An advanced stage (technically, the third stage) of infection with HIV (human immunodeficiency virus).
AIDS was unrecognized before 1981, but it is now one of the most common causes of death worldwide. Most people with AIDS are between 15 and 44 years old, are poor, and are heterosexual. Most have limited access to good care and live in resource-poor nations in Africa and Asia. Worldwide about 2.3 million new HIV infections occur each year. More than 33 million people live with HIV infection. Annual mortality is about 5.5%, and about 1.8 million people die of HIV/AIDS annually. Total infections worldwide is 78 million. Total deaths worldwide is 35 million. In the U.S., more than 1.2 million people are living with HIV/AIDS, and about 40,000 Americans are infected annually. Approximately half of the infected are unaware of their condition. The primary risk groups for HIV/AIDS are people who have unprotected sexual intercourse, injection drug users, men who have sex with men, women and men with multiple sexual partners, and children of infected mothers.
Two human immunodeficiency viruses, HIV-1 and HIV-2, have been identified. Both cause AIDS, but infection with HIV-2 has been primarily limited to West Africa. Infection occurs when a viral envelope glycoprotein (gp120) binds to CD4 receptors and coreceptors (called CXCR4 and CCR5) on lymphocytes, macrophages, and other immune system cells, causing viral uptake and, eventually, cellular destruction and immune system dysfunction. HIV is a retrovirus that uses the enzyme reverse transcriptase to convert its viral RNA to viral DNA. The viral DNA incorporates into the host cell DNA and is transcribed and translated by host cells. New viral proteins are created and assembled into virions by the viral enzyme protease. About 100 billion virions, many with minor but protective mutations, are created during each reproductive cycle of HIV. Most newly formed viruses quickly infect circulating immune cells or take up residence in body reservoirs that are relatively inaccessible to drug therapy. The ability of HIV to mutate and evade treatment has made drug management of the disease complicated and has hindered development of a vaccine. Nonetheless, treatment with combinations of drugs (see below) decreases both the severity of infection and the development of drug-resistant clones and prolongs disease-free survival. The destruction of cells needed for normal immunological function produces susceptibility to diseases that the body normally resists. This susceptibility is the hallmark of AIDS. In the U.S., common pathogens that infect AIDS patients include Pneumocystis carinii (also known as P. jiroveci), Mycobacterium avium intracellulare (MAI), cytomegalovirus, Toxoplasma gondii, Candida albicans, Cryptosporidium, and Histoplasma capsulatum. AIDS patients are also susceptible to nonopportunistic infections (such as tuberculosis, syphilis, herpesvirus infection, papillomavirus infections, and streptococcal pneumonia) at rates and with a virulence far exceeding those in the general population.
SYMPTOMS AND SIGNS
Primary exposure to HIV is known as Stage 1 of the disease. It typically causes a severe, influenza-like infection, with fever, sore throat, swollen glands and muscle and joint pains. Stage 1 is followed by seroconversion (the presence of HIV antibodies in the bloodstream). In Stage 2 of HIV/AIDS (latent infection), the virus multiplies in the body but causes no symptoms other than enlargement of lymph nodes. In Stage 3, symptoms and signs begin to develop. These typically include oral thrush, oral hairy leukoplakia, weight loss, diarrhea, fever, anemia, and thrombopeni. The opportunistic infections that accompany Stage 4 AIDS (such as Pneumocystis pneumonia) cause fatigue, fevers, chills, sweats, breathlessness, oral ulceration, difficulties with swallowing, pneumonia, diarrhea, skin rashes, anorexia, weight loss, confusion, dementia, and strokelike symptoms. Many people are so incapacitated by AIDS that they are unable to carry out normal activities of daily living; others have very few limitations but may periodically experience life-threatening illnesses. SEE TABLE: Clinical Conditions and Opportunistic Infections Indicating AIDS
The presence of antibodies to HIV indicates infection. Criteria for the diagnosis of AIDS include HIV infection with 1) a CD4+ helper T-cell count of less than 200 cells/mL, or 2) infection with an opportunistic pathogen, and/or 3) the presence of an AIDS-defining malignancy. Enzyme-linked immunosorbent assays (ELISA) or enzyme immunoassays (EIA) are the primary tests used to screen for HIV antibodies. These tests are sensitive but not specific for HIV infection. If antibodies are detected by enzyme immunoassays, a more specific Western blot test is required for confirmation. Point-of-care tests for HIV (in which samples of whole blood, plasma, or oral fluids are used) provide rapid results. Nucleic acid amplification testing (NAAT), polymerase chain reaction (PCR) tests, and monoclonal antibodies to viral p24 antigen can also be used to detect HIV infection. A PCR assay to detect viral RNA can be helpful in identifying acute infection because seroconversion to positive antibody status may not be detectable for two weeks after exposure to the virus. Measurement of the absolute levels of helper T cells (CD4+ T lymphocytes) and the level of HIV viremia (the viral load) are the principal tests used to monitor the course of established infection and the effectiveness of administered therapies. Many health care agencies, such as the Centers for Disease Control and Prevention and the U.S. Veterans Administration recommend routine screening for HIV/AIDS in broad segments of the population to identify and diagnose the disease in asymptomatic patients. Mass screening in the U.S. is likely to be most cost-effective in large urban areas where the vast majority of Americans infected with HIV live. In the U.S., new AIDs diagnoses are much more common in Florida, Georgia, Texas, North Carolina, and the other states of the Southeast in addition to New York, Illinois, New Jersey, Maryland, Washington, D.C., and the rest of the Mid-Atlantic states; and California. AIDS is uncommon in Montana, Idaho, Utah, Nevada, Colorado, the Dakotas, rural parts of Alaska, and Iowa.
