Human immunodeficiency viruses and the acquired immunodeficiency syndrome

29. Human immunodeficiency viruses and the acquired immunodeficiency syndrome




Questions


image What are the basic features of the HIV virion?

image What are the principles of diagnosis of HIV infection?

image How are HIV infection and AIDS managed?

AIDS is the commonest cause of death in young adults in many parts of the world. The major burden of infection is in Africa, Southeast Asia, India and South America, where heterosexual transmission predominates and the number of cases in men and women are approximately equal. In Europe and North America, homosexual transmission has been responsible for the majority of cases. Apart from transmission by sexual contact, transfer has also occurred by blood and blood products, including injectable drug use, and vertically from mother to child.



The viruses


There are two viruses, HIV-1 and HIV-2, which are accepted causes of AIDS. Structurally, these viruses are identical (Fig. 3.29.1). They are retroviruses, so-called because they encode an enzyme, reverse transcriptase, that makes a DNA copy of genomic RNA when it infects cells; this is ‘backwards’ (Greek retro) to the classic RNA from DNA. The replication cycle of HIV-1 is shown in Fig. 3.29.2. Other retroviruses that are known to infect humans are human T cell lymphotropic viruses (HTLV) 1 and 2, but they are associated with lymphoma and neurological disease not AIDS.


image

Fig. 3.29.1 Structure of the human immunodeficiency virus.


image

Fig. 3.29.2 Replication cycle of human retroviruses.


HIV undergoes rapid evolution, with quasispecies being produced as reverse transcriptase makes mistakes in copying the original genome. These are grouped as strains or clades, with HIV-1B being the virus that was first recognized in the USA.



HIV disease and pathogenesis


HIV infects T lymphocytes and macrophages. These cells express CD4 (and other cell surface molecules, such as CCR5), which the virus uses to attach to the cell. Early infection takes place predominantly in the lymph nodes, although CD4-positive cells in tissues such as the brain and gut are also infected. This initial infection elicits a vigorous immune response, which is detectable as anti-HIV antibody after 4–8 weeks. In many cases, this primary illness (or ‘seroconversion illness’) is manifest as a glandular fever-like illness 2–12 weeks after initial infection. Uncommonly, infection is aborted at this stage, but in the majority there follows a long incubation period with continued viral replication (over 10 billion new viruses per day) accompanied by a large turnover of immune cells. This period lasts months or years, with increasing lymph node activity, which can be eventually detected clinically as a persistent generalized lymphadenopathy. As the destruction of immune cells becomes greater than new immune cell production, AIDS develops.


AIDS is symptomatic HIV infection. It is a clinical diagnosis based on the presence of a number of ‘AIDS-defining illnesses’, usually with detectable anti-HIV antibody. These illnesses are, with few exceptions, ‘opportunistic’ infections and tumours. There are several international definitions of AIDS, but the most common examples of infections and tumours are:


image infections
– Candida (oral, oesophageal, tracheal, lung)
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Jul 3, 2016 | Posted by in MUSCULOSKELETAL MEDICINE | Comments Off on Human immunodeficiency viruses and the acquired immunodeficiency syndrome

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