Signs and symptoms

The symptoms of AIDS are primarily the result of conditions that do not normally develop in individuals with healthy immune systems. Most of these conditions are infections caused by bacteria, viruses, fungi and parasites that are normally controlled by the elements of the immune system that HIV damages.

Opportunistic infections are common in people with AIDS.^[41] These infections affect nearly every organ system.

People with AIDS also have an increased risk of developing various cancers such as Kaposi's sarcoma, cervical cancer and cancers of the immune system known as lymphomas. Additionally, people with AIDS often have systemic symptoms of infection like fevers, sweats (particularly at night), swollen glands, chills, weakness, and weight loss.^[42][43] The specific opportunistic infections that AIDS patients develop depend in part on the prevalence of these infections in the geographic area in which the patient lives.

Pulmonary

Pneumocystis pneumonia (originally known as Pneumocystis carinii pneumonia, and still abbreviated as PCP, which now stands for Pneumocystis pneumonia) is relatively rare in healthy, immunocompetent people, but common among HIV-infected individuals. It is caused by Pneumocystis jirovecii.

Before the advent of effective diagnosis, treatment and routine prophylaxis in Western countries, it was a common immediate cause of death. In developing countries, it is still one of the first indications of AIDS in untested individuals, although it does not generally occur unless the CD4 count is less than 200 cells per µL of blood.^[44]

Tuberculosis (TB) is unique among infections associated with HIV because it is transmissible to immunocompetent people via the respiratory route, and is not easily treatable once identified,^[45] Multidrug resistance is a serious problem. Tuberculosis with HIV co-infection (TB/HIV) is a major world health problem according to the World Health Organization: in 2007, 456,000 deaths among incident TB cases were HIV-positive, a third of all TB deaths and nearly a quarter of the estimated 2 million HIV deaths in that year.^[46]

Even though its incidence has declined because of the use of directly observed therapy and other improved practices in Western countries, this is not the case in developing countries where HIV is most prevalent. In early-stage HIV infection (CD4 count >300 cells per µL), TB typically presents as a pulmonary disease. In advanced HIV infection, TB often presents atypically with extrapulmonary (systemic) disease a common feature. Symptoms are usually constitutional and are not localized to one particular site, often affecting bone marrow, bone, urinary and gastrointestinal tracts, liver, regional lymph nodes, and the central nervous system.^[47]

Gastrointestinal

Esophagitis is an inflammation of the lining of the lower end of the esophagus (gullet or swallowing tube leading to the stomach). In HIV-infected individuals, this is normally due to fungal (candidiasis) or viral (herpes simplex-1 or cytomegalovirus) infections. In rare cases, it could be due to mycobacteria.^[48]

Unexplained chronic diarrhea in HIV infection is due to many possible causes, including common bacterial (Salmonella, Shigella, Listeria or Campylobacter) and parasitic infections; and uncommon opportunistic infections such as cryptosporidiosis, microsporidiosis, Mycobacterium avium complex (MAC) and viruses,^[49] astrovirus, adenovirus, rotavirus and cytomegalovirus, (the latter as a course of colitis).

In some cases, diarrhea may be a side effect of several drugs used to treat HIV, or it may simply accompany HIV infection, particularly during primary HIV infection. It may also be a side effect of antibiotics used to treat bacterial causes of diarrhea (common for Clostridium difficile). In the later stages of HIV infection, diarrhea is thought to be a reflection of changes in the way the intestinal tract absorbs nutrients, and may be an important component of HIV-related wasting.^[50]

Neurological and psychiatric

HIV infection may lead to a variety of neuropsychiatric sequelae, either by infection of the now susceptible nervous system by organisms, or as a direct consequence of the illness itself.^[51]

Toxoplasmosis is a disease caused by the single-celled parasite called Toxoplasma gondii; it usually infects the brain, causing toxoplasma encephalitis, but it can also infect and cause disease in the eyes and lungs.^[52] Cryptococcal meningitis is an infection of the meninx (the membrane covering the brain and spinal cord) by the fungus Cryptococcus neoformans. It can cause fevers, headache, fatigue, nausea, and vomiting. Patients may also develop seizures and confusion; left untreated, it can be lethal.

Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease, in which the gradual destruction of the myelin sheath covering the axons of nerve cells impairs the transmission of nerve impulses. It is caused by a virus called JC virus which occurs in 70% of the population in latent form, causing disease only when the immune system has been severely weakened, as is the case for AIDS patients. It progresses rapidly, usually causing death within months of diagnosis.^[53]

AIDS dementia complex (ADC) is a metabolic encephalopathy induced by HIV infection and fueled by immune activation of HIV infected brain macrophages and microglia. These cells are productively infected by HIV and secrete neurotoxins of both host and viral origin.^[54] Specific neurological impairments are manifested by cognitive, behavioral, and motor abnormalities that occur after years of HIV infection and are associated with low CD4⁺ T cell levels and high plasma viral loads.

