Improving HIV-specific immune responses in HIV-infected patients.

Deficiencies in potentially highly protective HIV-1-specific immune responses have led to interventions with immunotherapeutic strategies such as post-exposure vaccination. The application of exogenous antigen to the HIV-infected individual by therapeutic vaccination might be expected to induce renewed virus-specific effector T-cell and neutralising-antibody responses. However, the nature of HIV-1 immunopathogenicity precludes this approach: high levels of viral turnover, persistent expression and presentation of HIV-1 antigen to the immune system, T-cell hyperactivation and exhaustion and clonal T-cell anergy all successfully counter any effect of exogenous antigen. Even with the use of highly active antiretroviral therapy (HAART), when HIV-1 activity is profoundly restricted, the induction of immune responses remains problematic. Different vaccine strategies are currently being tested, including a whole killed virus preparation (Remune), a yeast virus-like particle (p24 VLP), whole antigen preparations (VaxSyn), canarypox immunogens (ALVAC) and DNA plasmids. Therapeutic vaccine strategies currently in the earliest stages of development include adenovirus vectors and a topical DNA preparation, DermaVir.