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Main article: Psychological aspects of AIDS
Main article: Psychological issues with antiretroviral drug use in HIV/AIDS

Acquired immunodeficiency syndrome, or acquired immune deficiency syndrome (or acronym AIDS or Aids), is a collection of symptoms and infections resulting from the specific damage to the immune system caused by infection with the human immunodeficiency virus (HIV).[1] It results from the latter stages of advanced HIV infection in humans, thereby leaving compromised individuals prone to opportunistic infections and tumors. Although treatments for both AIDS and HIV exist to slow the virus' progression in a human patient, there is no known cure.

Most researchers believe that HIV originated in sub-Saharan Africa [2] during the twentieth century; it is now a global epidemic. UNAIDS and the World Health Organization (WHO) estimate that AIDS has killed more than 25 million people since it was first recognized on December 1, 1981, making it one of the most destructive pandemics in recorded history. In 2005 alone, AIDS claimed between an estimated 2.8 and 3.6 million, of which more than 570,000 were children.[3] In countries where there is access to antiretroviral treatment, both mortality and morbidity of HIV infection have been reduced [4]. However, side-effects of these antiretrovirals have also caused problems such as lipodystrophy, dyslipidaemia, insulin resistance and an increase in cardiovascular risks [5]. The difficulty of consistently taking the medicines has also contributed to the rise of viral escape and resistance to the medicines [6].

Red ribbon

The Red Ribbon is the global symbol for solidarity with HIV-positive people and those living with AIDS.

Infection by HIVEdit

HIV-budding

Scanning electron micrograph of HIV-1 budding from cultured lymphocyte.

AIDS is the most severe manifestation of infection with HIV. HIV is a retrovirus that primarily infects vital components of the human immune system such as CD4+ T cells, macrophages and dendritic cells. It also directly and indirectly destroys CD4+ T cells. As CD4+ T cells are required for the proper functioning of the immune system, when enough CD4+ cells have been destroyed by HIV, the immune system barely works, leading to AIDS. Acute HIV infection progresses over time to clinical latent HIV infection and then to early symptomatic HIV infection and later, to AIDS, which is identified on the basis of the amount of CD4 positive cells in the blood and the presence of certain infections.

For more details on this topic, see HIV.

In the absence of antiretroviral therapy, progression from HIV infection to AIDS occurs at a median of between nine to ten years and the median survival time after developing AIDS is only 9.2 months [7]. However, the rate of clinical disease progression varies widely between individuals, from two weeks up to 20 years. Many factors affect the rate of progression. These include factors that influence the body's ability to defend against HIV, including the infected person's genetic inheritance, general immune function [8][9], access to health care, age and other coexisting infections [7][10][11]. Different strains of HIV [12][13] may also cause different rates of clinical disease progression.

For more details on this topic, see HIV Disease Progression Rates.

DiagnosisEdit

AIDS and HIV case definitionsEdit

Since June 18, 1981, many different definitions have been developed for epidemiological surveillance such as the Bangui definition and the 1994 expanded World Health Organization AIDS case definition. However, these were never intended to be used for clinical staging of patients, for which they are neither sensitive nor specific. The World Health Organizations (WHO) staging system for HIV infection and disease, using clinical and laboratory data, can be used in developing countries and the Centers for Disease Control (CDC) Classification System can be used in developed nations.

WHO Disease Staging System for HIV Infection and DiseaseEdit

Main article: WHO Disease Staging System for HIV Infection and Disease

In 1990, the World Health Organization (WHO) grouped these infections and conditions together by introducing a staging system for patients infected with HIV-1 [14]. This was updated in September 2005. Most of these conditions are opportunistic infections that can be easily treated in healthy people.

Stage I: HIV disease is asymptomatic and not categorized as AIDS
Stage II: include minor mucocutaneous manifestations and recurrent upper respiratory tract infections
Stage III: includes unexplained chronic diarrhea for longer than a month, severe bacterial infections and pulmonary tuberculosis or
Stage IV includes toxoplasmosis of the brain, candidiasis of the esophagus, trachea, bronchi or lungs and Kaposi's sarcoma; these diseases are used as indicators of AIDS.