Prevalence is 10–20% in Western countries^[55] but only 1–2% of HIV infections in India.^[56][57] This difference is possibly due to the HIV subtype in India. AIDS related mania is sometimes seen in patients with advanced HIV illness; it presents with more irritability and cognitive impairment and less euphoria than a manic episode associated with true bipolar disorder. Unlike the latter condition, it may have a more chronic course. This syndrome is less often seen with the advent of multi-drug therapy.

Tumors

Patients with HIV infection have substantially increased incidence of several cancers. This is primarily due to co-infection with an oncogenic DNA virus, especially Epstein-Barr virus (EBV), Kaposi's sarcoma-associated herpesvirus (KSHV) (also known as human herpesvirus-8 [HHV-8]), and human papillomavirus (HPV).^[58][59]

Kaposi's sarcoma (KS) is the most common tumor in HIV-infected patients. The appearance of this tumor in young homosexual men in 1981 was one of the first signals of the AIDS epidemic. Caused by a gammaherpes virus called Kaposi's sarcoma-associated herpes virus (KSHV), it often appears as purplish nodules on the skin, but can affect other organs, especially the mouth, gastrointestinal tract, and lungs. High-grade B cell lymphomas such as Burkitt's lymphoma, Burkitt's-like lymphoma, diffuse large B-cell lymphoma (DLBCL), and primary central nervous system lymphoma present more often in HIV-infected patients. These particular cancers often foreshadow a poor prognosis. Epstein-Barr virus (EBV) or KSHV cause many of these lymphomas. In HIV-infected patients, lymphoma often arises in extranodal sites such as the gastrointestinal tract.^[60] When they occur in an HIV-infected patient, KS and aggressive B cell lymphomas confer a diagnosis of AIDS.

Invasive cervical cancer in HIV-infected women is also considered AIDS-defining, it is caused by human papillomavirus (HPV).^[61]

In addition to the AIDS-defining tumors listed above, HIV-infected patients are at increased risk of certain other tumors, notably Hodgkin's disease, anal and rectal carcinomas, hepatocellular carcinomas, head and neck cancers, and lung cancer. Some of these are causes by viruses, such as Hodgkin's disease (EBV), anal/rectal cancers (HPV), head and neck cancers (HPV), and hepatocellular carcinoma (hepatitis B or C). Other contributing factors include exposure to carcinogens (cigarette smoke for lung cancer), or living for years with subtle immune defects.

Interestingly, the incidence of many common tumors, such as breast cancer or colon cancer, does not increase in HIV-infected patients. In areas where HAART is extensively used to treat AIDS, the incidence of many AIDS-related malignancies has decreased, but at the same time malignant cancers overall have become the most common cause of death of HIV-infected patients.^[62] In recent years, an increasing proportion of these deaths have been from non-AIDS-defining cancers.

Other infections

AIDS patients often develop opportunistic infections that present with non-specific symptoms, especially low-grade fevers and weight loss. These include opportunistic infection with Mycobacterium avium-intracellulare and cytomegalovirus (CMV). CMV can cause colitis, as described above, and CMV retinitis can cause blindness.

Penicilliosis due to Penicillium marneffei is now the third most common opportunistic infection (after extrapulmonary tuberculosis and cryptococcosis) in HIV-positive individuals within the endemic area of Southeast Asia.^[63]

An infection that often goes unrecognized in AIDS patients is Parvovirus B19. Its main consequence is anemia, which is difficult to distinguish from the effects of antiretroviral drugs used to treat AIDS itself.^[64]

History and origin

AIDS was first reported June 5, 1981, when the U.S. Centers for Disease Control (CDC) recorded a cluster of Pneumocystis carinii pneumonia (now still classified as PCP but known to be caused by Pneumocystis jirovecii) in five homosexual men in Los Angeles.^[14] In the beginning, the CDC did not have an official name for the disease, often referring to it by way of the diseases that were associated with it, for example, lymphadenopathy, the disease after which the discoverers of HIV originally named the virus.^[15][16] They also used Kaposi's Sarcoma and Opportunistic Infections, the name by which a task force had been set up in 1981.^[17]

In the general press, the term GRID, which stood for Gay-related immune deficiency, had been coined.^[18] The CDC, in search of a name, and looking at the infected communities coined “the 4H disease,” as it seemed to single out Haitians, homosexuals, hemophiliacs, and heroin users.^[19] However, after determining that AIDS was not isolated to the homosexual community,^[17] the term GRID became misleading and AIDS was introduced at a meeting in July 1982.^[20] By September 1982 the CDC started using the name AIDS, and properly defined the illness.^[21]

