Acquired Immunodeficiency Syndrome

Currently one of the most widely publicized diseases, acquired immunodeficiency syndrome (AIDS) is marked by progressive failure of the immune system. Although it's characterized by gradual destruction of cell-mediated (T-cell) immunity, it also affects humoral immunity and even autoimmunity because of the central role of the CD4 + T lymphocyte in immune reactions. The resultant immunodeficiency makes the patient susceptible to opportunistic infections, unusual cancers, and other abnormalities that define AIDS.

The syndrome was first described by the Centers for disease Control and Prevention (CDC) in 1981. Since then, the CDC has declared a case surveillance definition for AIDS and has modified it several times, most recently in 1993.

Causes

AIDS results from infection with HIV, which strikes cell bearing the CD4+ antigen; the latter (normally a receptor for major histocompatibility complex molecules) serves as a receptor for the retrovirus and lets it enter the cell. HIV prefers to infect the CD4 + lymphocyte or macrophage but may also infect other CD4 + antigen-bearing cells of the GI tract, uterine cervical cells, and neuroglial cells. The virus gains access by binding to the CD4 + molecule on the cell surface along with a coreceptor (thought to be the chemokine receptor CCR5). After invading a cell, HIV replicates, leading to cell death, or becomes latent.

HIV infection leads to profound pathology, either directly, through destruction of CD4 + cells, other immune cells, and neuroglial cells, or indirectly, through the secondary effects of CD4 + T-cell dysfunction and resultant immunosuppression.

Symptoms

The symptoms of AIDS are primarily the result of infections that do not normally develop in individuals with healthy immune systems. These are called opportunistic infections.

Patients with AIDS have had their immune system depleted by HIV and are very susceptible to such opportunistic infections. Common symptoms are fevers, sweats (particularly at night), swollen glands, chills, weakness, and weight loss.

Note: Initial infection may produce no symptoms. Some people with HIV infection remain without symptoms for years between the time of exposure and development of AIDS. However, some people develop what feels like flu about two weeks after contracting the virus.

Diagnostic tests

The CDC defines AIDS as an illness characterized by one or more "indicator" diseases coexisting with laboratory evidence of HIV infection and other possible causes of immunosuppression. The CDC's current AIDS surveillance case definition requires laboratory confirmation of HIV infection in people who have a CD4 + T-cell count of 200 cells/µ1 or who have an associated clinical condition or disease.

Treatment

No cure has yet been found for AIDS; however, primary therapy for HIV infection includes three types of antiretroviral agents:

• protease inhibitors (PIs), such as ritonavir, indinavir, nelfinavir, and saquinavir
• nucleoside reverse transcriptase inhibitors (nRTls), such as zidovudine, didanosine, zalcitabine, lamivudine, and stavudine
• nonnucleoside reverse transcriptase inhibitors (NNR­TIs), such as nevirapine and delavirdine.

These agents, used in various combinations, are designed to inhibit HIV viral replication. Other potential therapies include immunomodulatory agents designed to boost the weakened immune system and anti-infective and antineoplastic agents to combat opportunistic infections and associated cancers; some are used prophylactically to help patients resist opportunistic infections.

Treatment protocols combine two or more agents in an effort to gain the maximum benefit with the fewest adverse reactions. Such regimens typically include one PI plus two nNRTls, or one NNRTI plus two nNRTIs. Many variations and drug interactions are under study. Combination therapy helps to inhibit the production of resistant, mutant strains. Supportive treatments help to maintain nutritional status and relieve pain and other distressing physical and psychological symptoms.

Many pathogens in AIDS respond to anti-infective drugs but tend to recur after treatment ends. For this reason, most patients need continuous anti-infective treatment, presumably for life or until the drug is no longer tolerated or effective.

Treatment with zidovudine has proved effective in slowing the progression of HIV infection, decreasing opportunistic infections, and prolonging survival, but it often produces serious adverse reactions and toxicities. The drug is usually combined with other agents (such as lamivudine) but has also been used as a single agent for pregnant HIV-positive women. The recommendation is to take 100 mg every 4 hours for a total daily dose of 600 mg, or 500 mg if the patient doesn't want to interrupt sleep. Other nRTIs, such as didanosine and zalcitabine, may be used in combination regimens for patients who can't tolerate or no longer respond to zidovudine.

Prevention of AIDS and HIV Infection

The only way to protect from contracting AIDS sexually is to abstain from sex outside of a mutually faithful relationship with a partner whom the person knows is not infected with the AIDS virus. Otherwise, risks can be minimized if they:

• Don't have sexual contact with anyone who has symptoms of AIDS or who is a member of a high risk group for AIDS.
• Avoid contacting blood from injuries or nosebleeds where the HIV status of the bleeding individual is unknown. Protective clothing, masks, and goggles may be appropriate when caring for people who are injured.
• Avoid anal intercourse altogether.
• Get professional help for terminating the drug habit.
• Mothers who are HIV-positive should not breast feed their babies.

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