HIV/AIDS

HIV/AIDS

HIV/AIDS
A red ribbon in the shape of a bow
The red ribbon is a symbol for solidarity with HIV-positive people and those living with AIDS.[1]
Classification and external resources
Specialty Infectious disease
ICD-10 B20 – B24
ICD-9-CM 042-044
OMIM 609423
DiseasesDB 5938
MedlinePlus 000594
eMedicine emerg/253
MeSH D000163

Human immunodeficiency virus infection and acquired immune deficiency syndrome (HIV/AIDS) is a spectrum of conditions caused by infection with the [13] AIDS was first recognized by the United States Centers for Disease Control and Prevention (CDC) in 1981 and its cause—HIV infection—was identified in the early part of the decade.[14] HIV/AIDS has had a great impact on society, both as an illness and as a source of discrimination. The disease also has significant economic impacts. There are many misconceptions about HIV/AIDS such as the belief that it can be transmitted by casual non-sexual contact. The disease has become subject to many controversies involving religion. It has attracted international medical and political attention as well as large-scale funding since it was identified in the 1980s.[15]

Contents

  • Signs and symptoms 1
    • Acute infection 1.1
    • Clinical latency 1.2
    • Acquired immunodeficiency syndrome 1.3
  • Transmission 2
    • Sexual 2.1
    • Body fluids 2.2
    • Mother-to-child 2.3
  • Virology 3
  • Pathophysiology 4
  • Diagnosis 5
    • HIV testing 5.1
    • Classifications 5.2
  • Prevention 6
    • Sexual contact 6.1
    • Pre-exposure 6.2
    • Post-exposure 6.3
    • Mother-to-child 6.4
    • Vaccination 6.5
  • Treatment 7
    • Antiviral therapy 7.1
    • Opportunistic infections 7.2
    • Diet 7.3
    • Alternative medicine 7.4
  • Prognosis 8
  • Epidemiology 9
  • History 10
    • Discovery 10.1
    • Origins 10.2
  • Society and culture 11
    • Stigma 11.1
    • Economic impact 11.2
    • Religion and AIDS 11.3
    • Media portrayal 11.4
    • Criminal transmission 11.5
    • Misconceptions 11.6
  • Research 12
  • References 13
  • Further reading 14
  • External links 15

Signs and symptoms

There are three main stages of HIV infection: acute infection, clinical latency and AIDS.[16][17]

Acute infection

A diagram of a human torso labelled with the most common symptoms of an acute HIV infection
Main symptoms of acute HIV infection

The initial period following the contraction of HIV is called acute HIV, primary HIV or acute retroviral syndrome.[16][18] Many individuals develop an influenza-like illness or a mononucleosis-like illness 2–4 weeks post exposure while others have no significant symptoms.[19][20] Symptoms occur in 40–90% of cases and most commonly include fever, large tender lymph nodes, throat inflammation, a rash, headache, and/or sores of the mouth and genitals.[18][20] The rash, which occurs in 20–50% of cases, presents itself on the trunk and is maculopapular, classically.[21] Some people also develop opportunistic infections at this stage.[18] Gastrointestinal symptoms such as nausea, vomiting or diarrhea may occur, as may neurological symptoms of peripheral neuropathy or Guillain-Barre syndrome.[20] The duration of the symptoms varies, but is usually one or two weeks.[20]

Due to their nonspecific character, these symptoms are not often recognized as signs of HIV infection. Even cases that do get seen by a family doctor or a hospital are often misdiagnosed as one of the many common infectious diseases with overlapping symptoms. Thus, it is recommended that HIV be considered in people presenting an unexplained fever who may have risk factors for the infection.[20]

Clinical latency

The initial symptoms are followed by a stage called clinical latency, asymptomatic HIV, or chronic HIV.[17] Without treatment, this second stage of the natural history of HIV infection can last from about three years[22] to over 20 years[23] (on average, about eight years).[24] While typically there are few or no symptoms at first, near the end of this stage many people experience fever, weight loss, gastrointestinal problems and muscle pains.[17] Between 50 and 70% of people also develop persistent generalized lymphadenopathy, characterized by unexplained, non-painful enlargement of more than one group of lymph nodes (other than in the groin) for over three to six months.[16]

Although most HIV-1 infected individuals have a detectable viral load and in the absence of treatment will eventually progress to AIDS, a small proportion (about 5%) retain high levels of CD4+ T cells (T helper cells) without antiretroviral therapy for more than 5 years.[20][25] These individuals are classified as HIV controllers or long-term nonprogressors (LTNP).[25] Another group consists of those who maintain a low or undetectable viral load without anti-retroviral treatment, known as "elite controllers" or "elite suppressors". They represent approximately 1 in 300 infected persons.[26]

Acquired immunodeficiency syndrome

A diagram of a human torso labelled with the most common symptoms of AIDS
Main symptoms of AIDS.

Acquired immunodeficiency syndrome (AIDS) is defined in terms of either a CD4+ T cell count below 200 cells per µL or the occurrence of specific diseases in association with an HIV infection.[20] In the absence of specific treatment, around half of people infected with HIV develop AIDS within ten years.[20] The most common initial conditions that alert to the presence of AIDS are

  • HIV/AIDS at DMOZ
  • Joint United Nations Program on HIV/AIDS
  • AIDSinfo – HIV/AIDS Treatment Information, U.S. Department of Health and Human Services

External links

  • Mandell, Gerald L.; Bennett, John E.; Dolin, Raphael, eds. (2010). Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases (7th ed.). Philadelphia, PA: Churchill Livingstone/Elsevier.  
  •  