The earliest known positive identification of the HIV-1 virus comes from the Congo in 1959 and 1960 though genetic studies indicate that it passed into the human population from chimpanzees around fifty years earlier.^[11] A recent study states that a strain of HIV-1 probably moved from Africa to Haiti and then entered the United States around 1969.^[22]

The HIV virus descends from the related simian immunodeficiency virus (SIV), which infects apes and monkeys in Africa. There is evidence that humans who participate in bushmeat activities, either as hunters or as bushmeat vendors, commonly acquire SIV.^[23] However, only a few of these infections were able to cause epidemics in humans, and all did so in the late 19^th—early 20^th century. To explain why HIV became epidemic only by that time, there are several theories, each invoking specific driving factors that may have promoted SIV adaptation to humans, or initial spread: social changes following colonialism,^[24] rapid transmission of SIV through unsafe or unsterile injections (that is, injections in which the needle is reused without being sterilised),^[25] colonial abuses and unsafe smallpox vaccinations or injections,^[26] or prostitution and the concomitant high frequency of genital ulcer diseases (such as syphilis) in nascent colonial cities.^[27][28] See the main article Origin of AIDS.

One of the first high profile victims of AIDS was the American actor Rock Hudson, a known homosexual who had been married and divorced earlier in life, who died on 2 October 1985 having announced that he was suffering from the virus on 25 July that year. It had been diagnosed during 1984.^[29] A notable British casualty of AIDS that year was Nicholas Eden, a Member of Parliament and son of the late prime minister Anthony Eden.^[30] Eden junior, a lifelong batchelor, was also a known homosexual.^[31] The virus claimed perhaps its most famous victim yet on 24 November 1991, when British rock star Freddie Mercury, lead singer of the band Queen, died from an AIDS related illness having only announced that he was suffering from the illness the previous day;^[32] however he had been diagnosed as HIV positive during 1987.^[33] One of the first high profile heterosexual victims of the virus was Arthur Ashe, the American tennis player. He was diagnosed as HIV positive on 31 August 1988, having contracted the virus from blood transfusions during heart surgery earlier in the 1980s. Further tests within 24 hours of the initial diagnosis revealed that Ashe had AIDS, but he did not tell the public about his diagnosis until April 1992.^[34] He died, aged 49, as a result of the AIDS virus on 6 February 1993.^[35]

A more controversial theory known as the OPV AIDS hypothesis suggests that the AIDS epidemic was inadvertently started in the late 1950s in the Belgian Congo by Hilary Koprowski's research into a poliomyelitis vaccine.^[36][37] According to scientific consensus, this scenario is not supported by the available evidence.^[38][39][40]

AIDS

Acquired immune deficiency syndrome or acquired immunodeficiency syndrome (AIDS) is a disease of the human immune system caused by the human immunodeficiency virus (HIV).^[1][2][3] This condition progressively reduces the effectiveness of the immune system and leaves individuals susceptible to opportunistic infections and tumors. HIV is transmitted through direct contact of a mucous membrane or the bloodstream with a bodily fluid containing HIV, such as blood, semen, vaginal fluid, preseminal fluid, and breast milk.^[4][5] This transmission can involve anal, vaginal or oral sex, blood transfusion, contaminated hypodermic needles, exchange between mother and baby during pregnancy, childbirth, breastfeeding or other exposure to one of the above bodily fluids.

AIDS is now a pandemic.^[6] As of 2009, AVERT estimated that there are 33.3 million people worldwide living with HIV/AIDS, with 2.6 million new HIV infections per year and 1.8 million annual deaths due to AIDS.^[7] In 2007, UNAIDS estimated: 33.2 million people worldwide had AIDS that year; AIDS killed 2.1 million people in the course of that year, including 330,000 children, and 76% of those deaths occurred in sub-Saharan Africa.^[8] According to UNAIDS 2009 report, worldwide some 60 million people have been infected, with some 25 million deaths, and 14 million orphaned children in southern Africa alone since the epidemic began.^[9]

Genetic research indicates that HIV originated in west-central Africa during the late nineteenth or early twentieth century.^[10][11] AIDS was first recognized by the U.S. Centers for Disease Control and Prevention in 1981 and its cause, HIV, identified in the early 1980s.^[12]

Although treatments for AIDS and HIV can slow the course of the disease, there is no known cure or vaccine. Antiretroviral treatment reduces both the mortality and the morbidity of HIV infection, but these drugs are expensive and routine access to antiretroviral medication is not available in all countries.^[13] Due to the difficulty in treating HIV infection, preventing infection is a key aim in controlling the AIDS pandemic, with health organizations promoting safe sex and needle-exchange programmes in attempts to slow the spread of the virus. (wikipedia.org/wiki/AIDS)