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.
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 interruption (ATI).


METHODS
Ninety-seven subjects receiving stable ART with an HIV-1 RNA load <50 copies/mL and CD4(+) T lymphocyte count >400 cells/mm(3) 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 <1,000 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.
Jacobson
Jeffrey M
JM
Beth Israel Medical Center and Albert Einstein College of Medicine, New York, NY 10003, USA. jjacobson@chpnet.org
Pat Bucy
R
R
Spritzler
John
J
Saag
Michael S
MS
Eron
Joseph J
JJ
Coombs
Robert W
RW
Wang
Rui
R
Fox
Lawrence
L
Johnson
Victoria A
VA
Cu-Uvin
Susan
S
Cohn
Susan E
SE
Mildvan
Donna
D
O'Neill
Dorothy
D
Janik
Jennifer
J
Purdue
Lynette
L
O'Connor
Deborah K
DK
Vita
Christine Di
CD
Frank
Ian
I
D016915:AIDS Vaccines / Q000008:administration & dosage / Q000627:therapeutic use*; D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy / Q000276:immunology*; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage; D002986:Clinical Trials as Topic; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006678:HIV / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D044469:Racial Groups; D012008:Recurrence; D019562:Viral Load; D014765:Viral Vaccines / Q000008:administration & dosage / Q000627:therapeutic use*; D014779:Virus Replication / Q000187:drug effects*
D016915:AIDS Vaccines; C078788:ALVAC vaccine; D019380:Anti-HIV Agents; D014765:Viral Vaccines