Home :: HIV AIDS

AIDS And HIV Infection - 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 (T­cell) 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.

This 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.

A retrovirus-the human immunodeficiency virus (HIV) type I - is the primary causative agent. Transmission of HIV occurs by contact with infected blood or body fluids and is associated with identifiable high-risk behaviors. It's therefore disproportionately represented in homosexual and bisexual men, I.V. drug users, neonates of HIV-infected women, recipients of contaminated blood or blood products (dramatically decreased since mid-1985), and heterosexual partners of persons in the former groups. Because of similar routes of transmission, AIDS shares epidemiologic patterns with hepatitis B and sexually transmitted diseases (STDs).

The natural history of AIDS infection begins with infection by the mv retrovirus, which is detectable only by laboratory tests, and ends with the severely immunocompromised, terminal stage of this disease. Depending on individual variations and the presence of cofactors that influence progression, the time elapsed from acute HIV infection to the appearance of symptoms (mild to severe) to the diagnosis of AIDS and, eventually, to death varies greatly. Current combination antiretroviral therapy (for example, with zidovudine, ritonavir, and others) and treatment and prophylaxis of common opportunistic infections can delay the natural progression of HIV disease and prolong survival.

Causes of aids

AIDS results from infection with HIV, which strikes cells 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. mv 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 receptor CCR5). After invading a cell, HIV replicates, leading to cell death, or becomes latent. mv 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.

The infection process takes three forms:

• immunodeficiency (opportunistic infections and unusual cancers).
• autoimmunity (lymphoid interstitial pneumonia, arthritis, hypergamma­globulinemia, and production of autoimmune antibodies)
• neurologic dysfunction (AIDS dementia complex, HIV encephalopathy, and peripheral neuropathies).

Transmission

HIV is transmitted by direct inoculation during intimate sexual contact, especially associated with the mucosal trauma of receptive rectal intercourse; transfusion of contaminated blood or blood products (a risk diminished by routine testing of all blood products); sharing of contaminated needles; or transplacental or postpartum transmission from an infected mother to the fetus (by cervical or blood contact at delivery and in breast milk).

Accumulating evidence suggests that HIV isn't transmitted by casual house­hold or social contact. The average time between exposure to the virus and diagnosis of AIDS is 8 to to years, but shorter and longer incubation times have also been recorded.

Signs and symptoms of aids

HIV infection manifests itself in many ways.

CLINICAL TIP After a high-risk exposure and inoculation, the infected person usually experiences a mononucleosis-like syndrome, which may be attributed to the flu or another virus, and then may remain asymptomatic for years. In this latent stage, the only sign of HIV infection is laboratory evidence of seroconversion.

When symptoms appear, they may take many forms:

• persistent generalized adenopathy
• nonspecific symptoms (weight loss, fatigue, night sweats, fevers)
• neurologic symptoms resulting from HIV encephalopathy.
• pportunistic infection or cancer.

The clinical course varies slightly in children with AIDS. Apparently, their incubation time is shorter with a mean of 17 months. Signs and symptoms resemble those in adults, except for findings related to STDs. Children show virtually all of the opportunistic infections observed in adults, with a higher incidence of bacterial infections: otitis media, sepsis, chronic salivary gland enlargement, Mycobacterium avium complex function, and pneumonias, including Pneumocystis carinii and lymphoid interstitial pneumonias.

Diagnosis

The CDC defines AIDS as an illness characterized by one or more "indicator" diseases coexisting with laboratory evidence of HI V 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/ul or who have an associated clinical condition or disease.

Antibody tests

The most commonly performed tests, antibody tests indicate mv infection indirectly by revealing HIV antibodies. The recommended protocol requires initial screening of individuals and blood products with an enzyme-linked imunosorbent assay (ELISA). A positive ELISA should be repeated and then confirmed by an alternate method, usually the Western blot or an immunofluorescence assay. However, antibody testing isn't always reliable. Because the body takes a variable amount of time to produce a detectable level of antibodies, a "window" varying from a few weeks to as long as 35 months in one documented case allows an HIV-infected person to test negative for HIV anti­bodies.

Antibody tests are also unreliable in neonates because transferred maternal antibodies persist for 6 to 10 months. To overcome these problems, direct testing is performed to detect HIV. Direct tests include antigen tests (p24 antigen), HIV cultures, nucleic acid probes of peripheral blood lymphocytes with determination of HIV-1 ribonucleic acid levels, and the polymerase chain reaction.

Other tests

Additional tests to support the diagnosis and help evaluate the severity of immunosuppression include CD4+ and CD8+ T-lymphocyte subset counts, erythrocyte sedimentation rate, complete blood count, serum betaz-microglobulin, p24 antigen, neopterin levels, and anergy testing. Because many opportunistic infections in AIDS patients are reactivations of previous infections, patients are also tested for syphilis, hepatitis B, tuberculosis, toxoplasmosis and, in some areas, histoplasmosis.

Treatment of aids

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

• protease inhibitors (PIs), such as ritonavir, indinavir, nelfinavir, and saquinavir
• nucleoside reverse transcriptase inhibitors (NRTIs), 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.

Current treatment protocols combine three agents in an effort to gain the maximum benefit with the fewest adverse reactions. Such regimens include one PI and are considered the most effective treatment. Many variations and drug interactions are under study. Combination therapy helps inhibit the production of resistant, mutant strains. Supportive treatments help 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.

Zidovudine

Treatment with zidovudine has proved effective in slowing the progression of HIV infection, decreasing opportunistic infections, and prolonging survival. However, it often produces serious adverse reactions and toxicities. The drug is often combined with other agents (such as lamivudine) but has also been used as a single agent for pregnant HIV­ positive women.

The current 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 also be used in combination regimens for patients who can't tolerate or no longer respond to zidovudine.

Special considerations

• Health care workers and the public are advised to use precautions in all situations that risk exposure to blood, body fluids, and secretions. Diligently practicing standard precautions can prevent the inadvertent transmission of AIDS, hepatitis B, and other infectious diseases that are transmitted by similar routes.

CLINICAL TIP Combination anti retroviral therapy aims to maximally suppress HIV replication, thereby improving survival. However, poor drug compliance may lead to resistance and treatment failure. Patients must understand that medication regimens must be followed closely and may be required for many years, if not throughout life.

• Recognize that a diagnosis of AIDS is profoundly distressing because of the disease's social impact and the discouraging prognosis. The patient may lose his job and financial security as well as the support of family and mends. Coping with an altered body image, the emotional burden of serious illness, and the threat of death may overwhelm the patient.