Between 60% and 80% of HIV-infected patients develop AIDS within 10 years of seroconversion.
HIV infection is spread by direct contact with the blood or bodily secretions of those infected, usually through a break in the skin or across mucous membranes. In most cases, it has been transmitted from person to person by one of three modes: sexually, by injection of blood products, or from mother to fetus (or mother to infant). All pregnant women should be counseled about testing for the presence of HIV antibodies to prevent maternal-child disease transmission. Antiretroviral therapies during and immediately after pregnancy greatly reduce the vertical transmission of HIV. The third mode of transmission concerns those who engage in unsafe sex or inject drugs with contaminated needles; they are at the greatest risk for contracting the disease. Abstinence from such behavior helps prevent the spread of the disease. Scrupulous screening of the blood supply and of organ donors has dramatically reduced iatrogenic HIV transmission. To date, no vaccine has proved effective in preventing the spread of the disease.
The use of highly active antiretroviral therapies (HAART), typically including two drugs that block viral nucleoside reverse transcriptases (NRTI), in addition to a non-NRTI, an integrase inhibitor, or a protease inhibitor has revolutionized the treatment of HIV/AIDS. Combination-drug “cocktails” can decrease viral loads to undetectable levels and restore a level of immunological function to AIDS patients that, although imperfect, protects against most opportunistic infections. The timing of the initiation of antiretroviral therapy depends on the public health resources available for HIV/AIDS treatment and the stage and patient-specific disease presentation. In developed nations, antiretroviral therapy should begin when an AIDS-defining illness is experienced, when HIV-related renal disease is detected, or in patients who are coinfected with hepatitis B virus. The CD4 cell count level that should trigger antiretroviral treatment is uncertain. Clinical benefit may begin at levels as high as 500 cells/mL; mortality benefit is found at 200 cells/mL; but some experts recommend starting treatment at a level of 350. The potential of antiretroviral therapies is realized only when patients strictly adhere to their prescription regimens and avoid behavior that may place others at risk for disease transmission. Treatments for established AIDS are also directed against the opportunistic infections of AIDS. These include drugs such as trimethoprim/sulfamethoxazole or pentamidine for Pneumocystis carinii pneumonia (P. jiroveci), clarithromycin and other antimicrobial agents for Mycobacterium avium intracellulare, valganciclovir and/or other antivirals for cytomegalovirus, and antifungal drugs (such as intraconazole and amphotericin) for histoplasmosis (Histoplasma capsulatum). Treatment for AIDS-related malignancies includes antiretroviral therapy (augmented by anthracyclines or paclitaxel) for Kaposi sarcoma, and combination chemotherapies (administered systemically or regionally) for non-Hodgkin lymphoma. About 10% of patients with HIV/AIDS die of cardiovascular disease. Cardiovascular risk factor reduction, including the use of lipid-lowering therapies, is a necessary component of therapy for those living with the disease.
Standard infection control precautions prevent the spread of HIV/AIDS to health care providers. Occupational exposure to body fluids from AIDS patients is relatively common in health care, but transmission of the disease is rare. The risk of HIV infection after a puncture wound from a contaminated needle is estimated to be about 0.3%; the risk of seroconversion after mucous membranes are splashed with contaminated blood or body fluids is 0.09%. Postexposure prophylaxis should be given to exposed people as soon as is feasible, typically with a regimen of three drugs taken for 28 days. The virus does not proliferate or readily survive outside the body, i.e., on counters or other surfaces.
