A deficiency of cellular immunity induced by infection with the human immunodeficiency virus (HIV-1) and characterized by opportunistic diseases, including Pneumocystis jiroveci (formerly carinii) pneumonia, Kaposi sarcoma, oral hairy leukoplakia, cytomegalovirus disease, tuberculosis, Mycobacterium avium complex (MAC) disease, candidal esophagitis, cryptosporidiosis, isoporiasis, 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 infected blood (as in accidental needlesticks among health care workers). Maternal-fetal transmission also occurs. 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 infections defines the onset of AIDS. In some patients, generalized lymphadenopathy, fever, weight loss, dementia, or chronic diarrhea occurs much earlier in the course of the infection. Untreated AIDS is uniformly lethal within 2–5 years after the first appearance of an opportunistic infection. Besides prophylaxis against opportunistic infection, standard therapy of HIV infection includes use of nucleoside analogues (e.g., didanosine, lamivudine, ribavirin, stavudine, zipovudine), nonnucleoside reverse transcriptase inhibitors (e.g., delavirine, efavirenz, nevirapine) and protease inhibitors (e.g., atazanavir, crixivan, indinavir, ritonavir, saquinavir).
Each year about 5 million people contract AIDS worldwide, and 3 million die of it. Some 40–50 million are estimated to be living with the disease. The gender incidence is approximately equal. The highest prevalence is in some African countries, where as many as 25% of the adult population may test HIV positive; about 70% of the world's infected population lives in sub-Saharan Africa. The first cases of AIDS were reported in the U.S. in June 1981. During the succeeding 2 decades an estimated 1.4 million people in this country were infected with HIV and 816,149 cases of AIDS and 467,910 deaths were reported to the U.S. Centers for Disease Control and Prevention (CDC). The numbers of new AIDS cases and deaths declined substantially after introduction of combination antiretroviral therapy in the late 1990s. The annual number of new cases of AIDS in the U.S. has remained stable at about 40,000, with 16,000 deaths since 1998. The number of people infected with HIV continues to increase, and of an estimated 1 million, one fourth are unaware that they are infected. In the U.S., AIDS is the leading cause of death among men 25–44 years old, and the fourth leading cause of death among women in the same age group. The development of effective antiretroviral agents (e.g., 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 AIDS 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 (i.e., plasma viral load, PVL). Indications for starting antiretroviral therapy are the appearance of symptoms of opportunistic infection, decline of the CD4 count below 350/mm3, or viral load exceeding 30,000 copies/mL. The CD4 count is considered a more sensitive predictor of disease progression than viral load. Empiric treatment may be begun early (within 6 months after conversion to HIV-positive status) in an effort to preserve immune function and mobilize the patient's own defenses against the virus. But current guidelines advise deferring treatment as long as possible so as to limit induction of drug resistance. 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. These drugs are expensive. 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. In one large study, more than one half of HIV-infected adults under treatment were found to be infected with strains of virus resistant to one or more antiretroviral drugs, and strains of HIV that are resistant to all available protease inhibitors have appeared. The rationale for current AIDS regimens is an effort to eradicate HIV infection by inhibiting spread of virus to new cells until all infected cells have died. However, actual cure seldom if ever occurs. 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 into which antretroviral 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. But 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. 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. Many patients remain vulnerable to opportunistic infections despite restoration of CD4 counts to normal, probably because some subpopulations of T cells have been annihilated and cannot be recovered even after HIV has been suppressed. Moreover, even HIV-infected patients with undetectable viral loads must still be considered infectious. In a small set of those infected with HIV, impairment of immunity progresses to AIDS slowly or not at all. CD8 T-cells from such nonprogressors have been found to produce proteins called )-defensins. Evolving standards of treatment in HIV disease include aggressive prophylaxis in pregnancy and after accidental needle stick and sexual assault. Administration of antiretroviral agents to HIV-positive mothers before birth and during labor and delivery, and to newborns for the first 6 weeks of life, markedly decrease the risk of vertical transmission of HIV infection. The risk of HIV infection after occupational parenteral exposure to blood from an HIV-infected patient is approximately 0.3%. Postexposure prophylaxis with antiretroviral agents continued for 28 days have been shown to reduce the risk by 80%. The selection of agents depends on the source patient's therapeutic history. Efforts to develop a vaccine against HIV have been hampered by the unique properties of the virus and the long incubation period of AIDS. Early in the 21st century, public health authorities sought to make HIV testing a routine part of medical care, to facilitate diagnosis outside formal clinical settings, to prevent new infections by educating people and their sexual partners, and to decrease perinatal HIV transmission through routine HIV testing of pregnant women and of infants whose mothers were not screened.
Reference: Stedman's Medical Dictionary.