CDC Classification System for HIV InfectionEdit

Main article: CDC Classification System for HIV Infection

In the USA, the definition of AIDS is governed by the Centers for Disease Control and Prevention (CDC). In 1993, the CDC expanded their definition of AIDS to include healthy HIV positive people with a CD4 positive T cell count of less than 200 per µl of blood. The majority of new AIDS cases in the United States are reported on the basis of a low T cell count in the presence of HIV infection [15]

HIV testEdit

Main article: HIV test

Approximately half of those infected with HIV don't know that they are infected until they are diagnosed with AIDS. HIV test kits are used to screen donor blood and blood products, and to diagnose HIV in individuals. Typical HIV tests, including the HIV enzyme immunoassay and the Western blot assay, detect HIV antibodies in serum, plasma, oral fluid, dried blood spot or urine of patients. Other tests to look for HIV antigens, HIV-RNA, and HIV-DNA are also commercially available and can be used to detect HIV infection prior to the development of detectable antibodies. However, these assays are not specifically approved by the U.S. Food and Drug Administration for the diagnosis of HIV infection.

Symptoms and ComplicationsEdit

Hiv-timecourse

A generalized graph of the relationship between HIV copies (viral load) and CD4 counts over the average course of untreated HIV infection; any particular individuals' disease course may vary considerably.

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 [16]. Nearly every organ system is affected. People with AIDS also have an increased risk of developing various cancers such as Kaposi 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 [17][18]. After the diagnosis of AIDS is made, the current average survival time with antiretroviral therapy is estimated to be between 4 to 5 years [19], but because new treatments continue to be developed and because HIV continues to evolve resistance to treatments, estimates of survival time are likely to continue to change. Without antiretroviral therapy, progression to death normally occurs within a year [7]. Most patients die from opportunistic infections or malignancies associated with the progressive failure of the immune system [20].

The rate of clinical disease progression varies widely between individuals and has been shown to be affected by many factors such as host susceptibility [8][9][21], health care and co-infections [7][20], and peculiarities of the viral strain [13][22][23]. Also, the specific opportunistic infections that AIDS patients develop depends in part on the prevalence of these infections in the geographic area in which the patient lives.

The major pulmonary illnessesEdit

  • Pneumocystis jiroveci pneumonia: Pneumocystis jiroveci pneumonia (originally known as Pneumocystis carinii pneumonia, often abbreviated PCP) is relatively rare in normal, immunocompetent people but common among HIV-infected individuals. Before the advent of effective treatment and diagnosis 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 per µl [24].
  • Tuberculosis: Among infections associated with HIV, tuberculosis (TB) is unique in that it may be transmitted to immunocompetent persons via the respiratory route, is easily treatable once identified, may occur in early-stage HIV disease, and is preventable with drug therapy. However, multi-drug resistance is a potentially serious problem. 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 may present atypically and extrapulmonary TB is common infecting bone marrow, bone, urinary and gastrointestinal tracts, liver, regional lymph nodes, and the central nervous system [25].

The major gastro-intestinal illnessesEdit

  • Unexplained chronic diarrhea: In HIV infection, there are many possible causes of diarrhea, including common bacterial (Salmonella, Shigella, Listeria, Campylobacter, or Escherichia coli) and parasitic infections, and uncommon opportunistic infections such as cryptosporidiosis, microsporidiosis, Mycobacterium avium complex (MAC) and cytomegalovirus (CMV) colitis. Diarrhea may follow a course of antibiotics (common for Clostridium difficile). It may also be a side effect of several drugs used to treat HIV, or it may simply accompany HIV infection, particularly during primary HIV infection. 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 [27].

The major neurological illnessesEdit

  • Toxoplasmosis: Toxoplasmosis is a disease caused by the single-celled parasite called Toxoplasma gondii. T. gondii usually infects the brain causing toxoplasma encephalitis. It can also infect and cause disease in the eyes and lungs [28].
  • Progressive multifocal leukoencephalopathy: Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease, in which the myelin sheath covering the axons of nerve cells is gradually destroyed, impairing 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 severly weakened, as is the case for AIDS patients. It progresses rapidly, usually causing death within months of diagnosis [29].
  • HIV-associated dementia: HIV-1 associated dementia (HAD) is a metabolic encephalopathy induced by HIV infection and fueled by immune activation of brain macrophages and microglia [30]. These cells are actively infected with HIV and secrete neurotoxins of both host and viral origin. Specific neurologic impairments are manifested by cognitive, behavioral, and motor abnormalities that occur after years of HIV infection and is associated with low CD4+ T cell levels and high plasma viral loads. Prevalence is between 10-20% in Western countries [31] and has only been seen in 1-2% of India based infections [32][33].
  • Cryptococcal meningitis This infection of the meninges (the membrane covering the brain and spinal cord) by the fungus Cryptococcus neoformans can cause fevers, headache, fatigue, nausea, and vomiting. Patients may also develop seizures and confusion. If untreated, it can be lethal.