Health care professionals should contribute actively to the education of patients about preventing the spread of HIV. Complex treatment regimens make management of the disease a burden for many patients, but they must be encouraged to adhere to these complicated drug regimens because failure to do so may result in the evolution of drug-resistant viruses. Health care providers should anticipate, assess, and assist patients to collaborate in helping to prevent inconsistent drug dosing or abandonment of treatment. The cost of drug therapy and other services may be a factor in adhering to medication. Health care providers should be aware of referral agencies and resources for help in obtaining social service support; information about the disease; funds for housing, food, and medication; and inpatient, outpatient, and hospice care (when appropriate). Health care providers should also be familiar with support groups for partners and families of patients with HIV/AIDS. The effectiveness of contemporary antiretroviral regimens allows adherent patients to live, on average, 3 to 4 decades after diagnosis. The disease now has a better prognosis than many other chronic illnesses.
Severe immunosuppression in HIV infection evidenced only by a very low CD4 helper cell count (less than 200 cells/mm3). Patients have not yet had an opportunistic infection but are highly likely to contract one.
Infection with HIV as a result of vertical transmission of the virus from an infected mother. Worldwide, in 2002, 1500 children were infected every day by maternal to child transmission of the disease; the overwhelming majority of these children live in developing nations. In the U.S. between 1992 and 1997, testing pregnant women to identify HIV infection and treating affected people with zidovudine decreased the risk of perinatal AIDS by about 70%.
Transmission of HIV to infants occurs in utero, during labor and delivery, and through breastfeeding. Approx. 50% to 70% of infants are infected during childbirth, esp. during preterm birth with prolonged rupture of membranes; 30% to 50% are infected in utero; 20% of HIV-positive mothers can transmit the infection through breastfeeding.
The diagnosis is made through two positive blood test results for the presence of HIV or the growth of HIV in culture. Transmission is unlikely to occur in women whose viral load of HIV RNA has been reduced by effective antiretroviral therapy. The Centers for Disease Control and Prevention (CDC) recommends that all adults aged 13 to 64 years should be offered routine HIV testing (with the choice to opt out), as opposed to testing only those patients with known risk factors for the disease.
SYMPTOMS AND SIGNS
Infants may be asymptomatic even when infected with HIV. Infection is monitored by measuring the absolute CD4+ T-cell count, measuring the amount of virus in the blood (viral load), and assessing for the presence of opportunistic infections in infancy or early childhood. Over time, the infected infant may present with Pneumocystis carinii (P. jiroveci) pneumonia, chronic diarrhea, recurrent bacterial infections, failure to thrive, developmental delays, and recurrent Candida and herpes simplex infections. The majority of perinatally infected children develop an AIDS-defining illness by the age of 4. Anemia and neutropenia may occur as side effects of drug therapy.
Zidovudine (AZT) is given for 6 weeks to all infants born of HIV-positive mothers. Prophylaxis for P. carinii (P. jiroveci) pneumonia with trimethoprim-sulfamethoxazole begins at 6 weeks and continues for 6 months in children whose HIV test results are negative and for 1 year in infected infants. The use of highly active antiretroviral therapy (HAART) is being studied. Breastfeeding is contraindicated for all HIV-infected mothers to minimize the risk of transmission of the virus.
Women in their childbearing years who engage in high-risk behavior and whose husbands or primary sexual partner may engage in high-risk behavior should be counseled to be tested for HIV before becoming pregnant or as soon as they know they are pregnant in order to reduce the risk of infecting the fetus or infant. Women who are HIV-positive should begin antiretroviral therapy immediately. Standard precautions are used with babies born of HIV-positive mothers until diagnostic tests indicate that they are not infected. Mothers and other care providers must be instructed in the use of these precautions and to watch for and quickly report respiratory infections.
Clinical Conditions and Opportunistic Infections Indicating AIDS
|AIDS wasting syndrome||Kaposi sarcoma|
|Candida infections (candidiasis) of the trachea, bronchi, lungs, or esophagus||Leukoencephalopathy, progressive multifocal|
|Cervical cancer, invasive||Lymphoma: Burkitt; immunoblastic; non-Hodgkin; primary brain|
|Cryptococcus neoformans: Extrapulmonary infections||Mycobacterium avium complex or M. kansasii: Extrapulmonary or disseminated infections|
|Cryptosporidium: Chronic (lasting more than a month) infections of the GI tract*||Mycobacterium tuberculosis: Pulmonary or extrapulmonary infections|
|Cytomegalovirus: Infections other than those in the liver, spleen, or lymph nodes; cytomegalovirus retinitis with loss of vision||Mycobacterium, other species: Extrapulmonary or disseminated infections|
|Encephalopathy, HIV-related||Pneumonia, Pneumocystis carinii|
|Herpes simplex: Chronic (lasting more than a month) oral ulcers, bronchitis, pneumonitis, or esophagitis||Pneumonia, recurrent|
|Histoplasma capsulatum: Extrapulmonary or disseminated histoplasmosis infections||Toxoplasma gondii: Infections (toxoplasmosis) of the brain, heart, or lung|
|Isosporiasis, chronic (lasting more than a month) intestinal|