Pathogenesis and Clinical Manifestations of HIV-1 Infection

Abstract

HIV-1 is a member of the lentivirus family of human retroviruses. As such, it shares several biologic and molecular properties with a number of related agents affecting nonhuman primates, goats, sheep, and horses. In addition to HIV-1, a related human pathogen, HIV-2, has also been identified. This agent has also been associated with AIDS in humans, but most current information suggests that HIV-2 is less pathogenic than HIV-1. These agents are enveloped viruses that carry their genetic information in the form of two identical strands of RNA that must be reverse transcribed to DNA following infection of mammalian cells. This process is the basis for the nomenclature of the retrovirus family. Following reverse transcription, the double-stranded DNA product may remain within the cytoplasm, or it may be transported to the nucleus where it integrates within the genome of the host cell and establishes lifelong infection of that cell and its progeny. Although the complement of regulatory genes varies somewhat from one retrovirus to another, these agents share the property of having a complex set of genes that regulate viral expression within the host cell, and that are clearly integral components of the pathogenesis of retroviral infection. Clinical manifestations of infection, likewise, are host and virus dependent, and include both direct manifestations of the viral infection and indirect effects mediated through effects of the viruses on specific organ systems. In the case of HIV-1, the major target organs are the immune and central nervous systems. In addition, in late stages of the disease process an increasing array of metabolic disturbances are encountered that contribute to the wasting syndrome frequently observed in advanced HIV-1 infection. This chapter will focus primarily on clinical manifestations of HIV-1 infection that are directly attributable to HIV-1 infection.