Impact of therapeutic immunization on HIV-1 viremia after discontinuation of antiretroviral therapy initiated during acute infection.
Treatment strategies that would induce durable virological control of human immunodeficiency virus (HIV)-1 in the absence of continued antiretroviral therapy (ART) are highly desirable.METHODS. We assessed, in a randomized, double-blind, placebo-controlled trial, whether the addition of therapeutic vaccines (ALVAC-HIV [vCP1452] or ALVAC-HIV and Remune) to ART initiated during acute infection could increase the probability of having a plasma viral load </=1000 HIV-1 RNA copies/mL 24 weeks after planned discontinuation of ART.RESULTS. All 79 randomized subjects completed the immunization schedule, and 78 discontinued ART with no major safety concerns. After immunization, subjects in the vaccine study arms had significantly increased HIV-1-specific CD4(+) and CD8(+) T cell responses, by interferon- gamma enzyme-linked immunospot assay, compared with those in the placebo study arm. Overall, 17.7% of subjects had </=1000 HIV-1 RNA copies/mL 24 weeks after discontinuation of ART, with no significant difference between the vaccine study arms and the placebo study arm (15.4% vs. 22.2%; difference, -6.8% [95% confidence interval, -26.8% to 10.0%]; P=.54).CONCLUSION. Therapeutic immunization and ART, compared with ART alone, generated HIV-1-specific cellular immunity but did not lead to better virological control of HIV-1 24 weeks after discontinuation of ART. Our trial design appears to be feasible and safe for testing future immune-boosting strategies.
Kinloch-de Loes
Sabine
S
Department of Medicine, Royal Free Centre for HIV Medicine, Royal Free and University College Medical School, London, United Kingdom. sabine@kinloch.u-net.com
Hoen
Bruno
B
Smith
Don E
DE
Autran
Brigitte
B
Lampe
Fiona C
FC
Phillips
Andrew N
AN
Goh
Li-Ean
LE
Andersson
Jan
J
Tsoukas
Christos
C
Sonnerborg
Anders
A
Tambussi
Giuseppe
G
Girard
Pierre-Marie
PM
Bloch
Mark
M
Battegay
Manuel
M
Carter
Nick
N
El Habib
Raphaelle
R
Theofan
Georgia
G
Cooper
David A
DA
Perrin
Luc
L
D016915:AIDS Vaccines / Q000627:therapeutic use*; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage*; D004311:Double-Blind Method; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000628:therapy*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood; D019562:Viral Load; D014766:Viremia / Q000188:drug therapy / Q000628:therapy*
D016915:AIDS Vaccines; D019380:Anti-HIV Agents; D012367:RNA, Viral