Further reading

  1. ^ "World AIDS Day".  
  2. ^ Sepkowitz KA (June 2001). "AIDS—the first 20 years". N. Engl. J. Med. 344 (23): 1764–72.  
  3. ^ editors, Alexander Krämer, Mirjam Kretzschmar, Klaus Krickeberg, (2010). Modern infectious disease epidemiology concepts, methods, mathematical models, and public health (Online-Ausg. ed.). New York: Springer. p. 88.  
  4. ^ Wilhelm Kirch (2008). Encyclopedia of public health. New York: Springer. pp. 676–677.  
  5. ^ a b c d e f g h i j Markowitz, edited by William N. Rom ; associate editor, Steven B. (2007). Environmental and occupational medicine (4th ed.). Philadelphia: Wolters Kluwer/Lippincott Williams & Wilkins. p. 745.  
  6. ^ "HIV and Its Transmission".  
  7. ^ "Antiretroviral treatment as prevention (TASP) of HIV and TB". who.int. June 2012. Retrieved 4 April 2015. 
  8. ^ a b Guideline on when to start antiretroviral therapy and on pre-exposure prophylaxis for HIV. (PDF). WHO. 2015. p. 13.  
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  10. ^ a b "Fact Sheet". UNAIDS.org. 2013. Retrieved December 4, 2013. 
  11. ^ a b GBD 2013 Mortality and Causes of Death, Collaborators (17 December 2014). "Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013.". Lancet 385 (9963): 117–71.  
  12. ^ a b Kallings LO (2008). "The first postmodern pandemic: 25 years of HIV/AIDS". Journal of Internal Medicine 263 (3): 218–43.  (subscription required)
  13. ^ a b Sharp, PM; Hahn, BH (September 2011). "Origins of HIV and the AIDS Pandemic". Cold Spring Harbor perspectives in medicine 1 (1): a006841.  
  14. ^ Gallo RC (2006). "A reflection on HIV/AIDS research after 25 years". Retrovirology 3 (1): 72.  
  15. ^ Harden, Victoria Angela (2012). AIDS at 30: A History. Potomac Books Inc. p. 324.  
  16. ^ a b c d e f Mandell, Bennett, and Dolan (2010). Chapter 121.
  17. ^ a b c "Stages of HIV". U.S. Department of Health & Human Services. Dec 2010. Retrieved 13 June 2012. 
  18. ^ a b c d e f g h i j k l m n o p WHO case definitions of HIV for surveillance and revised clinical staging and immunological classification of HIV-related disease in adults and children. (PDF). Geneva: World Health Organization. 2007. pp. 6–16.  
  19. ^ Diseases and disorders. Tarrytown, NY: Marshall Cavendish. 2008. p. 25.  
  20. ^ a b c d e f g h i j k l m n Mandell, Bennett, and Dolan (2010). Chapter 118.
  21. ^ a b c d e f g h i j k l m n o p q Vogel, M; Schwarze-Zander, C; Wasmuth, JC; Spengler, U; Sauerbruch, T; Rockstroh, JK (July 2010). "The treatment of patients with HIV". Deutsches Ärzteblatt international 107 (28–29): 507–15; quiz 516.  
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  23. ^ Charles B. Hicks, MD (2001). Jacques W. A. J. Reeders & Philip Charles Goodman, ed. Radiology of AIDS. Berlin [u.a.]: Springer. p. 19.  
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References

Many governments and research institutions participate in HIV/AIDS research. This research includes behavioral health interventions such as sex education, and drug development, such as research into microbicides for sexually transmitted diseases, HIV vaccines, and antiretroviral drugs. Other medical research areas include the topics of pre-exposure prophylaxis, post-exposure prophylaxis, and circumcision and HIV.

HIV/AIDS research includes all medical research which attempts to prevent, treat, or cure HIV/AIDS along with fundamental research about the nature of HIV as an infectious agent and AIDS as the disease caused by HIV.

Research

Several discredited conspiracy theories have held that HIV was created by scientists, either inadvertently or deliberately. Operation INFEKTION was a worldwide Soviet active measures operation to spread the claim that the United States had created HIV/AIDS. Surveys show that a significant number of people believed – and continue to believe – in such claims.[265]

A small group of individuals continue to dispute the connection between HIV and AIDS,[258] the existence of HIV itself, or the validity of HIV testing and treatment methods.[259][260] These claims, known as AIDS denialism, have been examined and rejected by the scientific community.[261] However, they have had a significant political impact, particularly in South Africa, where the government's official embrace of AIDS denialism (1999–2005) was responsible for its ineffective response to that country's AIDS epidemic, and has been blamed for hundreds of thousands of avoidable deaths and HIV infections.[262][263][264]

There are many misconceptions about HIV and AIDS. Three of the most common are that AIDS can spread through casual contact, that sexual intercourse with a virgin will cure AIDS,[252][253][254] and that HIV can infect only gay men and drug users. In 2014, some among the British public wrongly thought you could get HIV from kissing (16%), sharing a glass (5%), spitting (16%), a public toilet seat (4%), and coughing or sneezing (5%).[255] Other misconceptions are that any act of anal intercourse between two uninfected gay men can lead to HIV infection, and that open discussion of HIV and homosexuality in schools will lead to increased rates of AIDS.[256][257]

Misconceptions

Criminal transmission of HIV is the intentional or reckless infection of a person with the human immunodeficiency virus (HIV). Some countries or jurisdictions, including some areas of the United States, have laws that criminalize HIV transmission or exposure.[251] Others may charge the accused under laws enacted before the HIV pandemic.

Criminal transmission

Therese Frare's photograph of gay activist David Kirby, as he lay dying from AIDS while surrounded by family, was taken in April 1990. LIFE magazine said the photo became the one image "most powerfully identified with the HIV/AIDS epidemic." The photo was displayed in LIFE magazine, was the winner of the World Press Photo, and acquired worldwide notoriety after being used in a United Colors of Benetton advertising campaign in 1992.[247] In 1996, Johnson Aziga, a Ugandan-born Canadian was diagnosed with HIV, but subsequently had unprotected sex with 11 women without disclosing his diagnosis. By 2003 seven had contracted HIV, and two died from complications related to AIDS.[248][249] Aziga was convicted of first-degree murder and is liable to a life sentence.[250]

