AIDS

AIDS

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The human immunodeficiency virus (HIV) is transmitted through blood and body fluids and gradually breaks down the immune system – usually over a three- to ten-year period – leading to acquired immunodeficiency syndrome, or AIDS. As the virus progresses, people begin to suffer from opportunistic infections. The most common opportunistic infection that leads to death is tuberculosis. A simple blood test can confirm HIV status, but many people live for years without symptoms and may not know they have been infected with HIV. Combinations of drugs known as antiretrovirals (ARVs) help combat the virus, and enable people to live longer, healthier lives without their immune systems deteriorating rapidly. ARVs also significantly reduce the likelihood of the virus being transmitted. As well as treatment, MSF’s comprehensive HIV/AIDS programmes generally include education and awareness activities, condom distribution, HIV testing, counselling and prevention of mother-to-child transmission (PMTCT) services. PMTCT involves the administration of ARV treatment to the mother during pregnancy and labour, and to the infant just after birth.

Human immunodeficiency virus infection / acquired immunodeficiency syndrome (HIV/AIDS) is a disease of the human immune system caused by infection with human immunodeficiency virus (HIV).[1] During the initial infection, a person may experience a brief period of influenza-like illness. This is typically followed by a prolonged period without symptoms. As the illness progresses, it interferes more and more with the immune system, making the person much more likely to get infections, including opportunistic infections and tumors that do not usually affect people who have working immune systems.

HIV is transmitted primarily via unprotected sexual intercourse (including anal and even oral sex), contaminated blood transfusions, hypodermic needles, and from mother to child during pregnancy, delivery, or breastfeeding. Some bodily fluids, such as saliva and tears, do not transmit HIV. Prevention of HIV infection, primarily through safe sex and needle-exchange programs, is a key strategy to control the spread of the disease. There is no cure or vaccine; however, antiretroviral treatment can slow the course of the disease and may lead to a near-normal life expectancy. While antiretroviral treatment reduces the risk of death and complications from the disease, these medications are expensive and may be associated with side effects.

Genetic research indicates that HIV originated in west-central Africa during the early twentieth century. AIDS was first recognized by the Centers for Disease Control and Prevention (CDC) in 1981 and its cause—HIV infection—was identified in the early part of the decade. Since its discovery, AIDS has caused an estimated 36 million deaths (as of 2012). As of 2012, approximately 35.3 million people are living with HIV globally. AIDS is considered a pandemic—a disease outbreak which is present over a large area and is actively spreading.

 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 also 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.

Acute infection

The initial period following the contraction of HIV is called acute HIV, primary HIV or acute retroviral syndrome. Many individuals develop an influenza-like illness or a mononucleosis-like illness 2–4 weeks post exposure while others have no significant symptoms.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. The rash, which occurs in 20–50% of cases, presents itself on the trunk and is maculopapular, classically. Some people also develop opportunistic infections at this stage. Gastrointestinal symptoms such as nausea, vomiting or diarrhea may occur, as may neurological symptoms of peripheral neuropathy or Guillain-Barre syndrome.The duration of the symptoms varies, but is usually one or two weeks.

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 patients presenting an unexplained fever who may have risk factors for the infection.

Clinical latency

The initial symptoms are followed by a stage called clinical latency, asymptomatic HIV, or chronic HIV. Without treatment, this second stage of the natural history of HIV infection can last from about three years to over 20 years(on average, about eight years). 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. 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.

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.These individuals are classified as HIV controllers or long-term nonprogressors (LTNP). Another group is those who also maintain a low or undetectable viral load without anti-retroviral treatment who are known as "elite controllers" or "elite suppressors". They represent approximately 1 in 300 infected persons.

Acquired immunodeficiency syndrome

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.In the absence of specific treatment, around half of people infected with HIV develop AIDS within ten years. The most common initial conditions that alert to the presence of AIDS are pneumocystis pneumonia (40%), cachexia in the form of HIV wasting syndrome (20%) and esophageal candidiasis. Other common signs include recurring respiratory tract infections.

Opportunistic infections may be caused by bacteria, viruses, fungi and parasites that are normally controlled by the immune system. Which infections occur partly depends on what organisms are common in the person's environment. These infections may affect nearly every organ system.

People with AIDS have an increased risk of developing various viral induced cancers including Kaposi's sarcoma, Burkitt's lymphoma, primary central nervous system lymphoma, and cervical cancer. Kaposi's sarcoma is the most common cancer occurring in 10 to 20% of people with HIV. 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%.Both these cancers are associated with human herpesvirus 8.Cervical cancer occurs more frequently in those with AIDS due to its association with human papillomavirus (HPV).

Additionally, people with AIDS frequently have systemic symptoms such as prolonged fevers, sweats (particularly at night), swollen lymph nodes, chills, weakness, and weight loss. Diarrhea is another common symptom present in about 90% of people with AIDS.They can also be affected by diverse psychiatric and neurological symptoms independent of opportunistic infections and cancers.

Transmission

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).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.It is possible to be co-infected by more than one strain of HIV—a condition known as HIV superinfection.

Sexual

The most frequent mode of transmission of HIV is through sexual contact with an infected person. The majority of all transmissions worldwide occur through heterosexual contacts (i.e. sexual contacts between people of the opposite sex); 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, with this population accounting for 64% of all new cases.

As regards 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. 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. The risk of transmission from anal intercourse is especially high, estimated as 1.4–1.7% per act in both heterosexual and homosexual contacts.While the risk of transmission from oral sex is relatively low, it is still present.The risk from receiving oral sex has been described as "nearly nil" however a few cases have been reported. The per-act risk is estimated at 0–0.04% for receptive oral intercourse. 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.

Risk of transmission increases in the presence of many sexually transmitted infectionsand genital ulcers. Genital ulcers appear to increase the risk approximately fivefold. Other sexually transmitted infections, such as gonorrhea, chlamydia, trichomoniasis, and bacterial vaginosis, are associated with somewhat smaller increases in risk of transmission.

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

Commercial sex workers (including those in pornography) have an increased rate of HIV.Rough sex can be a factor associated with an increased risk of transmission. 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.

Body fluids

The second most frequent mode of HIV transmission is via blood and blood products.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 drug injection is between 0.63 and 2.4% per act, with an average of 0.8%.The risk of acquiring HIV from a needle stick from an HIV-infected person is estimated as 0.3% (about 1 in 333) per act and the risk following mucus membrane exposure to infected blood as 0.09% (about 1 in 1000) per act. In the United States intravenous drug users made up 12% of all new cases of HIV in 2009, and in some areas more than 80% of people who inject drugs are HIV positive.

HIV is transmitted in about 93% of blood transfusions involving infected blood. In developed countries the risk of acquiring HIV from a blood transfusion is extremely low (less than one in half a million) where improved donor selection and HIV screening is performed;for example, in the UK the risk is reported at one in five million. In low income countries, only half of transfusions may be appropriately screened (as of 2008), and it is estimated that up to 15% of HIV infections in these areas come from transfusion of infected blood and blood products, representing between 5% and 10% of global infections.

