TY - JOUR
T1 - Evidence that intermittent structured treatment interruption, but not immunization with ALVAC-HIV vCP1452, promotes host control of HIV replication
T2 - The results of AIDS Clinical Trials Group 5068
AU - Jacobson, Jeffrey M.
AU - Bucy, R. Pat
AU - Spritzler, John
AU - Saag, Michael S.
AU - Eron, Joseph J.
AU - Coombs, Robert W.
AU - Wang, Rui
AU - Fox, Lawrence
AU - Johnson, Victoria A.
AU - Cu-Uvin, Susan
AU - Cohn, Susan E.
AU - Mildvan, Donna
AU - O'Neill, Dorothy
AU - Janik, Jennifer
AU - Purdue, Lynette
AU - O'Connor, Deborah K.
AU - Di Vita, Christine
AU - Frank, Ian
N1 - Funding Information:
We are indebted to Gwen Marshall and J. Darren Hazelwood, for technical support; to the clinicians who referred patients to the study; and to the patients who participated. Financial support was provided by the following organizations: the Adult AIDS Clinical Trials Group (AACTG), funded by the National Institute of Allergy and Infectious Diseases (grant AI38858); the Statistical Data and Analysis Center (grant AI38855); the Adult AIDS Clinical Trials Units (grants AI46381, AI27665, AI25879, AI27658, AI25868, AI50410, AI46370, AI25924, AI27664, AI25903, and AI32783); and the General Clinical Research Center Units, funded by the National Center for Research Resources (grants RR00096, RR00044, RR00046, RR00032, and RR00040). V.A.J.’s virology laboratory was supported in part by the AACTG; by virology support funding from the National Institute of Allergy and Infectious Diseases and the AACTG Cen- tral Group Grant (grants U01AI38858 and P30 AI27767); by the University of Pennsylvania Center for AIDS Research; and by the Birmingham Veterans Administration Medical Center and University of Alabama, Birmingham, Centers for AIDS Research core clinic and laboratory facilities.
PY - 2006/9/1
Y1 - 2006/9/1
N2 - Background. The ability to control human immunodeficiency virus (HIV) replication in vivo in the absence of antiretroviral therapy (ART) is a measure of the efficiency of antiviral immunity. In a study of patients with chronic, ART-suppressed HIV infection, AIDS Clinical Trials Group 5068 investigated the effects of immunization with an exogenous HIV vaccine and pulse exposure to the subject's unique viral epitopes, by means of structured treatment interruptions (STIs), on the dynamics of viral rebound during a subsequent analytical treatment inter-ruption (ATI). Methods. Ninety-seven subjects receiving stable ART with an HIV-1 RNA load <50 copies/mL and CD4+ T lymphocyte count >400 cells/mm3 were randomized to undergo continued ART, STIs, ALVAC-HIV vCP1452 immunization, or STIs and ALVAC-HIV vCP1452 immunization. Results. Subjects in the 2 STI arms had a significantly longer median doubling time in the period of the initial rise of viral load, a significantly lower median peak viral load, a significantly lower median end-of-ATI viral load set point, and a greater proportion of subjects with an end-of-ATI viral load set point <1000 copies/mL, compared with the subjects in the 2 arms without STIs. With an immunization schedule of 3 sets of 3 weekly injections, ALVAC-HIV VCP1452 did not affect viral load measures. Conclusions. In this randomized, controlled study of intermittent STI as a therapeutic autoimmunization strategy, evidence of enhanced immunologic control of HIV replication was demonstrated.
AB - Background. The ability to control human immunodeficiency virus (HIV) replication in vivo in the absence of antiretroviral therapy (ART) is a measure of the efficiency of antiviral immunity. In a study of patients with chronic, ART-suppressed HIV infection, AIDS Clinical Trials Group 5068 investigated the effects of immunization with an exogenous HIV vaccine and pulse exposure to the subject's unique viral epitopes, by means of structured treatment interruptions (STIs), on the dynamics of viral rebound during a subsequent analytical treatment inter-ruption (ATI). Methods. Ninety-seven subjects receiving stable ART with an HIV-1 RNA load <50 copies/mL and CD4+ T lymphocyte count >400 cells/mm3 were randomized to undergo continued ART, STIs, ALVAC-HIV vCP1452 immunization, or STIs and ALVAC-HIV vCP1452 immunization. Results. Subjects in the 2 STI arms had a significantly longer median doubling time in the period of the initial rise of viral load, a significantly lower median peak viral load, a significantly lower median end-of-ATI viral load set point, and a greater proportion of subjects with an end-of-ATI viral load set point <1000 copies/mL, compared with the subjects in the 2 arms without STIs. With an immunization schedule of 3 sets of 3 weekly injections, ALVAC-HIV VCP1452 did not affect viral load measures. Conclusions. In this randomized, controlled study of intermittent STI as a therapeutic autoimmunization strategy, evidence of enhanced immunologic control of HIV replication was demonstrated.
UR - http://www.scopus.com/inward/record.url?scp=33748078472&partnerID=8YFLogxK
U2 - 10.1086/506364
DO - 10.1086/506364
M3 - Article
C2 - 16897661
AN - SCOPUS:33748078472
SN - 0022-1899
VL - 194
SP - 623
EP - 632
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 5
ER -