One of the first high-profile cases of AIDS was the American Rock Hudson, a gay actor 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. He had been diagnosed during 1984.[241] A notable British casualty of AIDS that year was Nicholas Eden, a gay politician and son of the late prime minister Anthony Eden.[242] On November 24, 1991, the virus claimed the life of British rock star Freddie Mercury, lead singer of the band Queen, who died from an AIDS-related illness having only revealed the diagnosis on the previous day.[243] However, he had been diagnosed as HIV positive in 1987.[244] One of the first high-profile heterosexual cases of the virus was Arthur Ashe, the American tennis player. He was diagnosed as HIV positive on August 31, 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.[245] He died as a result on February 6, 1993 at age 49.[246]

Media portrayal

Some religious organisations have claimed that prayer can cure HIV/AIDS. In 2011, the BBC reported that some churches in London were claiming that prayer would cure AIDS, and the Hackney-based Centre for the Study of Sexual Health and HIV reported that several people stopped taking their medication, sometimes on the direct advice of their pastor, leading to a number of deaths.[240] The Synagogue Church Of All Nations advertise an "anointing water" to promote God's healing, although the group deny advising people to stop taking medication.[240]

The topic of religion and AIDS has become highly controversial in the past twenty years, primarily because some religious authorities have publicly declared their opposition to the use of condoms.[238][239] The religious approach to prevent the spread of AIDS according to a report by American health expert Matthew Hanley titled The Catholic Church and the Global AIDS Crisis argues that cultural changes are needed including a re-emphasis on fidelity within marriage and sexual abstinence outside of it.[239]

Religion and AIDS

At the household level, AIDS causes both loss of income and increased spending on healthcare. A study in Côte d'Ivoire showed that households having a person with HIV/AIDS spent twice as much on medical expenses as other households. This additional expenditure also leaves less income to spend on education and other personal or family investment.[237]

By affecting mainly young adults, AIDS reduces the taxable population, in turn reducing the resources available for public expenditures such as education and health services not related to AIDS resulting in increasing pressure for the state's finances and slower growth of the economy. This causes a slower growth of the tax base, an effect that is reinforced if there are growing expenditures on treating the sick, training (to replace sick workers), sick pay and caring for AIDS orphans. This is especially true if the sharp increase in adult mortality shifts the responsibility and blame from the family to the government in caring for these orphans.[235]

Returning to work after beginning treatment for HIV/AIDS is difficult, and affected people often work less than the average worker. Unemployment in people with HIV/AIDS also is associated with suicidal ideation, memory problems, and social isolation; employment increases self-esteem, sense of dignity, confidence, and quality of life. A 2015 Cochrane review found low-quality evidence that antiretroviral treatment helps people with HIV/AIDS work more, and increases the chance that a person with HIV/AIDS will be employed.[236]

HIV/AIDS affects the economics of both individuals and countries.[190] The gross domestic product of the most affected countries has decreased due to the lack of human capital.[190][234] Without proper nutrition, health care and medicine, large numbers of people die from AIDS-related complications. They will not only be unable to work, but will also require significant medical care. It is estimated that as of 2007 there were 12 million AIDS orphans.[190] Many are cared for by elderly grandparents.[235]

A graph showing an number of increasing lines followed by a sharp fall of the lines starting in mid-1980s to 1990s
Changes in life expectancy in some African countries, 1960-2012

Economic impact

In 2003, as part of an overall reform of marriage and population legislation, it became legal for people with AIDS to marry in China.[233]

In many developed countries, there is an association between AIDS and homosexuality or bisexuality, and this association is correlated with higher levels of sexual prejudice, such as anti-homosexual/bisexual attitudes.[231] There is also a perceived association between AIDS and all male-male sexual behavior, including sex between uninfected men.[228] However, the dominant mode of spread worldwide for HIV remains heterosexual transmission.[232]

Often, AIDS stigma is expressed in conjunction with one or more other stigmas, particularly those associated with homosexuality, bisexuality, promiscuity, prostitution, and intravenous drug use.[230]

  • Instrumental AIDS stigma—a reflection of the fear and apprehension that are likely to be associated with any deadly and transmissible illness.[228]
  • Symbolic AIDS stigma—the use of HIV/AIDS to express attitudes toward the social groups or lifestyles perceived to be associated with the disease.[228]
  • Courtesy AIDS stigma—stigmatization of people connected to the issue of HIV/AIDS or HIV-positive people.[229]

AIDS stigma has been further divided into the following three categories:

AIDS stigma exists around the world in a variety of ways, including ostracism, rejection, discrimination and avoidance of HIV infected people; compulsory HIV testing without prior consent or protection of confidentiality; violence against HIV infected individuals or people who are perceived to be infected with HIV; and the quarantine of HIV infected individuals.[226] Stigma-related violence or the fear of violence prevents many people from seeking HIV testing, returning for their results, or securing treatment, possibly turning what could be a manageable chronic illness into a death sentence and perpetuating the spread of HIV.[227]

A teenage male with the hand of another resting on his left shoulder smiling for the camera
Ryan White became a poster child for HIV after being expelled from school because he was infected.[225]

Stigma

Society and culture

The earliest well documented case of HIV in a human dates back to 1959 in the Congo.[222] The virus may have been present in the United States as early as 1966,[223] but the vast majority of infections occurring outside sub-Saharan Africa (including the U.S.) can be traced back to a single unknown individual who became infected with HIV in Haiti and then brought the infection to the United States some time around 1969.[224] The epidemic then rapidly spread among high-risk groups (initially, sexually promiscuous men who have sex with men). By 1978, the prevalence of HIV-1 among homosexual male residents of New York and San Francisco was estimated at 5%, suggesting that several thousand individuals in the country had been infected.[224]

An alternative view holds that unsafe medical practices in Africa after World War II, such as unsterile reuse of single use syringes during mass vaccination, antibiotic and anti-malaria treatment campaigns, were the initial vector that allowed the virus to adapt to humans and spread.[217][220][221]