Unsafe medical injections play a significant role in HIV spread in sub-Saharan Africa. In 2007, between 12 and 17% of infections in this region were attributed to medical syringe use.The World Health Organisation estimates the risk of transmission as a result of a medical injection in Africa at 1.2%. Significant risks are also associated with invasive procedures, assisted delivery, and dental care in this area of the world.

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

Mother-to-child

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

Virology

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.

HIV is a member of the genus Lentivirus, part of the family Retroviridae. 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. 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. Once integrated, the virus may become latent, allowing the virus and its host cell to avoid detection by the immune system. 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.

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, 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.

Pathophysiology

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.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.

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.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.

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. 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. A specific genetic change that alters the CCR5 protein when present in both chromosomes very effectively prevents HIV-1 infection.

HIV seeks out and destroys CCR5 expressing CD4+ T cells during acute infection. A vigorous immune response eventually controls the infection and initiates the clinically latent phase. CD4+ T cells in mucosal tissues remain particularly affected. Continuous HIV replication causes a state of generalized immune activation persisting throughout the chronic phase. 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.

Diagnosis

HIV/AIDS is diagnosed via laboratory testing and then staged based on the presence of certain signs or symptoms. 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. Additionally testing is recommended for all those at high risk, which includes anyone diagnosed with a sexually transmitted illness. 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.

HIV testing

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

Antibody tests in children younger than 18 months are typically inaccurate due to the continued presence of maternal antibodies. Thus HIV infection can only be diagnosed by PCR testing for HIV RNA or DNA, or via testing for the p24 antigen. 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.  In sub-Saharan Africa as of 2007–2009 between 30 and 70% of the population was aware of their HIV status. In 2009, between 3.6 and 42% of men and women in Sub-Saharan countries were tested which represented a significant increase compared to previous years.

Classifications of HIV infection

Two main clinical staging systems are used to classify HIV and HIV-related disease for surveillance purposes: the WHO disease staging system for HIV infection and disease, and the CDC classification system for HIV infection. The CDC's classification system is more frequently adopted in developed countries. Since the 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.

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

Primary HIV infection: May be either asymptomatic or associated with acute retroviral syndrome.

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. May include generalized lymph node enlargement.

Stage II: Mild symptoms which may include minor mucocutaneous manifestations and recurrent upper respiratory tract infections. A CD4 count of less than 500/µl.

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.

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.

The United States Center for Disease Control and Prevention also created a classification system for HIV, and updated it in 2008. This system classifies HIV infections based on CD4 count and clinical symptoms, and describes the infection in three stages:

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

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.

Prevention

Sexual contact

Consistent condom use reduces the risk of HIV transmission by approximately 80% over the long term. When condoms are used consistently by a couple in which one person is infected, the rate of HIV infection is less than 1% per year. There is some evidence to suggest that female condoms may provide an equivalent level of protection. Application of a vaginal gel containing tenofovir (a reverse transcriptase inhibitor) immediately before sex seems to reduce infection rates by approximately 40% among African women. By contrast, use of the spermicide nonoxynol-9 may increase the risk of transmission due to its tendency to cause vaginal and rectal irritation. Circumcision in Sub-Saharan Africa "reduces the acquisition of HIV by heterosexual men by between 38% and 66% over 24 months". Based on these studies, the World Health Organization and UNAIDS both recommended male circumcision as a method of preventing female-to-male HIV transmission in 2007. Whether it protects against male-to-female transmission is disputed and whether it is of benefit in developed countries and among men who have sex with men is undetermined. Some experts fear that a lower perception of vulnerability among circumcised men may cause more sexual risk-taking behavior, thus negating its preventive effects.

Programs encouraging sexual abstinence do not appear to affect subsequent HIV risk. Evidence for a benefit from peer education is equally poor. Comprehensive sexual education provided at school may decrease high risk behavior. 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. It is not known whether treating other sexually transmitted infections is effective in preventing HIV.

Pre-exposure

Treating people with HIV whose CD4 count ≥ 350cells/µL with antiretrovirals protects 96% of their partners from infection. This is about a 10 to 20 fold reduction in transmission risk. Pre-exposure prophylaxis 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. 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.

Universal precautions within the health care environment are believed to be effective in decreasing the risk of HIV. 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.

Post-exposure

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). The use of the single agent zidovudine reduces the risk of a HIV infection five-fold following a needle-stick injury. As of 2013, the prevention regime recommended in the United States consists of three medications—tenofovir, emtricitabine and raltegravir—as this may reduce the risk further.

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. The duration of treatment is usually four weeks 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%).

Mother-to-child

Programs to prevent the vertical transmission of HIV (from mothers to children) can reduce rates of transmission by 92–99%. 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. 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. If exclusive breastfeeding is carried out, the provision of extended antiretroviral prophylaxis to the infant decreases the risk of transmission.

Vaccination

As of 2012 there is no effective vaccine for HIV or AIDS. A single trial of the vaccine RV 144 published in 2009 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. Further trials of the RV 144 vaccine are ongoing.

Management

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

Antiviral therapy

Current HAART options are combinations (or "cocktails") consisting of at least three medications belonging to at least two types, or "classes," of antiretroviral agents. Initially treatment is typically a non-nucleoside reverse transcriptase inhibitor (NNRTI) plus two nucleoside analogue reverse transcriptase inhibitors (NRTIs). Typical NRTIs include: zidovudine (AZT) or tenofovir (TDF) and lamivudine (3TC) or emtricitabine (FTC). Combinations of agents which include a protease inhibitors (PI) are used if the above regime loses effectiveness.

When to start antiretroviral therapy is subject to debate. The World Health Organization, European guidelines and the United States recommends antiretrovirals in all adolescents, adults and pregnant women with a CD4 count less than 350/µl or those with symptoms regardless of CD4 count. This is supported by the fact that beginning treatment at this level reduces the risk of death. The United States in addition recommends them for all HIV-infected people regardless of CD4 count or symptoms; however it makes this recommendation with less confidence for those with higher counts. While the WHO also recommends treatment in those who are co-infected with tuberculosis and those with chronic active hepatitis B. Once treatment is begun it is recommended that it is continued without breaks or "holidays". Many people are diagnosed only after treatment ideally should have begun. The desired outcome of treatment is a long term plasma HIV-RNA count below 50 copies/ mL. Levels to determine if treatment is effective are initially recommended after four weeks and once levels fall below 50 copies/mL checks every three to six months are typically adequate. Inadequate control is deemed to be greater than 400 copies/mL. Based on these criteria treatment is effective in more than 95% of people during the first year.

Benefits of treatment include a decreased risk of progression to AIDS and a decreased risk of death. In the developing world treatment also improves physical and mental health. With treatment there is a 70% reduced risk of acquiring tuberculosis. Additional benefits include a decreased risk of transmission of the disease to sexual partners and a decrease in mother-to-child transmission. The effectiveness of treatment depends to a large part on compliance. Reasons for non-adherence include poor access to medical care, inadequate social supports, mental illness and drug abuse. The complexity of treatment regimens (due to pill numbers and dosing frequency) and adverse effects may reduce adherence. Even though cost is an important issue with some medications, 47% of those who needed them were taking them in low and middle income countries as of 2010 and the rate of adherence is similar in low-income and high-income countries.

