Decay kinetics of human immunodeficiency virus-specific effector cytotoxic T lymphocytes after combination antiretroviral therapy

Abstract

Little is known of the changes in human immunodeficiency virus type 1 (HIV-1)-specific effector cytotoxic T lymphocytes (CTL) after potent antiretroviral therapy. Using HLA/peptide tetrameric complexes, we show that after starting treatment, there are early rapid fluctuations in the HIV-1-specific CTL response which last 1 to 2 weeks. These fluctuations are followed by an exponential decay (median half-life, 45 days) of HIV-1-specific CTL which continues while viremia remains undetectable. These data have implications for the immunological control of drug-resistant virus.

FIG. 1

Changes in HIV-specific CTLe frequencies in eight individuals (A to H). The percentages of CD8⁺ T cells staining with A2Gag (■), A2Pol (□), and B35Env (◊) are represented on the y axes and the x axes show the number of days after starting treatment. Patients G and H had high frequencies of HIV-specific CTL prior to treatment and therefore have larger-scaled axes than patients A to F. Note that for patients C and F, the first on-therapy time point measured was 1 day after treatment started.

FIG. 2

Late exponential decay of HIV-specific CTLe responses in four individuals. The patients and epitopes are identified on the right. Two responses were monitored in patient A, while one response was monitored in patients B, G, and H. The median half-life of the decay was 45 days.

FIG. 3

(A) Serial flow cytometry profiles of one individual after starting treatment with potent antiretrovirals. The CD8⁺ T-cell population is illustrated with CD38 expression along the x axes and B35Env tetramer staining along the y axes. The time after treatment and percentage of CD8⁺ T cells staining with the tetramer are documented in the top right-hand corner of each graph. The percentage of CD8⁺ T cells staining with the tetramer and the intensity with which the tetramer-positive cells stain with anti-CD38 antibodies declined after treatment started. (B) Changes in the percentage of CD8⁺ T cells staining with the B35Env tetramer to 600 days after treatment started. The decay half-life remained constant throughout the course of the study. (C) Decay in the staining of tetramer-positive cells with anti-CD38 antibodies. In the absence of detectable viremia, staining with anti-CD38 antibodies declined in intensity.