OBJECTIVE: To evaluate whether controlled re-exposures to autologous HIV-1 could boost HIV-specific immunity and limit virus replication in patients with chronic HIV-1 infection. PATIENTS AND DESIGN:Subjects with at least 2 years virus suppression during antiretroviral therapy and a CD4 : CD8 ratio >; 1 were randomly assigned to interrupt highly active antiretroviral treatment (HAART) three times (n = 12) or to continue their previous HAART (n = 14). RESULTS: In 10/12 interrupter patients a rebound of HIV-1 RNA was detected in all three structured treatment interruptions (STI). Plasma virus doubling time was shorter during the first STI than in the second and third STI, corresponding to an average 13% reduction in viral basic reproductive rate. However, the mean time before plasma viral load rose to > 50 copies/ml was significantly shorter in the second and third STI. The average frequency of HIV-specific CD8 T cells in the interrupter patients at the end of the third STI cycle was significantly higher compared with the baseline and the end of the first STI. A substantial increase in HIV-specific CD8 T cell frequencies was found in four interrupter patients, whereas there were no changes in all 14 non-interrupter individuals. A weak p24-specific T helper response developed in 5/12 interrupter patients compared with no response in non-interruptors, but these responses were transient and disappeared rapidly. CONCLUSION: The increase in the control of viral replication, and positive effects of STI on immune responses in this population should encourage the further development of HIV-specific immune-based therapeutic strategies.
RCT Entities:
OBJECTIVE: To evaluate whether controlled re-exposures to autologous HIV-1 could boost HIV-specific immunity and limit virus replication in patients with chronic HIV-1 infection. PATIENTS AND DESIGN: Subjects with at least 2 years virus suppression during antiretroviral therapy and a CD4 : CD8 ratio > 1 were randomly assigned to interrupt highly active antiretroviral treatment (HAART) three times (n = 12) or to continue their previous HAART (n = 14). RESULTS: In 10/12 interrupter patients a rebound of HIV-1 RNA was detected in all three structured treatment interruptions (STI). Plasma virus doubling time was shorter during the first STI than in the second and third STI, corresponding to an average 13% reduction in viral basic reproductive rate. However, the mean time before plasma viral load rose to > 50 copies/ml was significantly shorter in the second and third STI. The average frequency of HIV-specific CD8 T cells in the interrupter patients at the end of the third STI cycle was significantly higher compared with the baseline and the end of the first STI. A substantial increase in HIV-specific CD8 T cell frequencies was found in four interrupter patients, whereas there were no changes in all 14 non-interrupter individuals. A weak p24-specific T helper response developed in 5/12 interrupter patients compared with no response in non-interruptors, but these responses were transient and disappeared rapidly. CONCLUSION: The increase in the control of viral replication, and positive effects of STI on immune responses in this population should encourage the further development of HIV-specific immune-based therapeutic strategies.
Authors: Marcus Altfeld; Jan van Lunzen; Nicole Frahm; Xu G Yu; Claus Schneider; Robert L Eldridge; Margaret E Feeney; Dirk Meyer-Olson; Hans-Juergen Stellbrink; Bruce D Walker Journal: J Clin Invest Date: 2002-03 Impact factor: 14.808
Authors: Annette Oxenius; David A Price; Huldrych F Günthard; Sara J Dawson; Catherine Fagard; Luc Perrin; Marek Fischer; Rainer Weber; Montserrat Plana; Felipe García; Bernard Hirschel; Angela McLean; Rodney E Phillips Journal: Proc Natl Acad Sci U S A Date: 2002-10-07 Impact factor: 11.205
Authors: Rutao Luo; Lamont Cannon; Jason Hernandez; Michael J Piovoso; Ryan Zurakowski Journal: J Process Control Date: 2011-03-01 Impact factor: 3.666
Authors: Annette Oxenius; Angela R McLean; Marek Fischer; David A Price; Sarah J Dawson; Roland Hafner; Christine Schneider; Helen Joller; Bernard Hirschel; Rodney E Phillips; Rainer Weber; Huldrych F Günthard Journal: J Virol Date: 2002-10 Impact factor: 5.103
Authors: Xu G Yu; Marylyn M Addo; Eric S Rosenberg; William R Rodriguez; Paul K Lee; Cecily A Fitzpatrick; Mary N Johnston; Daryld Strick; Philip J R Goulder; Bruce D Walker; Marcus Altfeld Journal: J Virol Date: 2002-09 Impact factor: 5.103