Specific adverse events are related to the antiretroviral agent taken. Some relatively common adverse events include: lipodystrophy syndrome, dyslipidemia, and diabetes mellitus, especially with protease inhibitors. Other common symptoms include diarrhea, and an increased risk of cardiovascular disease. Newer recommended treatments are associated with fewer adverse effects. Certain medications may be associated with birth defects and therefore may be unsuitable for women hoping to have children.Treatment recommendations for children are slightly different from those for adults. In the developing world, as of 2010, 23% of children who were in need of treatment had access. Both the World Health Organization and the United States recommend treatment for all children less than twelve months of age. The United States recommends in those between one year and five years of age treatment in those with HIV RNA counts of greater than 100,000 copies/mL, and in those more than five years treatments when CD4 counts are less than 500/µl.

Opportunistic infections

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. 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. 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. 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. People with substantial immunosuppression are also advised to receive prophylactic therapy for toxoplasmosis and Cryptococcus meningitis.  Appropriate preventive measures have reduced the rate of these infections by 50% between 1992 and 1997.

Alternative medicine

In the US, approximately 60% of people with HIV use various forms of complementary or alternative medicine, even though the effectiveness of most of these therapies has not been established. With respect to dietary advice and AIDS some evidence has shown a benefit from micronutrient supplements. Evidence for supplementation with selenium is mixed with some tentative evidence of benefit. There is some evidence that vitamin A supplementation in children reduces mortality and improves growth. In Africa in nutritionally compromised pregnant and lactating women a multivitamin supplementation has improved outcomes for both mothers and children. Dietary intake of micronutrients at RDA levels by HIV-infected adults is recommended by the World Health Organization. The WHO further states that several studies indicate that supplementation of vitamin A, zinc, and iron can produce adverse effects in HIV positive adults. There is not enough evidence to support the use of herbal medicines.

Prognosis

HIV/AIDS has become a chronic rather than an acutely fatal disease in many areas of the world. Prognosis varies between people, and both the CD4 count and viral load are useful for predicted outcomes. Without treatment, average survival time after infection with HIV is estimated to be 9 to 11 years, depending on the HIV subtype. After the diagnosis of AIDS, if treatment is not available, survival ranges between 6 and 19 months. 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. This is between two thirds and nearly that of the general population. If treatment is started late in the infection, prognosis is not as good: for example, if treatment is begun following the diagnosis of AIDS, life expectancy is ~10–40 years. Half of infants born with HIV die before two years of age without treatment.

The primary causes of death from HIV/AIDS are opportunistic infections and cancer, both of which are frequently the result of the progressive failure of the immune system. Risk of cancer appears to increase once the CD4 count is below 500/μL. The rate of clinical disease progression varies widely between individuals and has been shown to be affected by a number of factors such as a person's susceptibility and immune function; their access to health care, the presence of co-infections; and the particular strain (or strains) of the virus involved.

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. HIV is also one of the most important risk factors for tuberculosis. Hepatitis C is another very common co-infection where each disease increases the progression of the other. The two most common cancers associated with HIV/AIDS are Kaposi's sarcoma and AIDS-related non-Hodgkin's lymphoma.

Even with anti-retroviral treatment, over the long term HIV-infected people may experience neurocognitive disorders, osteoporosis, neuropathy, cancers, nephropathy, and cardiovascular disease. It is not clear whether these conditions result from the HIV infection itself or are adverse effects of treatment.

Epidemiology

HIV/AIDS is a global pandemic. As of 2012, approximately 35.3 million people have HIV worldwide with the number of new infections that year being about 2.3 million. This is down from 3.1 million new infections in 2001. Of these approximately 16.8 million are women and 3.4 million are less than 15 years old. It resulted in about 1.6 million deaths in 2012, down from a peak of 2.2 million in 2005.

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. This means that about 5% of the adult population is infected and it is believed to be the cause of 10% of all deaths in children. Here in contrast to other regions women compose nearly 60% of cases. South Africa has the largest population of people with HIV of any country in the world at 5.9 million. 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. 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.

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. Approximately 2.4 million of these cases are in India.

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. In the United Kingdom as of 2009 there were approximately 86,500 cases which resulted in 516 deaths. In Canada as of 2008 there were about 65,000 cases causing 53 deaths. Between the first recognition of AIDS in 1981 and 2009 it has led to nearly 30 million deaths. 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%.

Discovery

AIDS was first clinically observed in 1981 in the United States. 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. Soon thereafter, an unexpected number of gay men developed a previously rare skin cancer called Kaposi's sarcoma (KS). 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.

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

In 1983, two separate research groups led by Robert Gallo and Luc Montagnier independently declared that a novel retrovirus may have been infecting AIDS patients, and published their findings in the same issue of the journal Science. Gallo claimed that a virus his group had isolated from an AIDS patient 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 patient 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). As these two viruses turned out to be the same, in 1986, LAV and HTLV-III were renamed HIV.

Origins

Both HIV-1 and HIV-2 are believed to have originated in non-human primates in West-central Africa and were transferred to humans in the early 20th century. 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).[190][191] 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). 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. 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.

There is evidence that humans who participate in bushmeat activities, either as hunters or as bushmeat vendors, commonly acquire SIV. 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. 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.

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. 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. 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.

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.

The earliest well documented case of HIV in a human dates back to 1959 in the Congo. The virus may have been present in the United States as early as 1966, 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. 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 gay male residents of New York and San Francisco was estimated at 5%, suggesting that several thousand individuals in the country had been infected.

Society and culture

Stigma

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. 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.

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

Instrumental AIDS stigma — a reflection of the fear and apprehension that are likely to be associated with any deadly and transmissible illness.

Symbolic AIDS stigma—the use of HIV/AIDS to express attitudes toward the social groups or lifestyles perceived to be associated with the disease.

Courtesy AIDS stigma—stigmatization of people connected to the issue of HIV/AIDS or HIV-positive people.

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.

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. There is also a perceived association between AIDS and all male-male sexual behavior, including sex between uninfected men. However, the dominant mode of spread worldwide for HIV remains heterosexual transmission.

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

Economic impact

HIV/AIDS affects the economics of both individuals and countries. The gross domestic product of the most affected countries has decreased due to the lack of human capital. 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. Many are cared for by elderly grandparents.

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.

At the household level, AIDS causes both loss of income and increased spending on healthcare. A study in Côte d'Ivoire showed that households with an HIV/AIDS patient 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.

Religion and AIDS

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. 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.

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. 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.

Media portrayal

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. A notable British casualty of AIDS that year was Nicholas Eden, a gay politician and son of the late prime minister Anthony Eden. 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. However he had been diagnosed as HIV positive during 1987. 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 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. He died, aged 49, as a result on 6 February 1993.

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. 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. Aziga was convicted of first-degree murder and is liable to a life sentence.

Denial, conspiracies, and misconceptions

A small group of individuals continue to dispute the connection between HIV and AIDS, the existence of HIV itself, or the validity of HIV testing and treatment methods. These claims, known as AIDS denialism, have been examined and rejected by the scientific community. 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. Operation INFEKTION was a worldwide Soviet active measures operation to spread information that the United States had created HIV/AIDS. Surveys show that a significant number of people believed – and continue to believe – in such claims.

