Early and delayed benefits of HIV-1 suppression: timeline of recovery of innate immunity effector cells.
OBJECTIVE
The kinetics of recovery for innate immune effectors following antiretroviral therapy are unknown.


METHODS
Multiple sequential cryopreserved samples (viremic and ART-suppressed) from 66 patients enrolled in the Women's Interagency HIV Study or Multicenter AIDS Cohort Study cohorts (median follow-up, 700 days) were analyzed to determine natural killer, dendritic and T-cell changes by flow cytometry. Functional parameters were also measured in a subset of samples. Changes over time were analyzed by mixed-effect modeling based on a linear spline with a single knot at 270 days.


RESULTS
Following viral suppression, a rapid rise in CD4 and white blood cell counts and a decline in T-cell activation were confirmed. However, natural killer cell subsets increased after 270 days of therapy, with a negative effect by baseline CD4%. CD123+ plasmacytoid but not myeloid dendritic cells showed a trend to increase during the first 270 days with a positive effect of baseline CD4%; plasmacytoid dendritic cell-induced interferon-alpha production significantly increased by end of follow-up.


CONCLUSIONS
The kinetics of natural killer and plasmacytoid dendritic cell recovery are markedly different from those of T-cell subsets, indicative of early and delayed benefits of suppressive regimens.
Azzoni
Livio
L
The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104, USA.
Chehimi
Jihed
J
Zhou
Lan
L
Foulkes
Andrea S
AS
June
Rayford
R
Maino
Vernon C
VC
Landay
Alan
A
Rinaldo
Charles
C
Jacobson
Lisa P
LP
Montaner
Luis J
LJ
D019380:Anti-HIV Agents / Q000627:therapeutic use; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology*; D015497:HIV-1; D006801:Humans; D007111:Immunity, Cellular; D007113:Immunity, Innate; D007694:Killer Cells, Natural / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013997:Time Factors
D019380:Anti-HIV Agents