Early and delayed benefits of HIV-1 suppression: timeline of recovery of innate immunity effector cells.
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OBJECTIVE: The kinetics of recovery for innate immune effectors following antiretroviral therapy are unknown. DESIGN AND 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, L., Chehimi, J., Zhou, L., Foulkes, A. S., June, R., Maino, V. C., ... Montaner, L. J.
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Azzoni, Livio||Chehimi, Jihed||Zhou, Lan||Foulkes, Andrea S||June, Rayford||Maino, Vernon C||Landay, Alan||Rinaldo, Charles||Jacobson, Lisa P||Montaner, Luis J