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, and that HIV can infect only homosexual men and drug users. Other misconceptions are that any act of anal intercourse between two uninfected gay men can lead to HIV infection, and that open discussion of homosexuality and HIV in schools will lead to increased rates of homosexuality and AIDS.

History of HIV/AIDS

AIDS is caused by the human immunodeficiency virus (HIV), which originated in non-human primates in Sub-Saharan Africa and was transferred to humans during the late 19th or early 20th century.

Two types of HIV exist: HIV-1 and HIV-2. HIV-1 is more virulent, is more easily transmitted and is the cause of the vast majority of HIV infections globally. The pandemic strain of HIV-1 is closely related to a virus found in the chimpanzees of the subspecies Pan troglodytes troglodytes, which lives in the forests of the Central African nations of Cameroon, Equatorial Guinea, Gabon, Republic of Congo (or Congo-Brazzaville), and Central African Republic. HIV-2 is less transmittable and is largely confined to West Africa, along with its closest relative, a virus of the sooty mangabey (Cercocebus atys atys), an Old World monkey inhabiting southern Senegal, Guinea-Bissau, Guinea, Sierra Leone, Liberia, and western Ivory Coast.

Transmission from non-humans to humans

Most HIV researchers agree that HIV evolved at some point from the closely related Simian immunodeficiency virus (SIV), and that SIV or HIV (post mutation) was transferred from non-human primates to humans in the recent past (as a type of zoonosis). Research in this area is conducted using molecular phylogenetics, comparing viral genomic sequences to determine relatedness.

HIV-1 from chimpanzees and gorillas to humans

Scientists generally accept that the known strains (or groups) of HIV-1 are most closely related to the simian immunodeficiency viruses (SIVs) endemic in wild ape populations of West Central African forests. Particularly, each of the known HIV-1 strains is either closely related to the SIV that infects the chimpanzee subspecies Pan troglodytes troglodytes (SIVcpz), or to the SIV that infects Western lowland gorillas (Gorilla gorilla gorilla), called SIVgor. The pandemic HIV-1 strain (group M or Main) and a very rare strain only found in a few Cameroonian people (group N) are clearly derived from SIVcpz strains endemic in Pan troglodytes troglodytes chimpanzee populations living in Cameroon.  Another very rare HIV-1 strain (group P) is clearly derived from SIVgor strains of Cameroon. Finally, the primate ancestor of HIV-1 group O, a strain infecting tens of thousands of people mostly from Cameroon but also from neighboring countries, is still uncertain, but there is evidence that it is either SIVcpz or SIVgor. The pandemic HIV-1 group M is most closely related to the SIVcpz collected from the southeastern rain forests of Cameroon (modern East Province) near the Sangha River. Thus, this region is presumably where the virus was first transmitted from chimpanzees to humans. However, reviews of the epidemiological evidence of early HIV-1 infection in stored blood samples, and of old cases of AIDS in Central Africa have led many scientists to believe that HIV-1 group M early human center was probably not in Cameroon, but rather farther south in the Democratic Republic of the Congo, more probably in its capital city, Kinshasa.

Using HIV-1 sequences preserved in human biological samples along with estimates of viral mutation rates, scientists calculate that the jump from chimpanzee to human probably happened during the late 19th or early 20th century, a time of rapid urbanisation and colonisation in equatorial Africa. Exactly when the zoonosis occurred is not known. Some molecular dating studies suggest that HIV-1 group M had its most recent common ancestor (MRCA) (that is, started to spread in the human population) in the early 20th century, probably between 1915 and 1941.  A study published in 2008, analyzing viral sequences recovered from a recently discovered biopsy made in Kinshasa, in 1960, along with previously known sequences, suggested a common ancestor between 1873 and 1933 (with central estimates varying between 1902 and 1921).

Genetic recombination had earlier been thought to "seriously confound" such phylogenetic analysis, but later "work has suggested that recombination is not likely to systematically bias [results]", although recombination is "expected to increase variance". The results of a 2008 phylogenetics study support the later work and indicate that HIV evolves "fairly reliably".

HIV-2 from sooty mangabeys to humans

Similar research has been undertaken with SIV strains collected from several wild sooty mangabey (Cercocebus atys atys) (SIVsmm) communities of the West African nations of Sierra Leone, Liberia, and Ivory Coast. The resulting phylogenetic analyses show that the viruses most closely related to the two strains of HIV-2 which spread considerably in humans (HIV-2 groups A and B) are the SIVsmm found in the sooty mangabeys of the Tai forest, in western Ivory Coast.

There are six additional known HIV-2 groups, each having been found in just one person. They all seem to derive from independent transmissions from sooty mangabeys to humans. Groups C and D have been found in two people from Liberia, groups E and F have been discovered in two people from Sierra Leone, and groups G and H have been detected in two people from the Ivory Coast. These HIV-2 strains are probably dead-end infections, and each of them is most closely related to SIVsmm strains from sooty mangabeys living in the same country where the human infection was found.

Molecular dating studies suggest that both the epidemic groups (A and B) started to spread among humans between 1905 and 1961 (with the central estimates varying between 1932 and 1945).

Bushmeat practice

According to the natural transfer theory (also called 'Hunter Theory' or 'Bushmeat Theory'), the "simplest and most plausible explanation for the cross-species transmission" of SIV or HIV (post mutation), the virus was transmitted from an ape or monkey to a human when a hunter or bushmeat vendor/handler was bitten or cut while hunting or butchering the animal. The resulting exposure to blood or other bodily fluids of the animal can result in SIV infection. A recent serological survey showed that human infections by SIV are not rare in Central Africa: the percentage of people showing seroreactivity to antigens — evidence of current or past SIV infection — was 2.3% among the general population of Cameroon, 7.8% in villages where bushmeat is hunted or used, and 17.1% in the most exposed people of these villages. How the SIV virus would have transformed into HIV after infection of the hunter or bushmeat handler from the ape/monkey is still a matter of debate, although natural selection would favor any viruses capable of adjusting so that they could infect and reproduce in the T cells of a human host.

Emergence

Conditions for successful zoonosis

Zoonosis (transfer of a pathogen from non-human animals to humans) and subsequent spread of the pathogen between humans, requires the following conditions:

a human population;

a nearby population of a host animal;

an infectious pathogen in the host animal that can spread from animal to human;

interaction between the species to transmit enough of the pathogen to humans to establish a human foothold, which could have taken millions of individual exposures;

ability of the pathogen to spread from human to human (perhaps acquired by mutation);

some process allowing the pathogen to disperse widely, preventing the infection from "burning out" by either killing off its human hosts or provoking immunity in a local population of humans.

The unresolved issues about HIV origins and emergence

It is clear that the several HIV-1 and HIV-2 strains descend from SIVcpz, SIVgor, and SIVsmm viruses, and that bushmeat practice provides the most plausible venue for cross-species transfer to humans. However, some loose ends remain unresolved.

It is not yet explained why only four HIV groups (HIV-1 groups M and O, and HIV-2 groups A and B) spread considerably in human populations, despite bushmeat practices being very widespread in Central and West Africa, and the resulting human SIV infections being common.