Specific proposed high-risk transmission channels, allowing the virus to adapt to humans and spread throughout the society, depend on the proposed timing of the animal-to-human crossing. Genetic studies of the virus suggest that the most recent common ancestor of the HIV-1 M group dates back to circa 1910.[218] Proponents of this dating link the HIV epidemic with the emergence of colonialism and growth of large colonial African cities, leading to social changes, including a higher degree of sexual promiscuity, the spread of prostitution, and the accompanying high frequency of genital ulcer diseases (such as syphilis) in nascent colonial cities.[219] While transmission rates of HIV during vaginal intercourse are low under regular circumstances, they are increased many fold if one of the partners suffers from a sexually transmitted infection causing genital ulcers. Early 1900s colonial cities were notable due to their high prevalence of prostitution and genital ulcers, to the degree that, as of 1928, as many as 45% of female residents of eastern Kinshasa were thought to have been prostitutes, and, as of 1933, around 15% of all residents of the same city had syphilis.[219]

There is evidence that humans who participate in bushmeat activities, either as hunters or as bushmeat vendors, commonly acquire SIV.[216] However, SIV is a weak virus which is typically suppressed by the human immune system within weeks of infection. It is thought that several transmissions of the virus from individual to individual in quick succession are necessary to allow it enough time to mutate into HIV.[217] Furthermore, due to its relatively low person-to-person transmission rate, SIV can only spread throughout the population in the presence of one or more high-risk transmission channels, which are thought to have been absent in Africa before the 20th century.

Both HIV-1 and HIV-2 are believed to have originated in non-human [13] HIV-1 appears to have originated in southern Cameroon through the evolution of SIV(cpz), a simian immunodeficiency virus (SIV) that infects wild chimpanzees (HIV-1 descends from the SIVcpz endemic in the chimpanzee subspecies Pan troglodytes troglodytes).[212][213] The closest relative of HIV-2 is SIV(smm), a virus of the sooty mangabey (Cercocebus atys atys), an Old World monkey living in coastal West Africa (from southern Senegal to western Côte d'Ivoire).[79] New World monkeys such as the owl monkey are resistant to HIV-1 infection, possibly because of a genomic fusion of two viral resistance genes.[214] HIV-1 is thought to have jumped the species barrier on at least three separate occasions, giving rise to the three groups of the virus, M, N, and O.[215]

Left to right: the African green monkey source of SIV, the sooty mangabey source of HIV-2 and the chimpanzee source of HIV-1

Origins

In 1983, two separate research groups led by Robert Gallo and Luc Montagnier independently declared that a novel retrovirus may have been infecting people with AIDS, and published their findings in the same issue of the journal Science.[209][210] Gallo claimed that a virus his group had isolated from a person with AIDS was strikingly similar in shape to other human T-lymphotropic viruses (HTLVs) his group had been the first to isolate. Gallo's group called their newly isolated virus HTLV-III. At the same time, Montagnier's group isolated a virus from a person presenting with swelling of the lymph nodes of the neck and physical weakness, two characteristic symptoms of AIDS. Contradicting the report from Gallo's group, Montagnier and his colleagues showed that core proteins of this virus were immunologically different from those of HTLV-I. Montagnier's group named their isolated virus lymphadenopathy-associated virus (LAV).[200] As these two viruses turned out to be the same, in 1986, LAV and HTLV-III were renamed HIV.[211]

In the early days, 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.[201][202] They also used Kaposi's sarcoma and opportunistic infections, the name by which a task force had been set up in 1981.[203] At one point, the CDC coined the phrase "the 4H disease", since the syndrome seemed to affect homosexuals, heroin users, hemophiliacs, and Haitians.[204][205] In the general press, the term "GRID", which stood for gay-related immune deficiency, had been coined.[206] However, after determining that AIDS was not isolated to the gay community,[203] it was realized that the term GRID was misleading and the term AIDS was introduced at a meeting in July 1982.[207] By September 1982 the CDC started referring to the disease as AIDS.[208]

AIDS was first clinically observed in 1981 in the United States.[29] The initial cases were a cluster of injecting drug users and homosexual men with no known cause of impaired immunity who showed symptoms of Pneumocystis carinii pneumonia (PCP), a rare opportunistic infection that was known to occur in people with very compromised immune systems.[197] Soon thereafter, an unexpected number of homosexual men developed a previously rare skin cancer called Kaposi's sarcoma (KS).[198][199] Many more cases of PCP and KS emerged, alerting U.S. Centers for Disease Control and Prevention (CDC) and a CDC task force was formed to monitor the outbreak.[200]

The Morbidity and Mortality Weekly Report reported in 1981 on what was later to be called "AIDS".

Discovery

History

In 2008 in the United States approximately 1.2 million people were living with HIV, resulting in about 17,500 deaths. The US Centers for Disease Control and Prevention estimated that in 2008 20% of infected Americans were unaware of their infection.[192] In the United Kingdom as of 2009 there where approximately 86,500 cases which resulted in 516 deaths.[193] In Canada as of 2008 there were about 65,000 cases causing 53 deaths.[194] Between the first recognition of AIDS in 1981 and 2009 it has led to nearly 30 million deaths.[195] Prevalence is lowest in Middle East and North Africa at 0.1% or less, East Asia at 0.1% and Western and Central Europe at 0.2%.[189] The worst affected European countries, in 2009 and 2012 estimates, are Russia, Ukraine, Latvia, Moldova, Portugal and Belarus, in order of prevalence.[196]

South & South East Asia is the second most affected; in 2010 this region contained an estimated 4 million cases or 12% of all people living with HIV resulting in approximately 250,000 deaths.[189] Approximately 2.4 million of these cases are in India.[188]

Sub-Saharan Africa is the region most affected. In 2010, an estimated 68% (22.9 million) of all HIV cases and 66% of all deaths (1.2 million) occurred in this region.[188] This means that about 5% of the adult population is infected[189] and it is believed to be the cause of 10% of all deaths in children.[190] Here in contrast to other regions women compose nearly 60% of cases.[188] South Africa has the largest population of people with HIV of any country in the world at 5.9 million.[188] Life expectancy has fallen in the worst-affected countries due to HIV/AIDS; for example, in 2006 it was estimated that it had dropped from 65 to 35 years in Botswana.[12] Mother-to-child transmission, as of 2013, in Botswana and South Africa has decreased to less than 5% with improvement in many other African nations due to improved access to antiretroviral therapy.[191]

