Can the immune response control HIV infection?

Human immunodeficiency virus (HIV) constitutes an unprecedented challenge to medical science. Once an HIV infection is established, its clinical course, while protracted , is generally inexorable. With the possible exception of a group of recently described "long-term nonpro-gressors," virtually all HIV-infected individuals eventually develop acquired immunodeficiency syndrome (AIDS), the outcome of which is almost invariably fatal. The course of HIV infection is quite different from that encountered in the great majority of infectious diseases. The more normal experience in the contest between pathogens and their hosts is that of an acute infection in which some fraction of those infected recover and, thereafter , express solid immunity, protecting them against the same or related agents. Generally, the nature of protective immunity expressed by those that have recovered from infection may be used as a guide to the type of response that a vaccine should induce to provide protection. In the case of HIV, it has generally been believed that infected individuals never purge themselves of the virus, although this now appears to have been an oversimplification. The lack of information that would usually be provided by study of those who had recovered has meant that no correlation between type of immunity and protection could be drawn to guide scientists in their efforts to develop protective anti-HIV vaccines. A Vigorous Immune Response Occurs in Response to HIV Infection Does an effective immune response occur in infected indi-viduals? Perhaps surprisingly, in view of the apparent inev-itability of progression, the weight of evidence strongly suggests that a highly effective immune response does occur and that it contains the virus for a long period of time, although it rarely eradicates it. Infected individuals produce large amounts of anti-HIV antibody, the appearance of which has become the hallmark for the diagnosis of infection. Neutralizing antibody is commonly observed, although it is generally not detectable until after the initially high viral titers have fallen to the low levels that characterize the period of clinical latency (Robert et al., 1988; Saw-yer et al., 1990). Indeed, development of neutralizing anti-body that is cross-reactive on HIV strains other than that causing the infection may be even more protracted. The role of such neutralizing antibody in the control of HIV in the infected individual is not truly understood. Indeed, we do not yet know whether the small subset of infected individuals who become long-term nonprogressors may show earlier and more vigorous …