INACTIVATED HIV-1 IMMUNOGEN - IMPACT ON MARKERS OF DISEASE PROGRESSION

The pursuit of valid markers of disease progression in human immunodef iciency virus type 1 (HIV-1) infection is especially relevant consider ing the potential treatment alternatives that presently are under eval uation. Because HIV-1 infection results in a virally induced immune su ppression characterized by the loss of cell-mediated immunity (CMI), d epletion of CD4(+) cells, loss of core antibody, and an increase in vi ral burden, these markers seemed to be appropriate to monitor in a con trolled study. We monitored a number of virologic, immunologic, and cy tologic markers of disease progression in 103 subjects who were enroll ed in a 12-month, double-blind, randomized, adjuvant-controlled study of the HIV-1 inactivated Immunogen. The markers included HIV-1 DNA, HI V-1 RNA, CD4 percent, p24 antibody, and lymphocyte proliferation. Anal ysis of HIV-1 DNA with a quantitative polymerase chain reaction (PCR) assay indicated a treatment effect on viral burden in the HIV-I Immuno gen-treated group. Analysis of HIV-1 RNA revealed a similar trend favo ring the Immunogen-treated group. In addition, a significant effect wa s shown on CD4 percent and CMI in the Immunogen-treated group. An anal ysis of CMI that used stimulation indices underrepresented the immunog enicity of the Immunogen. Further examination revealed that the lympho cytes of the HIV-1 Immunogen-treated patients were proliferating in vi tro without exogenous antigen. Although the clinical significance of t his phenomenon currently is unknown, it may be a relevant prognostic m arker for assessment of HIV-1 therapy. The data presented here support the concept that immunotherapy with the HIV-1 Immunogen may slow dise ase progression. Future studies will evaluate whether the concordant t reatment effects observed on markers of disease progression in this st udy translate into clinical benefit. Key Words: