ObjectiveWe examined the activity of an HIV-1 immunogen (Remune) on viral load, CD4 cells and HIV-1 speci®c immunity.
MethodsPlasma and peripheral blood mononuclear cells were obtained in a prede®ned random subset of subjects (n = 252) from a multicentre, double-blind, adjuvant-controlled phase III clinical endpoint study.
ResultsThe subjects treated with the HIV-1 immunogen had a signi®cantly greater decline in viral load at multiple time points (P < 0.05), a trend towards increased CD4+ T cell counts and signi®cantly enhanced HIV-1 speci®c immune responses as measured by HIV-1 lymphocyte proliferation (P < 0.001) compared to the adjuvant control group. Furthermore, in the HIV-1 immunogen treated group, enhanced HIV-1 speci®c lymphocyte proliferative immune responses were associated with decreased HIV-1 plasma RNA.
ConclusionThese results suggest that, in a prede®ned, random subset of subjects, a bene®cial effect of the HIV-1 immunogen was observed on viral load, CD4+ T cells, and HIV-speci®c immunity. These differences were observed in a background of multiple drug therapies. Ongoing trials are evaluating the effect of the combination of this HIV-1 speci®c, immune-based therapy with potent antiviral drug therapy on virological outcomes.
IntroductionRecent advances in HIV-1 antiviral drug therapy have had a signi®cant impact on AIDS morbidity and mortality in industrialized countries [1±3]. In North America and Europe antiviral drug`cocktails' (antiretroviral therapy), which include a protease inhibitor (PI), have become the standard of care [4]. Nevertheless, reservoirs of replication competent HIV-1 appear to be maintained despite chronic treatment with combination antiviral drug therapy [5,6]. This may, in part, explain some recent reports suggesting the occurrence of virologic failure in approximately 20± 40% of patients after 2 years of potent antiviral drug therapy [7,8] We examined the effect of HIV-1 speci®c, immunebased therapy in a large, multicentre, phase III, clinical endpoint study, which began in the spring of 1996, just prior to the approval of the newer more potent antiviral drug therapies such as PIs. With the anticipation that these newer agents would become part of the standard of care, subjects were allowed to take any combination of antiviral drug therapy and to switch combinations without restrictions during this trial. Asymptomatic HIV-1 infected subjects with CD4 cell counts of 300±549 cells/mL were randomized to receive the HIV-1 immunogen (Remune) or the adjuvant control (incomplete Freund's adjuvant; IFA) and followed for an average of 2.5 years with the primary endpoint being time to clinical progression or death. The trial was halted by an independent data safety monitoring board (DSMB) due to lack of signi®cant differences between the two treatment groups in terms of clinical endpoints, although signi®cant effects were observed on CD4+ T cell counts favouring the HIV-1 immunogen group (P < 0.05), as reported elsewhere [23]. Within this trial, a randomly selected, prede®ned subset...