Akademik

A deficiency of cellular immunity induced by infection with the human immunodeficiency virus (HIV-1) and characterized by opportunistic diseases, including Pneumocystis carinii pneumonia, Kaposi sarcoma, oral hairy leukoplakia, cytomegalovirus disease, tuberculosis, Mycobacterium avium complex (MAC) disease, candidal esophagitis, cryptosporidiosis, isosporiasis, cryptococcosis, non-Hodgkin lymphoma, progressive multifocal leukoencephalopathy (PML), herpes zoster, and lymphoma. HIV is transmitted from person to person in cell-rich body fluids (notably blood and semen) through sexual contact, sharing of contaminated needles (as by IV drug abusers), or other contact with contaminated blood (as in accidental needle sticks among health care workers). The primary targets of HIV are cells with the CD4 surface protein, including principally helper T lymphocytes. Antibody to HIV, which appears in the serum 6 weeks to 6 months after infection, serves as a reliable diagnostic marker but does not bind or inactivate HIV. Gradual decline in the CD4 lymphocyte count, typically occurring over a period of 10–12 years, culminates in loss of ability to resist opportunistic infections; the appearance of one or more of these defines the onset of A.. In some patients, generalized lymphadenopathy, fever, weight loss, dementia, and chronic diarrhea are associated with early stages of the disease. A. is uniformly lethal, most patients dying of one or more opportunistic infections or their complications within 2–5 years of the onset of symptoms. In the U.S., A. is the leading cause of death among men 25–44, and the fourth leading cause among women in the same age group. During the past 5 years, the mortality of the disease and rates of perinatal transmission have declined substantially, as has transmission among homosexual men and intravenous drug users. Meanwhile heterosexual transmission and case rates among blacks and Hispanics have increased. Some 50 million people are estimated to be infected worldwide, with the highest incidence in some Central and East African countries, where as many as 25% of the adult population may be HIV-positive. Besides prophylaxis against opportunistic infection, standard therapy of HIV infection includes use of nucleoside analogs (didanoxine, lamivudine, ribavirin, stavudine, zidovudine), nonnucleoside reverse transcriptase inhibitors (delavirine, efavirenz, nevirapine), and protease inhibitors (crixivan, indinavir, ritonavir, saquinavir). SEE ALSO: human immunodeficiency virus. SYN: acquired immunodeficiency syndrome. [acronym, acquired immunodeficiency syndrome] The development of effective antiretroviral agents (reverse transcriptase inhibitors and protease inhibitors) and of quantitative plasma HIV RNA assays that can monitor progression of disease and response to treatment has shifted the goal of management in A. from prophylaxis and treatment of opportunistic infections to achievement of remission through suppressive therapy. Immune compromise is monitored by serial CD4 counts; viral replication, by plasma HIV RNA assay (viral load). Indications for starting antiretroviral therapy are the appearance of symptoms of opportunistic infection, decline of the CD4 count below 500/mm₃, or viral load exceeding 5000 copies/mL. Protease inhibitors have been shown to be highly effective antiretroviral agents, and standard treatment regimens combining 2 reverse transcriptase inhibitors with 1 protease inhibitor (“triple therapy”) have clearly demonstrated superiority over monotherapy. However, these drugs are expensive; in 2000 the annual cost of therapy and monitoring exceeded $10,000. Regimens are often complex, with varying requirements for fasting and timing of doses, and adverse effects and drug interactions are common. Protease inhibitors have been associated with elevation of cholesterol and triglycerides, insulin resistance, and disfiguring lipodystrophy. Strains of HIV resistant to all available protease inhibitors have appeared. The rationale for current A. regimens is an effort to eradicate HIV infection by inhibiting spread of virus to new cells until all infected cells have died. However, no one has ever been cured of A.. A small number of resting CD4 memory cells in treated patients with undetectable plasma HIV RNA levels harbor HIV proviral DNA capable of replication, and these cells may survive for months or years. Macrophages and CNS neurons may serve as an anatomic sanctuary for HIV to which antiretroviral drugs cannot penetrate in adequate concentration. When antiretroviral therapy is initiated early, CD4 helper cell counts rise, CD4 cell activity is preserved, and HIV RNA levels may remain undetectable for long periods. However, in about 50% of patients with advanced disease, even multidrug regimens fail to suppress plasma viral RNA to undetectable levels. Many treatment failures result from poor compliance with multidrug regimens. One-fourth of patients queried admit to allowing themselves occasional “drug holidays.” Failure of one therapeutic regimen often precludes success with others because of the high degree of cross-resistance among antiretroviral drugs. After failure of an initial regimen, genotypic testing can be used to identify mutations in the HIV genome that confer resistance to one or more classes of HIV drugs. In a significant number of patients, opportunistic infections continue despite restoration of CD4 counts, probably because some T-cell subpopulations have been annihilated by HIV infection and are not recoverable even after viral suppression. Hence prophylaxis against opportunistic infections remains an essential component of the management of HIV disease. Moreover, even HIV-infected persons with undetectable viral loads must still be considered infectious. Evolving standards of treatment in HIV disease include aggressive therapy of the acute phase of infection and prophylactic administration of antiretroviral therapy after accidental needlestick or sexual assault. Efforts to develop a vaccine against HIV have been hampered by the unique properties of the virus and the long incubation period of A.. A bivalent vaccine that elicits antibody to the outer shell protein of HIV is in Phase III trials. Many authorities believe that an effective vaccine must also stimulate cell-mediated immunity.

