Acquired Immune Deficiency Syndrome

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Introduction

Acquired Immune Deficiency Syndrome (AIDS), a clinical syndrome (a group of various illnesses that together characterize a disease) resulting from damage to the immune system caused by infection with the human immunodeficiency virus (HIV).

In HIV-infected individuals, there is a gradual loss of immune cells (called CD4+ T-lymphocytes) and immune function. The mechanisms by which HIV causes this immune deficiency are still not completely understood, although direct infection of CD4+ T-lymphocytes by HIV certainly plays a role. The loss of immune function, if untreated, results eventually in the development of opportunistic diseases caused by common infections that do not present a threat to healthy individuals, including fungal, bacterial, protozoal, and viral diseases, as well as by malignancies that appear to be associated with immune dysregulation. In the absence of treatment, it generally takes six to ten years from the point of infection to develop AIDS, although the rate of disease progression may vary substantially from person to person.

In the early 1980s deaths by opportunistic infections, previously observed mainly in transplant recipients receiving immunosuppressive therapy, were recognized in otherwise healthy homosexual men. In 1983, Luc Montagnier and scientists at the Pasteur Institute in Paris isolated what appeared to be a new human retrovirus from the lymph node of a man at risk of developing AIDS. Almost simultaneously, both Robert Gallo’s group at the National Cancer Institute (NCI), and a group headed by Jay Levy at the University of California, San Francisco, isolated a retrovirus from AIDS patients and from people who had had sexual contact with AIDS patients. All three groups had isolated what is now known as HIV—the aetiological (causative) agent of AIDS.

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Detection and Diagnosis

With the identification of HIV in 1983 came the opportunity to develop a method of specific detection. The screening tests now in widespread use by blood banks, plasma centres, reference laboratories, private clinics, and health departments analyse a sample of blood for the presence of antibodies produced by the immune system in response to infection with HIV. Separate serological tests were developed to detect HIV-1 and HIV-2, owing to the major differences in the protein components of these two related viruses. There are also different sub-types (or 'clades') of HIV-1 and HIV-2, reflecting the different evolutionary paths that the viruses have taken in specific geographical locations. As new sub-types of HIV are identified from around the world, they too will need to be evaluated for detection by these tests.

There is a brief “window period” (normally four to eight weeks) after exposure to HIV during which standard screening tests are unable to detect the presence of HIV because the immune system has not had enough time to make antibodies against HIV. During this period, other methods that use amplification techniques (such as polymerase chain reaction) to detect the genetic material of the virus itself, rather than antibodies against it, may be able to determine whether an individual is infected with HIV.

A person who receives a positive test result for HIV infection is often described as HIV-positive. Being HIV-positive does not necessarily imply that a person also has AIDS. A person can be infected with HIV for a long period—greater than ten years—without developing any of the clinical illnesses that constitute a diagnosis of AIDS.

The Centers for Disease Control and Prevention in Atlanta, Georgia, established an authoritative definition for the diagnosis of AIDS: in an HIV-positive individual, the CD4+ cell count must be below 200 cells per cu mm of blood, or there must be the clinical appearance of a specific opportunistic condition that is considered AIDS-defining, from a long list that includes Pneumocystis carinii pneumonia (PCP), oesophageal candidiasis (thrush), pulmonary tuberculosis, and invasive cervical carcinoma. In Europe, however, a CD4+ cell count below 200 is not in itself grounds for the diagnosis of AIDS; HIV-positive people must have an AIDS-defining opportunistic illness to be diagnosed with AIDS.

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Nature of the Disease

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Clinical Progression of AIDS

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Measuring Progression

The progression from the point of HIV infection to the occurrence of one (or more) of the clinical diseases that define AIDS may take six to ten years or longer. The progression to disease in HIV-infected individuals can be monitored using surrogate markers (laboratory data that correlate with disease progression), or clinical end points (illnesses that can occur after a specific degree of immunosuppression has been reached). Surrogate markers for the various stages of HIV disease include the progressive loss of CD4+ T-lymphocytes (CD4+ T-cells), the major white blood cells lost through HIV infection. In general, the lower the patient's CD4+ T-cell count, the more advanced is the degree of immunosuppression. The amount of HIV circulating in the blood is a second surrogate marker. Using sensitive detection techniques, the quantity of HIV in the blood of an untreated individual correlates with the clinical stage of the disease and predicts the rate of disease progression.

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Acute Retroviral Syndrome

A well-recognized progression of disease occurs in untreated HIV-infected individuals. Within one to three weeks after infection with HIV, many (but not all) individuals experience non-specific flu-like symptoms that may include fever, headache, skin rash, tender lymph nodes, and malaise, lasting approximately one to two weeks. During this phase, termed acute retroviral syndrome or primary HIV infection, HIV reproduces itself to very high levels, circulates through the blood, and establishes infections in tissues throughout the body, especially in the lymph nodes. Patients’ CD4+ cell counts fall briefly but return to near-normal levels as the immune system recognizes the infection and mounts an immune response that reduces HIV replication, albeit incompletely.