HIV/AIDS is a global pandemic.[186] As of 2012, approximately 35.3 million people have HIV worldwide with the number of new infections that year being about 2.3 million.[187] This is down from 3.1 million new infections in 2001.[187] Of these approximately 16.8 million are women and 3.4 million are less than 15 years old.[133] It resulted in about 1.34 million deaths in 2013,[11] down from a peak of 2.2 million in 2005.[133][187]

 A map of the world where most of the land is colored green or yellow except for sub Saharan Africa which is colored red
Estimated prevalence in % of HIV among young adults (15–49) per country as of 2011.[185]
  No data
  <0.10
  0.10–0.5
  0.5–1
  1–5
  5–15
  15–50

Epidemiology

Even with anti-retroviral treatment, over the long term HIV-infected people may experience neurocognitive disorders,[179] osteoporosis,[180] neuropathy,[181] cancers,[182][183] nephropathy,[184] and cardiovascular disease.[145] Some conditions like lipodystrophy may be caused both by HIV and its treatment.[145]

Tuberculosis co-infection is one of the leading causes of sickness and death in those with HIV/AIDS being present in a third of all HIV infected people and causing 25% of HIV related deaths.[176] HIV is also one of the most important risk factors for tuberculosis.[177] Hepatitis C is another very common co-infection where each disease increases the progression of the other.[178] The two most common cancers associated with HIV/AIDS are Kaposi's sarcoma and AIDS-related non-Hodgkin's lymphoma.[171]

The primary causes of death from HIV/AIDS are [166][173] and the particular strain (or strains) of the virus involved.[174][175]

HIV/AIDS has become a [166][167] HAART and appropriate prevention of opportunistic infections reduces the death rate by 80%, and raises the life expectancy for a newly diagnosed young adult to 20–50 years.[165][168][169] This is between two thirds[168] and nearly that of the general population.[21][170] If treatment is started late in the infection, prognosis is not as good:[21] for example, if treatment is begun following the diagnosis of AIDS, life expectancy is ~10–40 years.[21][165] Half of infants born with HIV die before two years of age without treatment.[151]

Disability-adjusted life year for HIV and AIDS per 100,000 inhabitants as of 2004.
  no data
  ≤ 10
  10–25
  25–50
  50–100
  100–500
  500–1000
  1000–2500
  2500–5000
  5000–7500
  7500-10000
  10000-50000
  ≥ 50000

Prognosis

In the US, approximately 60% of people with HIV use various forms of complementary or alternative medicine,[161] even though the effectiveness of most of these therapies has not been established.[162] There is not enough evidence to support the use of herbal medicines.[163] There is insufficient evidence to recommend or support the use of medical cannabis to try to increase appetite or weight gain.[164]

Alternative medicine

[160][159][158][155], and iron can produce adverse effects in HIV positive adults, and is not recommended unless there is documented deficiency.zinc levels by HIV-infected adults is recommended by the WHO; higher intake of vitamin A, RDA Dietary intake of micronutrients at [156] supplementation has improved outcomes for both mothers and children.multivitamin In Africa in nutritionally compromised pregnant and lactating women a [156] supplementation in children reduces mortality and improves growth.vitamin A There is some evidence that [157] is mixed with some tentative evidence of benefit.selenium Evidence for supplementation with [156] supplements.micronutrient A generally healthy diet is promoted. Some evidence has shown a benefit from [155] The

Diet

Measures to prevent opportunistic infections are effective in many people with HIV/AIDS. In addition to improving current disease, treatment with antiretrovirals reduces the risk of developing additional opportunistic infections.[144] Adults and adolescents who are living with HIV (even on anti-retroviral therapy) with no evidence of active tuberculosis in settings with high tuberculosis burden should receive isoniazid preventive therapy (IPT), the tuberculin skin test can be used to help decide if IPT is needed.[149] Vaccination against hepatitis A and B is advised for all people at risk of HIV before they become infected; however it may also be given after infection.[150] Trimethoprim/sulfamethoxazole prophylaxis between four and six weeks of age and ceasing breastfeeding in infants born to HIV positive mothers is recommended in resource limited settings.[151] It is also recommended to prevent PCP when a person's CD4 count is below 200 cells/uL and in those who have or have previously had PCP.[152] People with substantial immunosuppression are also advised to receive prophylactic therapy for toxoplasmosis and Cryptococcus meningitis.[153] Appropriate preventive measures have reduced the rate of these infections by 50% between 1992 and 1997.[154]

Opportunistic infections

[148] The United States guidelines recommend treating all children less than 12 months of age and all those with HIV RNA counts greater than 100,000 copies/mL between one year and five years of age.[147] Current HAART options are combinations (or "cocktails") consisting of at least three medications belonging to at least two types, or "classes," of

A white prescription bottle with the label Stribild. Next to it are ten green oblong pills with the marking 1 on one side and GSI on the other.
Stribild - a common once-daily ART regime consisting of elvitegravir, emtricitabine, tenofovir and the booster cobicistat

Antiviral therapy

There is currently no cure or effective HIV vaccine. Treatment consists of highly active antiretroviral therapy (HAART) which slows progression of the disease.[132] As of 2010 more than 6.6 million people were taking them in low and middle income countries.[133] Treatment also includes preventive and active treatment of opportunistic infections.