The major HIV-associated malignanciesEdit

Patients with HIV infection have substantially increased incidence of several malignancies [34][35]. Several of these, Kaposi's sarcoma, high-grade lymphoma, and cervical cancer confer a diagnosis of AIDS when they occur in an HIV-infected person.

  • Kaposi's sarcoma: Kaposi's sarcoma is the most common tumor in HIV-infected patients. The appearance of this tumor in young gay men in 1981 was one of the first signals of the AIDS epidemic. It is caused by a gammaherpesvirus called Kaposi's sarcoma-associated herpes virus (KSHV). It often appears as purplish nodules on the skin, but other organs, especially the mouth, gastrointestinal tract, and lungs can be affected.
  • High-grade lymphoma: Several high-grade B cell lymphomas have substantially increased incidence in HIV-infected patients and often portend a poor prognosis. The most common AIDS-defining lymphomas are Burkitt's lymphoma, Burkitt's-like lymphoma, and diffuse large B-cell lymphoma (DLBCL), including primary central nervous system lymphoma. Primary effusion lymphoma is less common. Many of these lymphomas are caused by either Epstein-Barr virus (EBV) or KSHV.
  • Other tumors: In addition to the AIDS-defining tumors listed above, HIV-infected patients are also at increased risk of certain other tumors, such as Hodgkin's disease and anal and rectal carcinomas. However, the incidence of many common tumors, such as breast cancer or colon cancer, are not increased in HIV-infected patients. Most AIDS-associated malignancies are caused by co-infection of patients with an oncogenic DNA virus, especially Epstein-Barr virus (EBV), Kaposi's sarcoma-associated herpesvirus (KSHV), and human papillomavirus (HPV). In areas where HAART is extensively used to treat AIDS, the incidence of many AIDS-related malignancies has decreased, but at the same time malignancies overall have become the most common cause of death of HIV-infected patients [36].

Other opportunistic infectionsEdit

Patients with AIDS and severe immunosuppression often develop opportunistic infections that present with non-specific symptoms, especially low grade fevers and weight loss. These include infection with Mycobacterium avium-intracellulare and cytomegalovirus (CMV). CMV can also 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 [37].

TransmissionEdit

Since the beginning of the epidemic, three main transmission routes of HIV have been identified:

  • Sexual route. The majority of HIV infections have been, and still are, acquired through unprotected sexual relations. Sexual transmission occurs when there is contact between sexual secretions of one partner with the rectal, genital or mouth mucous membranes of another.
  • Blood or blood product route. This transmission route is particularly important for intravenous drug users, hemophiliacs and recipients of blood transfusions and blood products. Health care workers (nurses, laboratory workers, doctors etc) are also concerned, although more rarely. Also concerned by this route are people who give and receive tattoos and piercings.
  • Mother-to-child route (vertical transmission). The transmission of the virus from the mother to the child can occur in utero during the last weeks of pregnancy and at childbirth. Breast feeding also presents a risk of infection for the baby. In the absence of treatment, the transmission rate between the mother and child was 20%. However, where treatment is available, combined with the availability of Cesarian section, this has been reduced to 1%.

HIV has been found in the saliva, tears and urine of infected individuals, but due to the low concentration of virus in these biological liquids, the risk is considered to be negligible.

PreventionEdit

A great deal of effort has gone into the development and evalution of preventative strategies and programs.

Main article: AIDS prevention

TreatmentEdit

Main article: Antiretroviral drug
Further information: HIV vaccine

There is currently no cure for HIV or AIDS. Infection with HIV usually leads to AIDS and ultimately death. However, in western countries, most patients survive many years following diagnosis because of the availability of the highly active antiretroviral therapy (HAART)[19]. In the absence of HAART, progression from HIV infection to AIDS occurs at a median of between nine to ten years and the median survival time after developing AIDS is only 9.2 months[7]. HAART dramatically increases the time from diagnosis to death, and treatment research continues.

