Development of immunotherapeutic strategies for HIV-1

In the majority of untreated patients, HIV-1 infection presents as a progre ssive disease of the immune system. Recent studies indicate that immune res ponses can be induced in HIV-1 infected individuals, leading to some immune control of virus replication. Such immune responses are also observed in s mall numbers of untreated HIV-1 infected long-term non-progressor (LTNP) pa tients, as well as in other viral infections (including those with human he rpesviruses). Emerging novel technologies, animal studies and detailed immu nological studies have proven invaluable in defining the immune responses t hat are associated with a favourable clinical outcome. Central effector and regulatory cells are HIV-1-specific CD8+ cytotoxic T-lymphocytes (CTL) and CD4+ helper T-lymphocytes respectively. Fully functional antigen-presentin g cells (APC) are also essential in all stages of HIV-1 infection and possi bly some (but not all) antibody responses contribute to beneficial drug the rapy, immunity. The availability of combination anti-retroviral which succe ssfully controls viraemia, has enabled a beneficial outcome in HIV-1 infect ed individuals. Since no chronically HIV-1 infected patient many has been s hown to eradicate virus, novel approaches utilising therapeutic immunisatio n and various cytokines to manipulate immune responses and to induce and st eer immunity towards a desired phenotype are required. There is a clear rat ionale for immunotherapeutic intervention in chronic progressive HIV-1 infe ction, which forms the foundation for novel approaches aimed at inducing an d maintaining immune control. Here we review the immuneopathogenesis of HIV -1 infection and discuss the promises of therapeutic immunisation and immun otherapy in general and their potential in the treatment of chronic HIV-1 d isease.