Augmentation of HIV-1-specific T helper cell responses in chronic HIV-1 infection by therapeutic immunization.
OBJECTIVE
To determine whether therapeutic immunization with a whole inactivated HIV-1 immunogen augments HIV-1-specific T helper cell responses in chronically infected individuals receiving suppressive antiretroviral therapy (ART).


METHODS
An investigator-initiated, single center, double-blind, placebo-controlled, randomized trial.


METHODS
Subjects selected for study were HIV-1-infected adults on ART with an HIV-1-RNA plasma viral load of less than 500 copies/ml for at least 6 months, and a CD4 cell count greater than 250 cells/mm3 before starting ART. Study subjects were randomly assigned to receive either immunogen (inactivated envelope-depleted HIV-1 coupled with incomplete Freund's adjuvant; IFA), versus placebo (IFA alone). The primary outcome was significant CD4 cell lymphoproliferative responses to HIV-1 proteins. Secondary endpoints included HIV-1-specific CD8 T cell responses, CD4 cell count/percentage, HIV-1-RNA plasma viral load, and delayed-type hypersensitivity (DTH) responses.


RESULTS
The augmentation of HIV-1-specific T helper cell responses was achieved in five out of five vaccine recipients and none out of four controls (P = 0.008, Fisher's exact test). There were no significant changes in the breadth or magnitude of cytotoxic T lymphocyte responses, CD4 cell count/percentages, or DTH test responses.


CONCLUSIONS
HIV-1-specific T helper cell responses can be successfully increased by therapeutic immunization in individuals with chronic infection on suppressive ART. Further studies will be needed to determine whether the augmentation of these responses correlate with long-term clinical benefits.
Robbins
Gregory K
GK
Partners AIDS Research Center and Infectious Disease Division, Massachusetts General Hospital, Division of AIDS Harvard Medical School, Boston, 02114, USA.
Addo
Marylyn M
MM
Troung
Hien
H
Rathod
Almas
A
Habeeb
Kathy
K
Davis
Benjamin
B
Heller
Howard
H
Basgoz
Nesli
N
Walker
Bruce D
BD
Rosenberg
Eric S
ES
D016915:AIDS Vaccines / Q000627:therapeutic use*; D000328:Adult; D018791:CD4 Lymphocyte Count; D002908:Chronic Disease; D003602:Cytotoxicity, Immunologic; D004311:Double-Blind Method; D005260:Female; D015658:HIV Infections / Q000276:immunology / Q000628:therapy*; D015497:HIV-1; D006801:Humans; D007114:Immunization; D008297:Male; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
D016915:AIDS Vaccines; C105086:remune