Current optimal HAART options consist of combinations (or "cocktails") consisting of at least three drugs belonging to at least two types, or "classes," of anti-retroviral agents. Typical regimens consist of two nucleoside analogue reverse transcriptase inhibitors (NRTIs) plus either a protease inhibitor or a non nucleoside reverse transcriptase inhibitor (NNRTI). This treatment is frequently referred to as HAART (highly-active anti-retroviral therapy) [38]. Anti-retroviral treatments, along with medications intended to prevent AIDS-related opportunistic infections, have played a part in delaying complications associated with AIDS, reducing the symptoms of HIV infection, and extending patients' life spans. Over the past decade the success of these treatments in prolonging and improving the quality of life for people with AIDS has improved dramatically [39][40].

Because HIV disease progression in children is more rapid than in adults, and laboratory parameters are less predictive of risk for disease progression, particularly for young infants, treatment recommendations from the DHHS have been more aggressive in children than in adults, the current guidelines were published November 3 2005 [41].

The DHHS also recommends that doctors should assess the viral load, rapidity in CD4 decline, and patient readiness while deciding when to recommend initiating treatment [42].

There are several concerns about antiretroviral regimens. The drugs can have serious side effects[43]. Regimens can be complicated, requiring patients to take several pills at various times during the day, although treatment regimens have been greatly simplified in recent years. If patients miss doses, drug resistance can develop [44]. Also, anti-retroviral drugs are costly, and the majority of the world's infected individuals do not have access to medications and treatments for HIV and AIDS.

Research to improve current treatments includes decreasing side effects of current drugs, further simplifying drug regimens to improve adherence, and determining the best sequence of regimens to manage drug resistance.

A number of studies have shown that measures to prevent opportunistic infections can be beneficial when treating patients with HIV infection or AIDS. Vaccination against hepatitis A and B is advised for patients who are not infected with these viruses and are at risk of getting infected. In addition, AIDS patients should receive vaccination against Streptococcus pneumoniae and should receive yearly vaccination against influenza virus. Patients with substantial immunosuppression are generally advised to receive prophylactic therapy for Pneumocystis jiroveci pneumonia (PCP), and many patients may benefit from prophylactic therapy for toxoplasmosis and Cryptococcus meningitis.

Alternative medicineEdit

Ever since AIDS entered the public consciousness, various forms of alternative medicine have been used to try to treat symptoms or to try to affect the course of the disease itself. In the first decade of the epidemic when no useful conventional treatment was available, a large number of people with AIDS experimented with alternative therapies. The definition of "alternative therapies" in AIDS has changed since that time. During that time, the phrase often referred to community-driven treatments, not being tested by government or pharmaceutical company research, that some hoped would directly suppress the virus or stimulate immunity against it. These kinds of approaches have become less common over time as AIDS drugs have become more effective.

The phrase then and now also refers to other approaches that people hoped would improve their symptoms or their quality of life--for instance, massage, herbal and flower remedies and acupuncture; when used with conventional treatment, many now refer to these as "complementary" approaches. None of these treatments have been proven in controlled trials to have any effect in treating HIV or AIDS directly. However, some may improve feelings of well-being in people who believe in their value. Additionally, people with AIDS, like people with other illnesses such as cancer, also sometimes use marijuana to treat pain, combat nausea and stimulate appetite.

EpidemiologyEdit

Main article: AIDS pandemic
Africa HIV-AIDS 300px

Map of Africa coloured according to the percentage of the Adult (ages 15-49) population with HIV/AIDS.

UNAIDS and the WHO estimate that AIDS has killed more than 25 million people since it was first recognized in 1981, making it one of the most destructive epidemics in recorded history. Despite recent, improved access to antiretroviral treatment and care in many regions of the world, the AIDS epidemic claimed an estimated 3.1 million (between 2.8 and 3.6 million) lives in 2005 of which more than half a million (570,000) were children [3].

Globally, between 36.7 and 45.3 million people are currently living with HIV [3]. In 2005, between 4.3 and 6.6 million people were newly infected and between 2.8 and 3.6 million people with AIDS died, an increase from 2004 and the highest number since 1981.