Treatment

Currently, there is no licensed vaccine for HIV or AIDS.[128] The most effective vaccine trial to date, RV 144, was published in 2009 and found a partial reduction in the risk of transmission of roughly 30%, stimulating some hope in the research community of developing a truly effective vaccine.[129] Further trials of the RV 144 vaccine are ongoing.[130][131]

Vaccination

Programs to prevent the vertical transmission of HIV (from mothers to children) can reduce rates of transmission by 92–99%.[63][118] This primarily involves the use of a combination of antiviral medications during pregnancy and after birth in the infant and potentially includes bottle feeding rather than breastfeeding.[63][124] If replacement feeding is acceptable, feasible, affordable, sustainable, and safe, mothers should avoid breastfeeding their infants; however exclusive breastfeeding is recommended during the first months of life if this is not the case.[125] If exclusive breastfeeding is carried out, the provision of extended antiretroviral prophylaxis to the infant decreases the risk of transmission.[126] In 2015, Cuba became the first country in the world to eradicate mother-to-child transmission of HIV.[127]

Mother-to-child

PEP treatment is recommended after a sexual assault when the perpetrator is known to be HIV positive, but is controversial when their HIV status is unknown.[122] The duration of treatment is usually four weeks[123] and is frequently associated with adverse effects—where zidovudine is used, about 70% of cases result in adverse effects such as nausea (24%), fatigue (22%), emotional distress (13%) and headaches (9%).[36]

A course of antiretrovirals administered within 48 to 72 hours after exposure to HIV-positive blood or genital secretions is referred to as post-exposure prophylaxis (PEP).[120] The use of the single agent zidovudine reduces the risk of a HIV infection five-fold following a needle-stick injury.[120] As of 2013, the prevention regimen recommended in the United States consists of three medications—tenofovir, emtricitabine and raltegravir—as this may reduce the risk further.[121]

Post-exposure

Universal precautions within the health care environment are believed to be effective in decreasing the risk of HIV.[117] Intravenous drug use is an important risk factor and harm reduction strategies such as needle-exchange programmes and opioid substitution therapy appear effective in decreasing this risk.[118][119]

Antiretroviral treatment among people with HIV whose CD4 count ≤ 550 cells/µL is a very effective way to prevent HIV infection of their partner (a strategy known as treatment as prevention, or TASP).[114] TASP is associated with a 10 to 20 fold reduction in transmission risk.[115][114] Pre-exposure prophylaxis (PrEP) with a daily dose of the medications tenofovir, with or without emtricitabine, is effective in a number of groups including men who have sex with men, couples where one is HIV positive, and young heterosexuals in Africa.[98] It may also be effective in intravenous drug users with a study finding a decrease in risk of 0.7 to 0.4 per 100 person years.[116]

Pre-exposure

[49] It is not known whether treating other sexually transmitted infections is effective in preventing HIV.[113] Voluntary counseling and testing people for HIV does not affect risky behavior in those who test negative but does increase condom use in those who test positive.[112] A substantial minority of young people continues to engage in high-risk practices despite knowing about HIV/AIDS, underestimating their own risk of becoming infected with HIV.[111] provided at school may decrease high risk behavior.Comprehensive sexual education [110] is equally poor.peer education Evidence of any benefit from [109] do not appear to affect subsequent HIV risk.sexual abstinence Programs encouraging [108] Some experts fear that a lower perception of vulnerability among circumcised men may cause more sexual risk-taking behavior, thus negating its preventive effects.[107] The International Antiviral Society, however, does recommend for all sexually active heterosexual males and that it be discussed as an option with men who have sex with men.[106][105][104] is undetermined.men who have sex with men and among developed countries and whether it is of benefit in [103][102] Whether it protects against male-to-female transmission is disputed[101] Consistent

Sexual contact

A run down a two-story building with a number of signs related to AIDS prevention
AIDS Clinic, McLeod Ganj, Himachal Pradesh, India, 2010

Prevention

For surveillance purposes, the AIDS diagnosis still stands even if, after treatment, the CD4+ T cell count rises to above 200 per µL of blood or other AIDS-defining illnesses are cured.[16]

  • Stage 0: the time between a negative or indeterminate HIV test followed less than 180 days by a positive test
  • Stage 1: CD4 count ≥ 500 cells/µl and no AIDS defining conditions
  • Stage 2: CD4 count 200 to 500 cells/µl and no AIDS defining conditions
  • Stage 3: CD4 count ≤ 200 cells/µl or AIDS defining conditions
  • Unknown: if insufficient information is available to make any of the above classifications

The United States Center for Disease Control and Prevention also created a classification system for HIV, and updated it in 2008 and 2014.[93][94] This system classifies HIV infections based on CD4 count and clinical symptoms, and describes the infection in five groups.[94] In those greater than six years of age it is:[94]

  • Primary HIV infection: May be either asymptomatic or associated with acute retroviral syndrome.[18]
  • Stage I: HIV infection is asymptomatic with a CD4+ T cell count (also known as CD4 count) greater than 500 per microlitre (µl or cubic mm) of blood.[18] May include generalized lymph node enlargement.[18]
  • Stage II: Mild symptoms which may include minor mucocutaneous manifestations and recurrent upper respiratory tract infections. A CD4 count of less than 500/µl.[18]
  • Stage III: Advanced symptoms which may include unexplained chronic diarrhea for longer than a month, severe bacterial infections including tuberculosis of the lung, and a CD4 count of less than 350/µl.[18]
  • Stage IV or AIDS: severe symptoms which include toxoplasmosis of the brain, candidiasis of the esophagus, trachea, bronchi or lungs and Kaposi's sarcoma. A CD4 count of less than 200/µl.[18]

The World Health Organization first proposed a definition for AIDS in 1986.[18] Since then, the WHO classification has been updated and expanded several times, with the most recent version being published in 2007.[18] The WHO system uses the following categories:

Two main clinical staging systems are used to classify HIV and HIV-related disease for WHO's staging system does not require laboratory tests, it is suited to the resource-restricted conditions encountered in developing countries, where it can also be used to help guide clinical management. Despite their differences, the two systems allow comparison for statistical purposes.[16][18][93]

Classifications

Antibody tests in children younger than 18 months are typically inaccurate due to the continued presence of maternal antibodies.[91] Thus HIV infection can only be diagnosed by PCR testing for HIV RNA or DNA, or via testing for the p24 antigen.[18] Much of the world lacks access to reliable PCR testing and many places simply wait until either symptoms develop or the child is old enough for accurate antibody testing.[91] In sub-Saharan Africa as of 2007–2009 between 30 and 70% of the population was aware of their HIV status.[92] In 2009, between 3.6 and 42% of men and women in Sub-Saharan countries were tested[92] which represented a significant increase compared to previous years.[92]

