title: Apoptosis and proliferation kinetics of T cells in patients having experienced antiretroviral treatment interruptions.
abstract: Multiple failures of antiretroviral treatments, as a result of multidrug-resistant virus, have led to a proposal for structured therapeutic interruptions (STI). However, a significant decrease in CD4+ T cells may occur. The aim of our study was to determine the kinetics of T cell subpopulation changes, T cell apoptosis and peripheral blood mononuclear cell proliferation after STI. The impact of resistance mutation disappearance on T cell apoptosis was also studied. Ten patients were enrolled prospectively, and blood sampling was performed at weeks 0, 2, 4, 6, 8 and 12. The mean increase in viral load was 1.3 log(10) copies/ml, ranging from 0.1 to 3.2. CD4+ T cell count decreased to a mean of 80 cells/mm(3) from baseline to week 12. In the same period, CD8+ T cells decreased to a mean of 139 cells/mm(3). A significant increase in both T cell apoptosis and proliferation of mononuclear cells was observed. However, proliferation was an early and brief event. The increase in CD4+ T cell apoptosis was obvious in patients exhibiting complete reversion of resistance mutations to antiviral drugs. Our results suggest that during STI, apoptosis is an overwhelming phenomenon compared with proliferation, and may explain the limited immunological impact of this therapeutic option.
authors.affiliation: Service des Maladies Infectieuses et Tropicales, Hôpital de l'Archet 1, Centre Hospitalo-Universitaire de Nice, BP3079, 06202, Nice cedex 3, France. roger.pm@chu-nice.fr
authors.forename: Pierre-Marie
authors.initials: PM
authors.lastname: Roger
authors.forename: Jacques
authors.initials: J
authors.lastname: Durant
authors.forename: Michel
authors.initials: M
authors.lastname: Ticchioni
authors.forename: Philippe
authors.initials: P
authors.lastname: Halfon
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Breittmayer
authors.forename: Christelle
authors.initials: C
authors.lastname: Brignone
authors.forename: Sylvie
authors.initials: S
authors.lastname: Chaillou
authors.forename: Brigitte
authors.initials: B
authors.lastname: Dunais
authors.forename: Pierre
authors.initials: P
authors.lastname: Dellamonica
authors.forename: Alain
authors.initials: A
authors.lastname: Bernard
mesh_terms: D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects*; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D004334:Drug Administration Schedule; D006801:Humans; D008137:Longitudinal Studies; D011446:Prospective Studies; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*