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-α 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.
From the aThe Wistar Institute, Philadelphia, Pennsylvania
bDepartment of Statistics, Texas A&M University, College Station, Texas
cDivision of Biostatistics, University of Massachusetts School of Public Health and Health Sciences, Amherst, Massachusetts
dBiological Research and Development, BD Biosciences, San Jose, California
eDepartment of Immunology/Microbiology Rush University Medical Center, Chicago, Illinois
fDepartment of Infectious Diseases and Microbiology, University of Pittsburgh Graduate School of Public Health, Pittsburgh, Pennsylvania
gDepartment of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland.
*These authors contributed equally to the manuscript.
Received 5 July, 2006
Revised 9 October, 2006
Accepted 30 October, 2006
Correspondence to Luis Montaner, DVM, The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104, USA. E-mail: firstname.lastname@example.org