It remains also unexplained why all epidemic HIV groups emerged in humans nearly simultaneously, and only in the 20th century, despite very old human exposure to SIV (a recent phylogenetic study demonstrated that SIV is at least tens of thousands of years old).

The discovery of the main HIV / SIV phylogenetic relationships permits explaining broadly HIV biogeography: the early centers of the HIV-1 groups were in Central Africa, where the primate reservoirs of the related SIVcpz and SIVgor viruses (chimpanzees and gorillas) exist; similarly, the HIV-2 groups had their centers in West Africa, where sooty mangabeys, which harbor the related SIVsmm virus, exist. However these relationships do not explain more detailed patterns of biogeography, such as why epidemic HIV-2 groups (A and B) only evolved in the Ivory Coast, which is only one of six countries harboring the sooty mangabey. It is also unclear why the SIVcpz endemic in the chimpanzee subspecies Pan troglodytes schweinfurthii (inhabiting the Democratic Republic of Congo, Central African Republic, Rwanda, Burundi, Uganda, and Tanzania) did not spawn an epidemic HIV-1 strain to humans, while the Democratic Republic of Congo was the main center of HIV-1 group M, a virus descended from SIVcpz strains of a subspecies (Pan troglodytes troglodytes) that does not exist in this country.

Theories of HIV origin and epidemic emergence

Several of the theories of HIV origin put forward (described below) attempt to explain the unresolved loose ends described in the previous section. Most of them accept the (above described) established knowledge of the HIV/SIV phylogenetic relationships, and also accept that bushmeat practice was the most likely cause of the initial transfer to humans. All of them propose that the simultaneous epidemic emergences of four HIV groups in the late 19th-early 20th century, and the lack of previous emergences, are explained by new factor(s) that appeared in the relevant African regions in that timeframe. These new factor(s) would have acted either to increase human exposures to SIV, to help it to adapt to the human organism by mutation (thus enhancing its between-humans transmissibility), or to cause an initial burst of transmissions crossing an epidemiological threshold, and therefore increasing the odds of continued spread.

Social changes and urbanization

It was proposed by Beatrice Hahn, Paul Sharp, and colleagues that "[the epidemic emergence of HIV] most likely reflects changes in population structure and behaviour in Africa during the 20th century and perhaps medical interventions that provided the opportunity for rapid human-to-human spread of the virus".  After the Scramble for Africa started in the 1880s, European colonial powers established cities, towns, and other colonial stations. A largely masculine labor force was hastily recruited to work in fluvial and sea ports, railways, other infrastructures, and in plantations. This disrupted traditional tribal values, and favored sexual promiscuity. In the nascent cities women felt relatively liberated from rural tribal rules and many remained unmarried or divorced during long periods, this being very rare in African traditional societies. This was accompanied by unprecedented increase in people's movements.

Michael Worobey and colleagues observed that the growth of cities had probably a role in the epidemic emergence of HIV, since the phylogenetic datations of the two older strains of HIV-1 (groups M and O), suggest that these viruses started to spread soon after the main Central African colonial cities were founded.

Heart of Darkness

Amit Chitnis, Diana Rawls, and Jim Moore proposed that HIV may have emerged epidemically as a result of the harsh conditions, forced labor, displacement, and unsafe injection and vaccination practices associated with colonialism, particularly in French Equatorial Africa. The workers in plantations, construction projects, and other colonial enterprises were supplied with bushmeat, this contributing to increase this activity, and then exposures to SIV. Several historical sources support the view that bushmeat hunting indeed increased, both because of the necessity to supply workers and because firearms became more widely available.

The colonial authorities also gave many vaccinations against smallpox, and injections, of which many would be made without sterilising the equipment between uses (unsafe or unsterile injections). Chitnis et al. proposed that both these parenteral risks and the prostitution associated with forced labor camps could have caused serial transmission (or serial passage) of SIV between humans (see discussion of this in the next section). In addition, they proposed that the conditions of extreme stress associated with forced labor could depress the immune system of workers, therefore prolonging the primary acute infection period of someone newly infected by SIV, thus increasing the odds of both adaptation of the virus to humans, and of further transmissions.

The authors predicted that HIV-1 originated in the area of French Equatorial Africa, and in the early 20th century (when the colonial abuses and forced labor were at their peak). Later researches proved these predictions mostly correct: HIV-1 groups M and O started to spread in humans in late 19th–early 20th century. And all groups of HIV-1 descend from either SIVcpz or SIVgor from apes living to the west of the Ubangi River, either in countries which belonged to the French Equatorial Africa federation of colonies, in Equatorial Guinea (then a Spanish colony), or in Cameroon (which was a German colony between 1884 and 1916, then fell to Allied forces in World War I, and had most of its area administered by France, in close association with French Equatorial Africa).

This theory was later dubbed 'Heart of Darkness' by Jim Moore, alluding to the book of the same title written by Joseph Conrad, the main focus of which is colonial abuses in equatorial Africa.

Unsterile injections

In several articles published since 2001, Preston Marx, Philip Alcabes, and Ernest Drucker proposed that HIV emerged because of rapid serial human-to-human transmission of SIV (after a bushmeat hunter or handler became SIV-infected) through unsafe or unsterile injections. Although both Chitnis et al. and Sharp et al. also suggested that this may have been one of the major risk factors at play in HIV emergence (see above), Marx et al. enunciated the underlying mechanisms in greater detail, and wrote the first review of the injection campaigns made in colonial Africa.

Central to Marx et al. argument is the concept of adaptation by serial passage (or serial transmission): an adventitious virus (or other pathogen) can increase its biological adaptation to a new host species if it is rapidly transmitted between hosts, while each host is still in the acute infection period. This process favors the accumulation of adaptive mutations more rapidly, therefore increasing the odds that a better adapted viral variant will appear in the host before the immune system suppresses the virus. Such better adapted variant could then survive in the human host for longer than the short acute infection period, in high numbers (high viral load), which would grant it more possibilities of epidemic spread.

Marx et al. reported experiments of cross-species transfer of SIV in captive monkeys (some of which made by themselves), in which the use of serial passage helped to adapt SIV to the new monkey species after passage by three or four animals.

In agreement with this model is also the fact that, while both HIV-1 and HIV-2 attain substantial viral loads in the human organism, adventitious SIV infecting humans seldom does so: people with SIV antibodies often have very low or even undetectable SIV viral load. This suggests that both HIV-1 and HIV-2 are adapted to humans, and serial passage could have been the process responsible for it.

Marx et al. proposed that unsterile injections (that is, injections where the needle or syringe is reused without sterilization or cleaning between uses), which were likely very prevalent in Africa, during both the colonial period and afterwards, provided the mechanism of serial passage that permitted HIV to adapt to humans, therefore explaining why it emerged epidemically only in the 20th century.