Most people infected with HIV develop specific antibodies (i.e. seroconvert) within three to twelve weeks of the initial infection.[20] Diagnosis of primary HIV before seroconversion is done by measuring HIV-RNA or p24 antigen.[20] Positive results obtained by antibody or PCR testing are confirmed either by a different antibody or by PCR.[18]

HIV testing

HIV/AIDS is diagnosed via laboratory testing and then staged based on the presence of certain signs or symptoms.[18] HIV screening is recommended by the United States Preventive Services Task Force for all people 15 years to 65 years of age including all pregnant women.[90] Additionally, testing is recommended for those at high risk, which includes anyone diagnosed with a sexually transmitted illness.[21] In many areas of the world, a third of HIV carriers only discover they are infected at an advanced stage of the disease, when AIDS or severe immunodeficiency has become apparent.[21]

A graph with two lines. One in blue moves from high on the right to low on the left with a brief rise in the middle. The second line in red moves from zero to very high, then drops to low and gradually rises to high again
A generalized graph of the relationship between HIV copies (viral load) and CD4+ T cell counts over the average course of untreated HIV infection.
  CD4+ T Lymphocyte count (cells/mm³)
  HIV RNA copies per mL of plasma

Diagnosis

HIV seeks out and destroys CCR5 expressing CD4+ T cells during acute infection.[87] A vigorous immune response eventually controls the infection and initiates the clinically latent phase. CD4+ T cells in mucosal tissues remain particularly affected.[87] Continuous HIV replication causes a state of generalized immune activation persisting throughout the chronic phase.[88] Immune activation, which is reflected by the increased activation state of immune cells and release of pro-inflammatory cytokines, results from the activity of several HIV gene products and the immune response to ongoing HIV replication. It is also linked to the breakdown of the immune surveillance system of the gastrointestinal mucosal barrier caused by the depletion of mucosal CD4+ T cells during the acute phase of disease.[89]

Although the symptoms of immune deficiency characteristic of AIDS do not appear for years after a person is infected, the bulk of CD4+ T cell loss occurs during the first weeks of infection, especially in the intestinal mucosa, which harbors the majority of the lymphocytes found in the body.[84] The reason for the preferential loss of mucosal CD4+ T cells is that the majority of mucosal CD4+ T cells express the CCR5 protein which HIV uses as a co-receptor to gain access to the cells, whereas only a small fraction of CD4+ T cells in the bloodstream do so.[85] A specific genetic change that alters the CCR5 protein when present in both chromosomes very effectively prevents HIV-1 infection.[86]

Ultimately, HIV causes AIDS by depleting CD4+ T cells. This weakens the immune system and allows opportunistic infections. T cells are essential to the immune response and without them, the body cannot fight infections or kill cancerous cells. The mechanism of CD4+ T cell depletion differs in the acute and chronic phases.[82] During the acute phase, HIV-induced cell lysis and killing of infected cells by cytotoxic T cells accounts for CD4+ T cell depletion, although apoptosis may also be a factor. During the chronic phase, the consequences of generalized immune activation coupled with the gradual loss of the ability of the immune system to generate new T cells appear to account for the slow decline in CD4+ T cell numbers.[83]

After the virus enters the body there is a period of rapid viral replication, leading to an abundance of virus in the peripheral blood. During primary infection, the level of HIV may reach several million virus particles per milliliter of blood.[80] This response is accompanied by a marked drop in the number of circulating CD4+ T cells. The acute viremia is almost invariably associated with activation of CD8+ T cells, which kill HIV-infected cells, and subsequently with antibody production, or seroconversion. The CD8+ T cell response is thought to be important in controlling virus levels, which peak and then decline, as the CD4+ T cell counts recover. A good CD8+ T cell response has been linked to slower disease progression and a better prognosis, though it does not eliminate the virus.[81]

HIV/AIDS explained in a simple way

Pathophysiology

Two types of HIV have been characterized: HIV-1 and HIV-2. HIV-1 is the virus that was originally discovered (and initially referred to also as LAV or HTLV-III). It is more virulent, more infective,[78] and is the cause of the majority of HIV infections globally. The lower infectivity of HIV-2 as compared with HIV-1 implies that fewer people exposed to HIV-2 will be infected per exposure. Because of its relatively poor capacity for transmission, HIV-2 is largely confined to West Africa.[79]

HIV is now known to spread between CD4+ T cells by two parallel routes: cell-free spread and cell-to-cell spread, i.e. it employs hybrid spreading mechanisms.[74] In the cell-free spread, virus particles bud from an infected T cell, enter the blood/extracellular fluid and then infect another T cell following a chance encounter.[74] HIV can also disseminate by direct transmission from one cell to another by a process of cell-to-cell spread.[75][76] The hybrid spreading mechanisms of HIV contribute to the virus's ongoing replication against antiretroviral therapies.[74][77]

HIV is a member of the genus Lentivirus,[68] part of the family Retroviridae.[69] Lentiviruses share many morphological and biological characteristics. Many species of mammals are infected by lentiviruses, which are characteristically responsible for long-duration illnesses with a long incubation period.[70] Lentiviruses are transmitted as single-stranded, positive-sense, enveloped RNA viruses. Upon entry into the target cell, the viral RNA genome is converted (reverse transcribed) into double-stranded DNA by a virally encoded reverse transcriptase that is transported along with the viral genome in the virus particle. The resulting viral DNA is then imported into the cell nucleus and integrated into the cellular DNA by a virally encoded integrase and host co-factors.[71] Once integrated, the virus may become latent, allowing the virus and its host cell to avoid detection by the immune system.[72] Alternatively, the virus may be transcribed, producing new RNA genomes and viral proteins that are packaged and released from the cell as new virus particles that begin the replication cycle anew.[73]

HIV is the cause of the spectrum of disease known as HIV/AIDS. HIV is a retrovirus that primarily infects components of the human immune system such as CD4+ T cells, macrophages and dendritic cells. It directly and indirectly destroys CD4+ T cells.[67]

A large round blue object with a smaller red object attached to it. Multiple small green spots are speckled over both.
Scanning electron micrograph of HIV-1, colored green, budding from a cultured lymphocyte.

