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).

Design:

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/mm 3 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.

Conclusion:

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.