Early Events in HIV Infection

Once it enters the body, HIV infects a large number of CD4+ cells and replicates rapidly. During this acute or primary phase of infection, the blood contains many viral particles that spread throughout the body, seeding various organs, particularly the lymphoid organs .

Two to 4 weeks after exposure to the virus, up to 70 percent of HIV-infected people suffer flu-like symptoms related to the acute infection.  Their immune system fights back with killer T cells (CD8+ T cells) and B-cell-produced antibodies, which dramatically reduce HIV levels.  A person’s CD4+ T cell count may rebound somewhat and even approach its original level.  A person may then remain free of HIV-related symptoms for years despite continuous replication of HIV in the lymphoid organs that had been seeded during the acute phase of infection.

One reason that HIV is unique is the fact that despite the body’s aggressive immune responses, which are sufficient to clear most viral infections, some HIV invariably escapes. This is due in large part to the high rate of mutations that occur during the process of HIV replication.  Even when the virus does not avoid the immune system by mutating, the body’s best soldiers in the fight against HIV may be depleted or become dysfunctional.  In addition, early in the course of HIV infection, people may lose HIV-specific CD4+ T cell responses that normally slow the replication of viruses.  Such responses include the secretion of interferons and other antiviral factors, and the orchestration of CD8+ T cells.

Finally, the virus may hide within the chromosomes of an infected cell and be shielded from surveillance by the immune system.  Such cells can be considered as a latent reservoir of the virus.  Because the antiviral agents currently in our therapeutic arsenal attack actively replicating virus, they are not effective against hidden, inactive viral DNA (so-called provirus). New strategies to purge this latent reservoir of HIV have become one of the major goals for current research efforts.

Epidemiologic studies in Western countries have shown that the median time from infection with HIV to the development of AIDS-related symptoms has been approximately 10 to 12 years in the absence of antiretroviral therapy.  There is, however, a wide variation in disease progression.  Approximately 10 percent of HIV-infected people in these studies have progressed to AIDS within the first 2 to 3 years following infection, while up to 5 percent of individuals in the studies have stable CD4+ T cell counts and no symptoms even after 12 or more years.  Factors such as age or genetic differences among individuals, the level of virulence of an individual strain of virus, and co-infection with other microbes may influence the rate and severity of disease progression.  Drugs that fight the infections associated with AIDS have improved and prolonged the lives of HIV-infected people by preventing or treating conditions such as Pneumocystis carinii pneumonia, cytomegalovirus disease, and diseases caused by a number of fungi.

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