Not all exposure to HIV, be it through unprotected sex or sharing of needles, results in infection. Whether infection occurs seems to depend on factors such as amount of inoculum, pathogenicity of virus, and host resistance. In terms of sexual transmission, the presence of sores, other venereal disease, and mucosal tears may all facilitate transmission.
Once HIV gains access to a tissue, its replication depends on its ability to enter host cells. Such entry appears to require at least two types of receptors (docking mechanisms on cell surfaces). Sections of viral envelope protein (gp120) are capable of attaching to CD4 receptor sites on host cells. However, full attachment leading to fusion of virus with cell requires a coreceptor of the chemokine type. Dozens of types of chemokine receptors are known, but the most important in terms of HIV infection appear to be CXCR4 [found predominantly on CD4 (T4) lymphocytes] and CCR5 (found on macrophages, dendritic cells, and other cells).
Once virus successfully enters host cells, replication begins. The presence of viral RNA can be found in the blood of infected individuals within 1 week of infection. Initially, there is a rapid proliferation of virus, with as many as 10 billion virions being formed every day, accompanied by massive destruction of CD4
lymphocytes of which millions must be replaced on a daily basis. Within several weeks to months, however, a "steady state'' is reached wherein the host's defenses succeed in suppressing viral replication. At this point, viral load in the blood is significantly reduced or may even become undetectable. Antibody to HIV is present, however, and it is the basis for the commonly used HIV test (the enzyme-linked immunosorbent assay).
For reasons that are still incompletely understood, host responses are not ultimately effective in eradicating HIV. Chronically infected host cells (e.g., in lymph nodes) continuously seed HIV, which may gradually undergo further genetic variation (termed quasispecies formation) that may create genotypes that are increasingly more successful in eluding host defenses. Over the years, the host's capacity to mount an effective immune response diminishes, leading to a critical drop in CD4 lymphocyte concentration (normal CD4 counts are on the order of 1000 cells per cubic millimeter; persons with CD4 counts below 200 per cubic millimeter are diagnosed as having AIDS).
The collapse of cell-mediated immunity sets the stage for infection by organisms that are normally held in check by these mechanisms. These include various mycobacteria, fungi, yeasts, protozoa, as well as cancers stimulated by proliferation by other viruses (e.g., Kaposi sarcoma, which is linked to herpesvirus infection).
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