Sub-Saharan Africa remains by far the worst-affected region, with an estimated 23.8 to 28.9 million people currently living with HIV. More than 60% of all people living with HIV are in sub-Saharan Africa, as are more than three quarters (76%) of all women living with HIV [3]. South & South East Asia are second most affected with 15%. AIDS accounts for the deaths of 500,000 children.

The latest evaluation report of the World Bank's Operations Evaluation Department assesses the development effectiveness of the World Bank's country-level HIV/AIDS assistance defined as policy dialogue, analytic work, and lending with the explicit objective of reducing the scope or impact of the AIDS epidemic [45]. This is the first comprehensive evaluation of the World Bank's HIV/AIDS support to countries, from the beginning of the epidemic through mid-2004. Because the Bank's assistance is for implementation of government programs by government, it provides important insights on how national AIDS programs can be made more effective.

The development of HAART as effective therapy for HIV infection and AIDS has substantially reduced the death rate from this disease in those areas where it is widely available. This has created the misperception that the disease has gone away. In fact, as the life expectancy of persons with AIDS has increased in countries where HAART is widely used, the number of persons living with AIDS has increased substantially. In the United States, for example, the number of persons with AIDS increased from about 35,000 in 1988 to over 220,000 in 1996 [46].

Origin of HIV/AIDSEdit

Main article: AIDS origin

The official date for the beginning of the AIDS epidemic is marked as June 18, 1981, when the U.S. Center for Disease Control and Prevention reported a cluster of Pneumocystis carinii pneumonia (now classified as Pneumocystis jiroveci pneumonia) in five gay men in Los Angeles [47]. Originally dubbed GRID, or Gay-Related Immune Deficiency, health authorities soon realized that nearly half of the people identified with the syndrome were not gay. In 1982, the CDC introduced the term AIDS to describe the newly recognized syndrome.

Three of the earliest known instances of HIV infection are as follows:

  1. A plasma sample taken in 1959 from an adult male living in what is now the Democratic Republic of Congo [48].
  2. HIV found in tissue samples from an American teenager who died in St. Louis in 1969.
  3. HIV found in tissue samples from a Norwegian sailor who died around 1976.

Two species of HIV infect humans: HIV-1 and HIV-2. HIV-1 is more virulent and more easily transmitted. HIV-1 is the source of the majority of HIV infections throughout the world, while HIV-2 is less easily transmitted and is largely confined to West Africa [49]. Both HIV-1 and HIV-2 are of primate origin. The origin of HIV-1 is the Central Common Chimpanzee (Pan troglodytes troglodytes). The origin of HIV-2 has been established to be the Sooty Mangabey (Cercocebus atys), an Old World monkey of Guinea Bissau, Gabon, and Cameroon.

One currently controversial possibility for the origin of HIV/AIDS was discussed in a 1992 Rolling Stone magazine article by freelance journalist Tom Curtis. He put forward the theory that AIDS was inadvertantly caused in the late 1950's in the Belgian Congo by Hilary Koprowski's research into a polio vaccine [50]. Although subsequently retracted due to libel issues surrounding its claims, the Rolling Stone article motivated another freelance journalist, Edward Hooper, to probe more deeply into this subject. Hooper's research resulted in his publishing a 1999 book, The River, in which he alleged that an experimental oral polio vaccine prepared using chimpanzee kidney tissue was the route through which SIV crossed into humans to become HIV, thus starting the human AIDS pandemic[51].

For more details on this topic, see OPV AIDS hypothesis.

Alternative theoriesEdit

Main article: AIDS reappraisal

A minority of scientists and activists question the connection between HIV and AIDS [52], or the existence of HIV [53], or the validity of current testing methods. These claims are met with resistance by, and often evoke frustration and hostility from, most of the scientific community, who accuse the dissidents of ignoring evidence in favor of HIV's role in AIDS, and irresponsibly posing a dangerous threat to public health by their continued activities [54]. Dissidents assert that the current mainstream approach to AIDS, based on HIV causation, has resulted in inaccurate diagnoses, psychological terror, toxic treatments, and a squandering of public funds. The debate and controversy regarding this issue from the early 1980s to the present has provoked heated emotions and passions from both sides.


JournalsEdit

See alsoEdit

References & BibliographyEdit



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