of CD8(+) and its subsets was decreased significantly in full responders both up to 6 and from 6 to 42 months (except for an increase in the CD8(+)CD45RA(+) CD62L(+) cells), while in partial responders this decrease was only up to 6 months. Lower slopes were observed in full versus partial responders from 6 to 42 months in the percentages of CD8(+), CD8(+)CD45RO(+), CD8(+)CD28(-), and CD8(+)CD38(+) T cells. In conclusion, full responders have a stronger long-term naive CD4(+) T cell subset reconstitution than partial responders.

Antiretroviral Therapy‐Induced Dominant Interleukin‐2 HIV‐1 Gag CD4+ T Cell Response: Evidence of Functional Recovery of HIV‐1‐Specific CD4+ T Cells

“…Immune reconstitution remains a central goal in HIV therapy [18–20]. Studies in treated individuals indicate that prolonged antiretroviral treatment (ART) significantly changes the functionality of specific T cell responses [5, 14], but it is still not clear whether functional changes result from decreased viremia or they correspond to a true immune reconstitution.…”