Diagram of a HIV virion structure

Virology

HIV can be transmitted from mother to child during pregnancy, during delivery, or through breast milk.[63][64] This is the third most common way in which HIV is transmitted globally.[5] In the absence of treatment, the risk of transmission before or during birth is around 20% and in those who also breastfeed 35%.[63] As of 2008, vertical transmission accounted for about 90% of cases of HIV in children.[63] With appropriate treatment the risk of mother-to-child infection can be reduced to about 1%.[63] Preventive treatment involves the mother taking antiretrovirals during pregnancy and delivery, an elective caesarean section, avoiding breastfeeding, and administering antiretroviral drugs to the newborn.[65] Antiretrovirals when taken by either the mother or the infant decrease the risk of transmission in those who do breastfeed.[66] Many of these measures are however not available in the developing world.[65] If blood contaminates food during pre-chewing it may pose a risk of transmission.[61]

Mother-to-child

People giving or receiving tattoos, piercings, and scarification are theoretically at risk of infection but no confirmed cases have been documented.[61] It is not possible for mosquitoes or other insects to transmit HIV.[62]

[60] Significant risks are also associated with invasive procedures, assisted delivery, and dental care in this area of the world.[60] Blood-borne transmission can be through needle-sharing during intravenous drug use, needle stick injury, transfusion of contaminated blood or blood product, or medical injections with unsterilised equipment. The risk from sharing a needle during [5] The second most frequent mode of HIV transmission is via blood and blood products.

 A black-and-white poster of a young black man with a towel in his left hand with the words
CDC poster from 1989 highlighting the threat of AIDS associated with drug use

Body fluids

Commercial sex workers (including those in pornography) have an increased rate of HIV.[51][52] Rough sex can be a factor associated with an increased risk of transmission.[53] Sexual assault is also believed to carry an increased risk of HIV transmission as condoms are rarely worn, physical trauma to the vagina or rectum is likely, and there may be a greater risk of concurrent sexually transmitted infections.[54]

The viral load of an infected person is an important risk factor in both sexual and mother-to-child transmission.[50] During the first 2.5 months of an HIV infection a person's infectiousness is twelve times higher due to this high viral load.[48] If the person is in the late stages of infection, rates of transmission are approximately eightfold greater.[43]

The most frequent mode of transmission of HIV is through sexual contact with an infected person.[5] The majority of all transmissions worldwide occur through heterosexual contacts (i.e. sexual contacts between people of the opposite sex);[5] however, the pattern of transmission varies significantly among countries. In the United States, as of 2009, most sexual transmission occurred in men who had sex with men,[5] with this population accounting for 64% of all new cases.[42] With regard to unprotected heterosexual contacts, estimates of the risk of HIV transmission per sexual act appear to be four to ten times higher in low-income countries than in high-income countries.[43] In low-income countries, the risk of female-to-male transmission is estimated as 0.38% per act, and of male-to-female transmission as 0.30% per act; the equivalent estimates for high-income countries are 0.04% per act for female-to-male transmission, and 0.08% per act for male-to-female transmission.[43] The risk of transmission from anal intercourse is especially high, estimated as 1.4–1.7% per act in both heterosexual and homosexual contacts.[43][44] While the risk of transmission from oral sex is relatively low, it is still present.[45] The risk from receiving oral sex has been described as "nearly nil";[46] however, a few cases have been reported.[47] The per-act risk is estimated at 0–0.04% for receptive oral intercourse.[48] In settings involving prostitution in low income countries, risk of female-to-male transmission has been estimated as 2.4% per act and male-to-female transmission as 0.05% per act.[43] Risk of transmission increases in the presence of many sexually transmitted infections[49] and genital ulcers.[43] Genital ulcers appear to increase the risk approximately fivefold.[43] Other sexually transmitted infections, such as gonorrhea, chlamydia, trichomoniasis, and bacterial vaginosis, are associated with somewhat smaller increases in risk of transmission.[48]

Sexual

HIV is transmitted by three main routes: sexual contact, exposure to infected body fluids or tissues, and from mother to child during pregnancy, delivery, or breastfeeding (known as vertical transmission).[5] There is no risk of acquiring HIV if exposed to feces, nasal secretions, saliva, sputum, sweat, tears, urine, or vomit unless these are contaminated with blood.[36] It is possible to be co-infected by more than one strain of HIV—a condition known as HIV superinfection.[41]

Average per act risk of getting HIV
by exposure route to an infected source
Exposure route Chance of infection
Blood transfusion 90% [34]
Childbirth (to child) 25%[35]
Needle-sharing injection drug use 0.67%[34]
Percutaneous needle stick 0.30%[36]
Receptive anal intercourse* 0.04–3.0%[37]
Insertive anal intercourse* 0.03%[38]
Receptive penile-vaginal intercourse* 0.05–0.30%[37][39]
Insertive penile-vaginal intercourse* 0.01–0.38% [37][39]
Receptive oral intercourse 0–0.04% [37]
Insertive oral intercourse 0–0.005%[40]
* assuming no condom use
§ source refers to oral intercourse
performed on a man

Transmission

[33] They can also be affected by diverse psychiatric and neurological symptoms independent of opportunistic infections and cancers.[32] Diarrhea is another common symptom present in about 90% of people with AIDS.[31].unintended weight loss (particularly at night), swollen lymph nodes, chills, weakness, and sweats Additionally, people with AIDS frequently have systemic symptoms such as prolonged fevers, [30] (of the layer which lines the inner part of eyelids and the white part of the eye) is more common in those with HIV.Conjunctival cancer [29] (HPV).human papillomavirus Cervical cancer occurs more frequently in those with AIDS due to its association with [29].human herpesvirus 8 Both these cancers are associated with [29] The second most common cancer is lymphoma which is the cause of death of nearly 16% of people with AIDS and is the initial sign of AIDS in 3 to 4%.[29] Kaposi's sarcoma is the most common cancer occurring in 10 to 20% of people with HIV.[21].cervical cancer and primary central nervous system lymphoma, Burkitt's lymphoma, Kaposi's sarcoma People with AIDS have an increased risk of developing various viral induced cancers including [28]