Fundamental challenges to the development of a preventive HIV vaccine.

There is consensus that only a preventive vaccine can contain the HIV/AIDS pandemic. After 30 years still there is no preventive HIV vaccine. This article examines fundamental challenges to the development of a preventive HIV vaccine. They include the initially erroneous but powerful perception of the natural history of HIV disease, as an acute rather than a chronic illness even in the absence of therapy, the lack of appreciation of the quasispecies biology of HIV and the abandonment of principles of immunology theory caused by the allure of technological prowess. In addition two other important aspects are discussed: vaccines directed against transmitted/founder viruses (T/F) and the reconsideration of HIV inactivation as a viable means to obtain a preventive HIV vaccine using novel safe methods of inactivation not available during the early years of the pandemic.