Massive injections of the antibiotic era

Marx et al. emphasize the massive number of injections administered in Africa after antibiotics were introduced (around 1950) as being the most likely implicated in the origin of HIV because, by these times (roughly in the period 1950 to 1970), injection intensity in Africa was maximal. They argued that a serial passage chain of 3 or 4 transmissions between humans is an unlikely event (the probability of transmission after a needle reuse is something between 0.3% and 2%, and only a few people have an acute SIV infection at any time), and so HIV emergence may have required the very high frequency of injections of the antibiotic era.

The molecular dating studies place the initial spread of the epidemic HIV groups before that time (see above). According to Marx et al., these studies could have overestimated the age of the HIV groups, because they depend on a molecular clock assumption, may not have accounted for the effects of natural selection in the viruses, and the serial passage process alone would be associated with strong natural selection.

The injection campaigns against sleeping sickness

David Gisselquist proposed that the mass injection campaigns to treat trypanosomiasis (sleeping sickness) in Central Africa were responsible for the emergence of HIV-1. Unlike Marx et al., Gisselquist argued that the millions of unsafe injections administered during these campaigns were sufficient to spread rare HIV infections into an epidemic, and that evolution of HIV through serial passage was not essential to the emergence of the HIV epidemic in the 20th century.

This theory focuses on injection campaigns that peaked in the period 1910–40, that is, around the time the HIV-1 groups started to spread. It also focuses on the fact that many of the injections in these campaigns were intravenous (which are more likely to transmit SIV/HIV than subcutaneous or intramuscular injections), and many of the patients received many (often more than 10) injections per year, therefore increasing the odds of SIV serial passage.

Other early injection campaigns

Jacques Pépin and Annie-Claude Labbé reviewed the colonial health reports of Cameroon and French Equatorial Africa for the period 1921–59, calculating the incidences of the diseases requiring intravenous injections. They concluded that trypanosomiasis, leprosy, yaws, and syphilis were responsible for most intravenous injections. Schistosomiasis, tuberculosis, and vaccinations against smallpox represented lower parenteral risks: schistosomiasis cases were relatively few; tuberculosis patients only became numerous after mid century; and there were few smallpox vaccinations in the lifetime of each person.

The authors suggested that the very high prevalence of the Hepatitis C virus in southern Cameroon and forested areas of French Equatorial Africa(around 40–50%) can be better explained by the unsterile injections used to treat yaws, because this disease was much more prevalent than syphilis, trypanosomiasis, and leprosy in these areas. They suggested that all these parenteral risks caused, not only the massive spread of Hepatitis C, but also the spread of other pathogens, and the emergence of HIV-1: "the same procedures could have exponentially amplified HIV-1, from a single hunter/cook occupationally infected with SIVcpz to several thousand patients treated with arsenicals or other drugs, a threshold beyond which sexual transmission could prosper." They do not suggest specifically serial passage as the mechanism of adaptation.

According to Pépin's 2011 book, The Origins of AIDS, the virus can be traced to a central African bush hunter in 1921, with colonial medical campaigns using improperly sterilized syringe and needles playing a key role in enabling a future epidemic. Pépin concludes that AIDS spread silently in Africa for decades, fueled by urbanization and prostitution since the initial cross-species infection. Pépin also claims that the virus was brought to the Americas by a Haitian teacher returning home from Zaire in the 1960s. Sex tourism and contaminated blood transfusion centers ultimately propelled AIDS to public’s consciousness in the 80s and a worldwide pandemic.

Genital ulcer diseases and sexual promiscuity

João Dinis de Sousa, Viktor Müller, Philippe Lemey, and Anne-Mieke Vandamme proposed that HIV became epidemic through sexual serial transmission, in nascent colonial cities, helped by a high frequency of genital ulcers, caused by genital ulcer diseases (GUD). GUD are simply sexually transmitted diseases that cause genital ulcers; examples are syphilis, chancroid, lymphogranuloma venereum, and genital herpes. These diseases increase the probability of HIV transmission dramatically, from around 0.01–0.1% to 4–43% per heterosexual act, because the genital ulcers provide a portal of viral entry, and contain many activated T cells expressing the CCR5 co-receptor, the main cell targets of HIV.

The probable time interval of cross-species transfer

Sousa et al. use molecular dating techniques to estimate the time when each HIV group split from its closest SIV lineage. Each HIV group necessarily crossed to humans between this time and the time when it started to spread (the time of the MRCA), because after the MRCA certainly all lineages were already in humans, and before the split with the closest simian strain, the lineage was in a simian. HIV-1 groups M and O, split from their closest SIVs around 1876 (1847–1907), 1741 (1606–1870), respectively. HIV-2 did so around 1889 (1856–1922). This information, together with the datations of the HIV groups' MRCAs (described above) mean that all HIV groups likely crossed to humans in late 19th—early 20th century.

Strong GUD incidence in nascent colonial cities

The authors reviewed colonial medical articles and archived medical reports of the countries at or near the ranges of chimpanzees, gorillas and sooty mangabeys, and found that genital ulcer diseases peaked in the colonial cities during their early growth period (up to 1935). The colonial authorities recruited men to work in railways, fluvial and sea ports, and other infrastructure projects, and most of these men did not bring their wives with them. Then, the highly male-biased sex ratio favoured prostitution, which in its turn caused an explosion of GUD (especially syphilis and chancroid). After the mid-1930s, people's movements were more tightly controlled, and mass surveys and treatments (of arsenicals and other drugs) were organized, and so the GUD incidences started to decline. They declined even further after World War II, because of the heavy use of antibiotics, so that, by the late 1950s, Kinshasa (which is the probable center of HIV-1 group M) had a very low GUD incidence. Similar processes happened in the cities of Cameroon and Ivory Coast, where HIV-1 group O and HIV-2 respectively evolved.

Therefore, the peak GUD incidences in cities have a good temporal coincidence with the period when all main HIV groups crossed to humans and started to spread. In addition, the authors gathered evidence that syphilis and the other GUDs were, like injections, absent from the densely forested areas of Central and West Africa before organized colonialism socially disrupted these areas (starting in the 1880s). Thus, this theory also potentially explains why HIV emerged only after late 19th century.

Female circumcision

Uli Linke has argued that the practice of female circumcision is responsible for the high incidence of AIDS in Africa, since intercourse with a circumcised female is conducive to exchange of blood.

Male circumcision distribution and HIV origins

Male circumcision may reduce the probability of HIV acquisition by men (see article Circumcision and HIV). Leaving aside blood transfusions, the highest HIV-1 transmissibility ever measured was from GUD-suffering female prostitutes to uncircumcised men—the measured risk was 43% in a single sexual act. Sousa et al. reasoned that the adaptation and epidemic emergence of each HIV group may have required such extreme conditions, and thus reviewed the existing ethnographic literature for patterns of male circumcision and hunting of apes and monkeys for bushmeat, focusing on the period 1880–1960, and on most of the 318 ethnic groups living in Central and West Africa. They also collected censuses and other literature showing the ethnic composition of colonial cities in this period. Then, they estimated the circumcision frequencies of the Central African cities over time.

Sousa et al. charts reveal that male circumcision frequencies were much lower in several cities of western and central Africa in the early 20th century than they are currently. The reason is that many ethnic groups not performing circumcision by that time gradually adopted it, to imitate other ethnic groups and enhance the social acceptance of their boys (colonialism produced massive intermixing between African ethnic groups). About 15–30% of men in Kinshasa and Douala in early 20th century should be uncircumcised, and these cities were the probable centers of HIV-1 groups M and O, respectively.

