Evidence that intermittent structured treatment interruption, but not immunization with ALVAC-HIV vCP1452, promotes host control of HIV replication: The results of AIDS Clinical Trials Group 5068

Jeffrey M. Jacobson; R. Pat Bucy; John Spritzler; Michael S. Saag; Joseph J. Eron; Robert W. Coombs; Rui Wang; Lawrence Fox; Victoria A. Johnson; Susan Cu-Uvin; Susan E. Cohn; Donna Mildvan; Dorothy O'Neill; Jennifer Janik; Lynette Purdue; Deborah K. O'Connor; Christine Di Vita; Ian Frank

doi:10.1086/506364

Evidence that intermittent structured treatment interruption, but not immunization with ALVAC-HIV vCP1452, promotes host control of HIV replication: The results of AIDS Clinical Trials Group 5068

Jeffrey M. Jacobson^*, R. Pat Bucy, John Spritzler, Michael S. Saag, Joseph J. Eron, Robert W. Coombs, Rui Wang, Lawrence Fox, Victoria A. Johnson, Susan Cu-Uvin, Susan E. Cohn, Donna Mildvan, Dorothy O'Neill, Jennifer Janik, Lynette Purdue, Deborah K. O'Connor, Christine Di Vita, Ian Frank

^*Corresponding author for this work

Medicine, Infectious Diseases Division

Research output: Contribution to journal › Article › peer-review

80 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	623-632
Number of pages	10
Journal	Journal of Infectious Diseases
Volume	194
Issue number	5
DOIs	https://doi.org/10.1086/506364
State	Published - Sep 1 2006

Funding

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.

ASJC Scopus subject areas

General Medicine

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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Jacobson, J. M., Bucy, R. P., Spritzler, J., Saag, M. S., Eron, J. J., Coombs, R. W., Wang, R., Fox, L., Johnson, V. A., Cu-Uvin, S., Cohn, S. E., Mildvan, D., O'Neill, D., Janik, J., Purdue, L., O'Connor, D. K., Di Vita, C., & Frank, I. (2006). Evidence that intermittent structured treatment interruption, but not immunization with ALVAC-HIV vCP1452, promotes host control of HIV replication: The results of AIDS Clinical Trials Group 5068. Journal of Infectious Diseases, 194(5), 623-632. https://doi.org/10.1086/506364

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title = "Evidence that intermittent structured treatment interruption, but not immunization with ALVAC-HIV vCP1452, promotes host control of HIV replication: The results of AIDS Clinical Trials Group 5068",

abstract = "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.",

author = "Jacobson, {Jeffrey M.} and Bucy, {R. Pat} and John Spritzler and Saag, {Michael S.} and Eron, {Joseph J.} and Coombs, {Robert W.} and Rui Wang and Lawrence Fox and Johnson, {Victoria A.} and Susan Cu-Uvin and Cohn, {Susan E.} and Donna Mildvan and Dorothy O'Neill and Jennifer Janik and Lynette Purdue and O'Connor, {Deborah K.} and {Di Vita}, Christine and Ian Frank",

note = "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.{\textquoteright}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.",

year = "2006",

month = sep,

day = "1",

doi = "10.1086/506364",

language = "English (US)",

volume = "194",

pages = "623--632",

journal = "Journal of Infectious Diseases",

issn = "0022-1899",

publisher = "Oxford University Press",

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Jacobson, JM, Bucy, RP, Spritzler, J, Saag, MS, Eron, JJ, Coombs, RW, Wang, R, Fox, L, Johnson, VA, Cu-Uvin, S, Cohn, SE, Mildvan, D, O'Neill, D, Janik, J, Purdue, L, O'Connor, DK, Di Vita, C & Frank, I 2006, 'Evidence that intermittent structured treatment interruption, but not immunization with ALVAC-HIV vCP1452, promotes host control of HIV replication: The results of AIDS Clinical Trials Group 5068', Journal of Infectious Diseases, vol. 194, no. 5, pp. 623-632. https://doi.org/10.1086/506364

Evidence that intermittent structured treatment interruption, but not immunization with ALVAC-HIV vCP1452, promotes host control of HIV replication: The results of AIDS Clinical Trials Group 5068. / Jacobson, Jeffrey M.; Bucy, R. Pat; Spritzler, John et al.
In: Journal of Infectious Diseases, Vol. 194, No. 5, 01.09.2006, p. 623-632.

Research output: Contribution to journal › Article › peer-review

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.

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ER -

Evidence that intermittent structured treatment interruption, but not immunization with ALVAC-HIV vCP1452, promotes host control of HIV replication: The results of AIDS Clinical Trials Group 5068

Abstract

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