HIV, the virus that causes AIDS, has claimed the lives of more than 21 million people, and about 36 million individuals are currently living with HIV. The incidence of new HIV infection is increasing at an alarming rate worldwide.

Antiviral drugs have been developed that slow the course of HIV infection, but it is clear that existing drug treatments are not adequate long-term solutions. Therapeutic regimens that achieve virological control without the use of massive amounts of drugs are sorely needed. New therapeutic strategies will need to be guided by a better understanding of the fundamental mechanisms by which HIV causes AIDS.

Perhaps most urgent is the need for a reliable, readily available vaccine against HIV. Historically, vaccines have been our most effective weapon for minimizing the consequences of viral infections. Smallpox, polio, measles, and yellow fever are prominent examples. We now realize, however, that development of an effective vaccine against HIV is a more formidable challenge than we have ever faced previously.

The main obstacle facing development of a vaccine against HIV is the persistent nature of viral replication. Although individuals infected with HIV can mount a strong immune response, the virus counters with a variety of evasion strategies and unrelenting replication. Vaccines must be designed to counteract these immune evasions in order to allow the immune response to be effective.

Researchers in the Divisions of Microbiology, Immunology, Comparative Pathology, and Primate Resources are working together with investigators from other institutions to develop a practical vaccine against HIV. These efforts focus on strategies to promote continuous antigen expression and persistent immune responses, and include live attenuated vaccine approaches, recombinant herpesviruses, and recombinant bacteria to colonize the gut.

Center scientists are also working to understand the fundamental mechanisms by which HIV and SIV, the nonhuman primate equivalent of HIV, cause AIDS. Ongoing programs are investigating the role of gut-associated lymphoid tissue and thymus in early stages of infection, the mechanisms responsible for viral-induced brain disease and dementia, the strategies by which HIV and SIV evade immune responses, the role of auxiliary genes in progression of HIV and SIV infection, and the mechanisms of immunological control in rare cases of viral infection that do not result in AIDS. Other novel therapeutic approaches, including gene therapy and regimens to promote immunological control in the absence of antiviral drugs, are also being actively pursued.