The authors studied early circumcision frequencies in 12 cities of Central and West Africa, to test if this variable correlated with HIV emergence. This correlation was strong for HIV-2: among 6 West African cities that could have received immigrants infected with SIVsmm, the two cities from the Ivory Coast studied (Abidjan and Bouaké) had much higher frequency of uncircumcised men (60–85%) than the others, and epidemic HIV-2 groups emerged initially in this country only. This correlation was less clear for HIV-1 in Central Africa.

Computer simulations of HIV emergence

Sousa et al. then built computer simulations to test if an 'ill-adapted SIV' (meaning a simian immunodeficiency virus already infecting a human but incapable of transmission beyond the short acute infection period) could spread in colonial cities. The simulations used parameters of sexual transmission obtained from the current HIV literature. They modelled people's 'sexual links', with different levels of sexual partner change among different categories of people (prostitutes, single women with several partners a year, married women, and men), according to data obtained from modern studies of sexual promiscuity in African cities. The simulations let the parameters (city size, proportion of people married, GUD frequency, male circumcision frequency, and transmission parameters) vary, and explored several scenarios. Each scenario was run 1,000 times, to test the probability of SIV generating long chains of sexual transmission. The authors postulated that such long chains of sexual transmission were necessary for the SIV strain to adapt better to humans, becoming a HIV capable of further epidemic emergence.

The main result was that genital ulcer frequency was by far the most decisive factor. For the GUD levels prevailing in Kinshasa, in early 20th century, long chains of SIV transmission had a high probability. For the lower GUD levels existing in the same city in the late 1950s (see above), they were much less likely. And without GUD (a situation typical of villages in forested equatorial Africa before colonialism) SIV could not spread at all. City size was not an important factor. The authors propose that these findings explain the temporal patterns of HIV emergence: no HIV emerging in tens of thousands of years of human slaughtering of apes and monkeys, several HIV groups emerging in the nascent, GUD-riddled, colonial cities, and no epidemically successful HIV group emerging in mid-20th century, when GUD was more controlled, and cities were much bigger.

Male circumcision had little to moderate effect in their simulations, but given the geographical correlation found, the authors propose that it could have had an indirect role, either by increasing genital ulcer disease itself (it is known that syphilis, chancroid, and several other GUDs have higher incidences in uncircumcised men), or by permitting further spread of the HIV strain, after the first chains of sexual transmission permitted adaptation to the human organism.

One of the main advantages of this theory is stressed by the authors: "It [the theory] also offers a conceptual simplicity because it proposes as causal factors for SIV adaptation to humans and initial spread the very same factors that most promote the continued spread of HIV nowadays: promiscuous sex, particularly involving sex workers, GUD, and possibly lack of circumcision."

Iatrogenic and other theories

Iatrogenic theories propose that medical interventions were responsible for HIV origins. By proposing factors that only appeared in Central and West Africa after the late 19th century, they seek to explain why all HIV groups also started after that.

The theories centered on the role of parenteral risks, such as unsterile injections, transfusions, or smallpox vaccinations are accepted as plausible by most scientists of the field, and were already reviewed above.

Discredited HIV/AIDS origins theories include several iatrogenic theories, such as Edward Hooper's 1999 claim that early oral polio vaccines, contaminated with a chimpanzee virus, caused the Central African outbreak.

Pathogenicity of SIV in non-human primates

In most non-human primate species, natural SIV infection does not cause a fatal disease (but see below). Comparison of the gene sequence of SIV with HIV should therefore give us information about the factors necessary to cause disease in humans. The factors that determine the virulence of HIV as compared to most SIVs are only now being elucidated. Non-human SIVs contain a nef gene that down-regulates CD3, CD4, and MHC class I expression; most non-human SIVs therefore do not induce immunodeficiency; the HIV-1 nef gene however has lost its ability to down-regulate CD3, which results in the immune activation and apoptosis that is characteristic of chronic HIV infection.

In addition, a long term survey of chimpanzees naturally infected with SIVcpz in Gombe, Tanzania, found that, contrary to the previous paradigm, chimpanzees with SIVcpz infection do experience an increased mortality, and also suffer from a Human AIDS-like illness. SIV pathogenicity in wild animals could exist in other chimpanzee subspecies and other primate species as well, and stay unrecognized by lack of relevant long term studies.

History of spread

1959: David Carr

David Carr was an apprentice printer (usually referred to, mistakenly, as a sailor; Carr had served in the Navy between 1955 and 1957) from Manchester, England who died in October 1959 following the failure of his immune system; he succumbed to pneumonia. Doctors, baffled by what he had died from, preserved 50 of his tissue samples for inspection. In 1990, the tissues were found to be HIV-positive. However, in 1992, a second test by AIDS researcher David Ho found that the strain of HIV present in the tissues was similar to those found in 1990 rather than an earlier strain (which would have mutated considerably over the course of 30 years). He concluded that the DNA samples provided actually came from a 1990 AIDS patient. Upon retesting David Carr's tissues, he found no sign of the virus. [medical citation needed]

1959: Congolese man

One of the earliest documented HIV-1 infections was discovered in a preserved blood sample taken in 1959 from a man from Leopoldville, Belgian Congo (now Kinshasa, Democratic Republic of the Congo). However, it is unknown whether this anonymous person ever developed AIDS and died of its complications.

1960: Congolese woman

A second early documented HIV-1 infection was discovered in a preserved lymph node biopsy sample taken in 1960 from a woman from Leopoldville, Belgian Congo.

1969: Robert Rayford

In May 1969 a 15-year-old African-American male named Robert Rayford died at the St. Louis City Hospital from Kaposi's Sarcoma. In 1987 researchers at Tulane University School of Medicine detected "a virus closely related or identical to" HIV-1 in his preserved blood and tissues. The doctors who worked on his case at the time suspected he was a prostitute, though the patient did not discuss his sexual history with them in detail.

1969: Arvid Noe

In 1976, a Norwegian sailor, with the alias name Arvid Noe, his wife, and his nine-year-old daughter died of AIDS. The sailor had first presented symptoms in 1969, eight years after he first spent time in ports along the West African coastline. A gonorrhea infection during his first African voyage shows he was sexually active at this time. Tissue samples from the sailor and his wife were tested in 1988 and found to contain HIV-1 (Group O).

Spread to the western hemisphere

HIV-1 strains are thought to have arrived in the United States from Haiti in the late 1960s or early '70s. HIV-1 is believed to have arrived in Haiti from central Africa, possibly through professional contacts with the Democratic Republic of the Congo. The current consensus is that HIV was introduced to Haiti by an unknown individual or individuals who contracted it while working in the Democratic Republic of the Congo circa 1966, or from another person who worked there during that time. A mini-epidemic followed, and, circa 1969, yet another unknown individual brought HIV from Haiti to the United States. The vast majority of cases of AIDS outside sub-Saharan Africa can be traced back to that single patient (although numerous unrelated incidents of AIDS among Haitian immigrants to the U.S. were recorded in the early 1980s, and, as evidenced by the case of Robert Rayford, isolated incidents of this infection may have been occurring as early as 1966.) The virus eventually entered male gay communities in large United States cities, where a combination of sexual promiscuity (with individuals reportedly averaging over 11 unprotected sexual partners per year) and relatively high transmission rates associated with anal intercourse allowed it spread explosively enough to finally be noticed.

