The main problem is the nature of the infection itself, featuring a virus that directly undermines the central component of adaptive immunity—the CD4 T cell—and that proliferates and mutates extremely rapidly to cause sustained infection in the face of strong cytotoxic Tcell and antibody responses. The development of vaccines that could be administered to patients already infected, to boost immune responses and prevent progression to AIDS, has been considered, as have prophylactic vaccines that would prevent initial infection. The development of therapeutic vaccination in those already infected would be extremely difficult. As discussed in the previous section, HIV evolves in individual patients by the selective proliferation of mutant viruses that escape recognition by antibodies and cytotoxic T cells. The ability of the virus to persist in latent form as a transcriptionally silent provirus invisible to the immune system might also prevent even an immunized person from clearing an infection once it has been established.
There has been more hope for prophylactic vaccination to prevent new infection. But even here, the lack of protection of the normal immune response and the sheer scale of sequence diversity among HIV strains in the infected population—there are currently thousands of different HIV strains circulating in the human population—remain significant challenges. Patients infected with one strain of virus do not seem to be resistant to closely related strains, and cases of superinfection, where two strains simultaneously infect the same cell, have also been described. This is compounded by the intrinsic difficulty in generating broadly neutralizing antibodies against HIV envelope glycoproteins (see Section 1331). Further, there remains uncertainty over what form protective immunity to HIV might take. It is now felt that induction of both effective antibody and Tcell responses will be required to achieve protective immunity, although which epitopes might provide the best targets and how best to induce them remain undefined. Finally, the time from conception to design to performance of complete clinical trials of vaccines against HIV takes years, slowing the rate of progress; to date, few major clinical vaccine trials have been completed, and those have failed.