Etiology and Epidemiology

The first cases of acquired immunodeficiency syndrome (AIDS) in the United States were reported in 1981.2 Soon thereafter, the HIV, which is an RNA virus of the Retroviridae family, was identified as the underlying pathogen. The HIV probably entered the human population by cross-species transmission of the ancestral virus found in wild chimpanzees in Central Africa. The spread of the HIV in Africa corresponds to urbanization and occurred before the recognition of AIDS.3

The HIV is a bloodborne pathogen acquired in non-occupational settings most readily either across mucous membranes or parenterally by 5 prime modes of transmission:

  1. unprotected penetrative sex between men,
  2. unprotected heterosexual intercourse,
  3. injection drug use,
  4. unsafe blood and blood by-products (primarily in developing countries), and
  5. mother to child spread during pregnancy, delivery, or breast feeding.4

The estimated per exposure risk of HIV transmission following (1) receptive anal intercourse is 1 to 30%; (2) insertive anal or receptive vaginal intercourse it is 0.1 to 10%; (3) insertive vaginal intercourse it is 0.1 to 1%; and (4) injection drug use with needle sharing it is 0.67 per needle-sharing contact.5 The risk increases with advanced HIV disease, cervical or anal dysplasia, circumcision status, and the presence of genital ulcer disease. Data are lacking on transmission of HIV via oral sex.

Image: Diagram of Helper T Cell

The HIV has the same general life cycle as other viruses. Infection begins when a virion attaches to a host cell. CCR5 and CXCR4 are the two major co-receptors used by HIV-1. The viral strains can be classified on the basis of which co-receptor they use as CCR5-tropic, CXCR4-tropic, or mixed-tropic. CCR5-tropic strains predominate during early stages of infection and remain dominant in 50-60% of late stage disease.6 Capsid- or envelop-related viral proteins mediate attachment.

Viral entry into the host cell is mediated by other viral proteins which promote the fusion of the viral capsid or envelop with host cell membrane. Once the virus has gained entry into the host cell, it loses its capsid proteins by the process known as uncoating. The viral nucleic acid now becomes available for replication, which requires the generation of protein kinase-dependent nucleoside triphosphates (ribo- or deoxyribo-) to be incorporated into the new viral genome by viral or host cell polymerases.

In most instances the viral DNA or RNA is replicated and then transcribed into a mRNA. Since the HIV is an RNA retrovirus, uncoating is followed by reverse transcription, i.e., the viral RNA is first copied into DNA and then it is transcribed into a mRNA. Next, the newly synthesized mRNA is translocated to host cell ribosomes. Viral proteins synthesized by host cell ribosomes are then assembled with the duplicate viral genome. Assembly is followed by the process of maturation.

Maturation, characterized by cleavage of viral proteins by proteases, is essential for the newly formed virion to become infectious. Following maturation viruses egress from the host cell either by cell lysis or budding through the cell membrane. Replication of the HIV may include the additional step of integration, i.e., the viral genome may be incorporated into the host genome. The process of integration is responsible for the capacity of certain viruses, i.e., oncogenic viruses, to induce tumor growth.