Because of the long incubation period of HIV (up to a decade or longer) before symptoms of AIDS appear, and because of the initially low incidence, HIV was not noticed at first. By the time the first reported cases of AIDS were found in large United States cities, the prevalence of HIV infection in some communities had passed 5%. Worldwide, HIV infection has spread from urban to rural areas, and has appeared in regions such as China and India.

Canadian flight attendant theory

A Canadian airline steward named Gaëtan Dugas was referred to as "Patient 0" in an early AIDS study by Dr. William Darrow of the Centers for Disease Control. Because of this, many people had considered Dugas to be responsible for bringing HIV to North America. This is not accurate, however, as HIV had spread long before Dugas began his career. This rumor may have started with Randy Shilts' 1987 book And the Band Played On (and the 1993 movie based on it, in which Dugas is referred to as AIDS' Patient Zero), but neither the book nor the movie state that he had been the first to bring the virus to North America. He was called "Patient Zero" because at least 40 of the 248 people known to be infected by HIV in 1983 had had sex with him, or with someone who had sexual intercourse with him.

1981: From GRID to AIDS

The AIDS epidemic officially began on June 5, 1981, when the U.S. Centers for Disease Control and Prevention in its Morbidity and Mortality Weekly Report newsletter reported unusual clusters of Pneumocystis pneumonia (PCP) caused by a form of Pneumocystis carinii (now recognized as a distinct species Pneumocystis jirovecii) in five homosexual men in Los Angeles.

Over the next 18 months, more PCP clusters were discovered among otherwise healthy men in cities throughout the country, along with other opportunistic diseases (such as Kaposi's sarcoma and persistent, generalized lymphadenopathy), common in immunosuppressed patients.

In June 1982, a report of a group of cases amongst gay men in Southern California suggested that a sexually transmitted infectious agent might be the etiological agent, and the syndrome was initially termed "GRID", or gay-related immune deficiency.

Health authorities soon realized that nearly half of the people identified with the syndrome were not homosexual men. The same opportunistic infections were also reported among hemophiliacs, heterosexual intravenous drug users, and Haitian immigrants—leading some researchers to call it the "4H" disease.

By August 1982, the disease was being referred to by its new CDC-coined name: Acquired Immune Deficiency Syndrome (AIDS).

Identification of the virus

May 1983: LAV

In May 1983, doctors from Dr. Luc Montagnier's team at the Pasteur Institute in France reported that they had isolated a new retrovirus from lymphoid ganglions that they believed was the cause of AIDS. The virus was later named lymphadenopathy-associated virus (LAV) and a sample was sent to the U.S. Centers for Disease Control, which was later passed to the National Cancer Institute (NCI).

May 1984: HTLV-III

In May 1984 a team led by Robert Gallo of the United States confirmed the discovery of the virus, but they renamed it human T lymphotropic virus type III (HTLV-III).

Jan 1985: both found to be the same

In January 1985 a number of more detailed reports were published concerning LAV and HTLV-III, and by March it was clear that the viruses were the same, were from the same source, and were the etiological agent of AIDS.

May 1986: the name HIV

In May 1986, the International Committee on Taxonomy of Viruses ruled that both names should be dropped and a new name, HIV (Human Immunodeficiency Virus), be used.

Nobel

Whether Gallo or Montagnier deserve more credit for the discovery of the virus that causes AIDS has been a matter of considerable controversy. Together with his colleague Françoise Barré-Sinoussi, Montagnier was awarded one half of the 2008 Nobel Prize in Physiology or Medicine for his "discovery of human immunodeficiency virus". Harald zur Hausen also shared the prize for his discovery that human papilloma virus leads to cervical cancer, but Gallo was left out. Gallo said that it was "a disappointment" that he was not named a co-recipient. Montagnier said he was "surprised" Gallo was not recognized by the Nobel Committee: "It was important to prove that HIV was the cause of AIDS, and Gallo had a very important role in that. I'm very sorry for Robert Gallo."

Classification

Since June 5, 1981, many definitions have been developed for epidemiological surveillance such as the Bangui definition and the 1994 expanded World Health Organization AIDS case definition.

Genetic studies

According to a 2008 Proceedings of the National Academy of Sciences study, a team led by Robert Shafer at Stanford University School of Medicine has discovered that the Gray Mouse Lemur has an endogenous lentivirus (the genus to which HIV belongs) in its genetic makeup. This suggests that lentiviruses have existed for at least 14 million years, much longer than the currently known existence of HIV. In addition, the time frame falls into place when Madagascar was still yet connected to what is now the African continent; the said lemurs later developed immunity to the virus strain and survived an era when the lentivirus was widespread among other mammalian. The study is being hailed as crucial, because it fills the blanks in the origin of the virus, as well as in its evolution, and may be important in the development of new antiviral drugs.

In 2010, researchers reported that SIV had infected monkeys in Bioko for at least 32,000 years. Previously it was thought that SIV infection in monkeys had happened over the past few hundred years. Scientists estimated that it would take a similar amount of time before humans adapted naturally to HIV infection in the way monkeys in Africa have adapted to SIV and not suffer any harm from the infection.

Discredited hypotheses

Other hypotheses for the origin of AIDS have been proposed. AIDS denialism argues that HIV or AIDS does not exist or that AIDS is not caused by HIV; some of its proponents believe that AIDS is caused by lifestyle, including sexuality or drug use, and not by HIV. Some conspiracy theories allege that HIV was created in a bioweapons laboratory, perhaps as an agent of genocide or an accident. These hypotheses have been rejected by scientific consensus.

Reference

http://www.msf.org/diseases/hiv-aids?gclid=CMyW7rLXqrsCFTMdtAodPx0A0g

http://en.wikipedia.org/wiki/HIV/AIDS

http://en.wikipedia.org/wiki/History_of_HIV/AIDS

http://en.wikipedia.org/wiki/HIV/AIDS_in_India

http://en.wikipedia.org/wiki/Signs_and_symptoms_of_HIV/AIDS

http://en.wikipedia.org/wiki/Misconceptions_about_HIV/AIDS

http://en.wikipedia.org/wiki/HIV/AIDS_in_South_Africa

http://en.wikipedia.org/wiki/Timeline_of_AIDS

http://en.wikipedia.org/wiki/HIV/AIDS_denialism

http://en.wikipedia.org/wiki/Misconceptions_about_HIV/AIDS

http://en.wikipedia.org/wiki/Virgin_cleansing_myth

http://en.wikipedia.org/wiki/Religion_and_HIV/AIDS

http://en.wikipedia.org/wiki/Economic_impact_of_HIV/AIDS

http://en.wikipedia.org/wiki/Discrimination_against_people_with_HIV/AIDS

http://en.wikipedia.org/wiki/Epidemiology_of_HIV/AIDS

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