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1| Natural History and Classification

Stages

The natural history of untreated HIV infection is divided into the following stages:

Viral transmission Acute retroviral syndrome Recovery + seroconversion Asymptomatic chronic HIV infection Symptomatic HIV infection/AIDS Death
s

 FIGURE 1-1: Natural history of HIV infection in an average patient without antiretroviral therapy from the time of HIV transmission to death at 10-11 years.

Life cycle and natural history of HIV: The external glycoprotein gp 120 attaches to the CD4 cell receptor. This is followed by insertion of gp41 in to the CD4 cell, resulting in membrane fusion and fusion within pores followed by release of viral core into the CD4 cell cytoplasm (Lancet 2006; 368:489). The HIV genome is then reverse transcribed to DNA by reverse transcriptase. Viral DNA is then carried into the nucleus and inserted into host DNA by the viral integrase enzyme. Finally, translated viral proteins are processed by viral proteases, allowing assembly of new virions, which are released from the cell to infect other targets, completing the viral life cycle.

Immediately after infection, the virus is harbored in the gut-associated lymphoid tissue (GALT), the lymphatic tissue of the small bowel. The early phase of infection is characterized by viral amplification in GALT and peak viremia (106 – 107 c/ml) that is often associated with symptoms of the "acute retroviral syndrome" and massive depletion of activated and memory cells primarly from GALT (J Exp Med 2004; 200:761). The preferential depletion of CD4 cells from GALT persists despite antiretroviral therapy that often produces normal CD4 counts in peripheral blood. HIV replication persists throughout the disease despite absence of symptoms for years during most

 

2009 © John G. Bartlett, M.D. All rights reserved.1
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Chapter 1: Natural History and Classification

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