Factors affecting the natural history of human immunodeficiency virus infection.

Abstract

Human immunodeficiency virus (HIV) establishes latent infection in CD4 lymphocytes and macrophages. It can destroy CD4 cells by direct virus cytotoxicity, indirectly through the host response against HIV-infected cells, or by both means. Cells of the macrophage lineage are generally not destroyed but can serve as a reservoir of virus. HIV also causes functional impairment in remaining infected and uninfected cells. After exposure to infection by sexual, blood or maternofetal contact, about half the contacts become infected with HIV. Factors influencing the inoculum derived from the infected person include type of contact, phase of infection and local factors enhancing HIV replication or excretion. In the exposed person, genetic factors and systemic or local events such as infection or inflammatory injury may influence relative susceptibility. After infection with HIV, a number of outcomes may be seen, including symptomless carriage, with or without lymphadenopathy, or symptomatic disease, including the AIDS-related complex, acquired immune deficiency syndrome and HIV encephalopathy. Infection, multiple pregnancy and infancy are associated with increased or more rapid progression to symptomatic disease; malnutrition and immunosuppressive drugs may exert a similar effect. Genetic factors appear to affect disease susceptibility. Mechanisms influencing progression can be divided into those affecting the rate of HIV replication, those that determine the host response to HIV, and those mediated by other immunosuppressive influences. The host's balance with HIV thus resembles that of a tightrope walker, any force tending to tip him towards a catastrophic and irretrievable decline.