BACKGROUND/AIMS: Lamivudine therapy in patients with chronic hepatitis B can induce the recovery of antiviral T cell responses. It is unknown whether the recovery of T cell responsiveness is long-lasting and persists throughout the treatment and whether the elevation of viremia which follows therapy withdrawal can restore a condition of T cell unresponsiveness. METHODS: Frequency and function of circulating hepatitis B virus (HBV)-specific CD4 and CD8 cells from 12 hepatitis e surface antigen + patients with chronic hepatitis B were studied longitudinally before, during and after lamivudine therapy by intracellular cytokine staining, proliferation and cytotoxicity assays against HBV proteins and peptides. CD4-mediated responses were analyzed in all patients, whereas CD8 cells were studied in 6 HLA-A2+ patients. RESULTS: HBV-specific CD4 and CD8 reactivity showed a bi-phasic behavior under lamivudine therapy with an early enhancement of T cell frequency and intensity of responses followed by a persistent decline starting from the 5th to 6th month of treatment. CONCLUSIONS: Since restoration of HBV-specific T cell reactivity is only transient, our study indicates that therapeutic stimulation of HBV-specific T cell responses to complement lamivudine treatment should be done early after the initiation of lamivudine. Moreover, the transient nature of the immune reconstitution may represent a favorable condition for virus reactivation once lamivudine therapy is withdrawn.
BACKGROUND/AIMS: Lamivudine therapy in patients with chronic hepatitis B can induce the recovery of antiviral T cell responses. It is unknown whether the recovery of T cell responsiveness is long-lasting and persists throughout the treatment and whether the elevation of viremia which follows therapy withdrawal can restore a condition of T cell unresponsiveness. METHODS: Frequency and function of circulating hepatitis B virus (HBV)-specific CD4 and CD8 cells from 12 hepatitis e surface antigen + patients with chronic hepatitis B were studied longitudinally before, during and after lamivudine therapy by intracellular cytokine staining, proliferation and cytotoxicity assays against HBV proteins and peptides. CD4-mediated responses were analyzed in all patients, whereas CD8 cells were studied in 6 HLA-A2+ patients. RESULTS:HBV-specific CD4 and CD8 reactivity showed a bi-phasic behavior under lamivudine therapy with an early enhancement of T cell frequency and intensity of responses followed by a persistent decline starting from the 5th to 6th month of treatment. CONCLUSIONS: Since restoration of HBV-specific T cell reactivity is only transient, our study indicates that therapeutic stimulation of HBV-specific T cell responses to complement lamivudine treatment should be done early after the initiation of lamivudine. Moreover, the transient nature of the immune reconstitution may represent a favorable condition for virus reactivation once lamivudine therapy is withdrawn.
Authors: Laura Rivino; Nina Le Bert; Upkar S Gill; Kamini Kunasegaran; Yang Cheng; Damien Zm Tan; Etienne Becht; Navjyot K Hansi; Graham R Foster; Tung-Hung Su; Tai-Chung Tseng; Seng Gee Lim; Jia-Horng Kao; Evan W Newell; Patrick Tf Kennedy; Antonio Bertoletti Journal: J Clin Invest Date: 2018-01-08 Impact factor: 14.808
Authors: Helen Cooksley; Shilpa Chokshi; Yafit Maayan; Heiner Wedemeyer; Pietro Andreone; Richard Gilson; Thomas Warnes; Simona Paganin; Fabien Zoulim; David Frederick; Avidan U Neumann; Carol L Brosgart; Nikolai V Naoumov Journal: Antimicrob Agents Chemother Date: 2007-11-05 Impact factor: 5.191
Authors: Amy C Sherman; Nirupama Trehanpati; Marybeth Daucher; Richard T Davey; Henry Masur; Shiv Kumar Sarin; Shyam Kottilil; Anita Kohli Journal: AIDS Res Hum Retroviruses Date: 2013-02-11 Impact factor: 2.205