Inactivated HIV-1 Immunogen

Impact on Markers of Disease Progression

Abstract

The pursuit of valid markers of disease progression in human immunodeficiency virus type 1 (HIV-1) infection is especially relevant considering the potential treatment alternatives that presently are under evaluation. Because HIV-1 infection results in a virally induced immune suppression characterized by the loss of cell-mediated immunity (CMI), depletion of CD4⁺ cells, loss of core antibody, and an increase in viral burden, these markers seemed to be appropriate to monitor in a controlled study. We monitored a number of virologic, immunologic, and cytologic markers of disease progression in 103 subjects who were enrolled in a 12-month, double-blind, randomized, adjuvant-controlled study of the HIV-1 inactivated Immunogen. The markers included HIV-1 DNA, HIV-1 RNA, CD4 percent, p24 antibody, and lymphocyte proliferation. Analysis of HIV-1 DNA with a quantitative poly-merase chain reaction (PCR) assay indicated a treatment effect on viral burden in the HIV-1 Immunogen-treated group. Analysis of HIV-1 RNA revealed a similar trend favoring the Immunogen-treated group. In addition, a significant effect was shown on CD4 percent and CMI in the Immunogen-treated group. An analysis of CMI that used stimulation indices underrepresented the immunogenicity of the Immunogen. Further examination revealed that the lymphocytes of the HIV-1 Immunogen-treated patients were proliferating in vitro without exogenous antigen. Although the clinical significance of this phenomenon currently is unknown, it may be a relevant prognostic marker for assessment of HIV-1 therapy. The data presented here support the concept that immunotherapy with the HIV-1 Immunogen may slow disease progression. Future studies will evaluate whether the concordant treatment effects observed on markers of disease progression in this study translate into clinical benefit.