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AIDS 'ādz n a disease of the human immune system that is characterized cytologically esp. by a reduction in the numbers of CD4-bearing helper T cells to 20 percent or less of normal thereby rendering the subject highly vulnerable to life-threatening conditions (as Pneumocystis carinii pneumonia) and to some that become life threatening (as Kaposi's sarcoma) and that is caused by infection with HIV commonly transmitted in infected blood esp. during illicit intravenous drug use and in bodily secretions (as semen) during sexual intercourse called also acquired immune deficiency syndrome, acquired immunodeficiency syndrome

a syndrome first identified in Los Angeles in 1981; a description of the causative virus - the human immunodeficiency virus (HIV) - was available in 1983. The virus destroys a subgroup of lymphocytes, the helper T-cell (or CD4 lymphocytes), resulting in suppression of the body's immune response (see immunity). AIDS is essentially a sexually transmitted disease, either homosexually or heterosexually. The two other main routes of spread are via infected blood or blood products (current processing of blood for transfusion and for haemophiliacs has virtually eliminated this danger) and by the maternofetal route. The virus may be transmitted from an infected mother to the child in the uterus or it may be acquired from maternal blood during parturition; it may also be transmitted in breast milk.

Acute infection following exposure to the virus results in the production of anti-bodies (seroconversion), their presence indicating that infection has taken place. However, not all those who seroconvert progress to chronic infection. For those who do enter a chronic stage there may be illness of varying severity, including persistent generalized involvement of the lymph nodes; what is termed AIDS-related complex (ARC), including intermittent fever, weight loss, diarrhoea, fatigue, and night sweats; and AIDS itself, presenting as opportunistic infections (especially pneumonia caused by the protozoan Pneumocystis carinii) and/or tumours, such as Kaposi's sarcoma.

HIV has been isolated from semen, cervical secretions, plasma, cerebrospinal fluid, tears, saliva, urine, and breast milk but the concentration shows wide variations. Moreover HIV is a fragile virus and does not survive well outside the body. It is therefore considered that ordinary social contact with HIV-positive subjects involves no risk of infection. However, high standards of clinical practice are required by all health workers in order to avoid inadvertent infection via blood, blood products, or body fluids from HIV-positive people. Staff who become HIV-positive are expected to declare their status and will be counselled.

Until recently, AIDS has been considered to be universally fatal, although the type and length of illness preceding death varies considerably. The development of antiviral drugs, initially used singly but more recently used in dual or triple combinations, may well modify the gloomy outlook. These drugs include the reverse transcriptase inhibitors and the protease inhibitor.