Acquired immunodeficiency syndrome (AIDS)
Classification and external resources
The red ribbon is a symbol for solidarity with HIV-positive people and those living with AIDS.
ICD-10	B24
ICD-9	042
DiseasesDB	5938
MedlinePlus	000594
eMedicine	emerg/253
MeSH	D000163

Acquired immune deficiency syndrome or acquired immunodeficiency syndrome (AIDS) is a disease of the human immune system caused by the human immunodeficiency virus (HIV).^[1] The illness interferes with the immune system, making people with AIDS much more likely to get infections, including opportunistic infections and tumors that do not affect people with working immune systems. This susceptibility gets worse as the disease continues.

HIV is transmitted in a number of ways including: sexual intercourse (including oral sex and anal sex); contaminated blood transfusions and hypodermic needles; and exchange between mother and baby during pregnancy, childbirth, and breastfeeding. It can be transmitted by any contact of a mucous membrane or the bloodstream with a bodily fluid that has the virus in it, such as the blood, semen, vaginal fluid, preseminal fluid, or breast milk from an infected person.^[2][3]

Although treatments for HIV/AIDS can slow the course of the disease, there is no known cure or HIV vaccine. Antiretroviral treatment reduces both the deaths and new infections from HIV/AIDS, but these drugs are expensive and the medications are not available in all countries.^[4] Due to the difficulty in treating HIV infection, preventing infection is a key aim in controlling the AIDS pandemic, with health organizations promoting safe sex and needle-exchange programmes in attempts to slow the spread of the virus. The virus and disease are often referred to together as HIV/AIDS. The disease is a major health problem in many parts of the world, and is considered a pandemic, a disease outbreak that is not only present over a large area but is actively spreading.^[5] In 2009, the World Health Organization (WHO) estimated that there are 33.4 million people worldwide living with HIV/AIDS, with 2.7 million new HIV infections per year and 2.0 million annual deaths due to AIDS.^[6] As of 2010 approximately 34 million people have HIV globally.^[7] Of these approximately 16.8 million are women and 3.4 million are less than 15 years old.^[7] It results in about 1.8 million death from AIDS in 2010 down from 3.1 million in 2001.^[7] Since AIDS was first recognized in 1981 and 2009 it has led to nearly 30 million deaths.^[8]

Genetic research indicates that HIV originated in west-central Africa during the late nineteenth or early twentieth century.^[9][10] AIDS was first recognized by the Centers for Disease Control and Prevention (CDC) in 1981 and its cause, HIV, identified in the early 1980s.^[11]

Signs and symptoms[link]

Main symptoms of AIDS.

X-ray of pneumocystis pneumonia (PCP). There is increased white (opacity) in the lower lungs on both sides, characteristic of PCP.

The symptoms of AIDS are primarily the result of conditions that do not normally develop in individuals with healthy immune systems. Most of these conditions are opportunistic infections caused by bacteria, viruses, fungi and parasites that are normally controlled by the elements of the immune system that HIV damages.^[12] These infections affect nearly every organ system.

People with AIDS also have an increased risk of developing various cancers such as Kaposi's sarcoma, cervical cancer and cancers of the immune system known as lymphomas. Additionally, people with AIDS often have systemic symptoms of infection like fevers, sweats (particularly at night), swollen glands, chills, weakness, and weight loss.^[13][14] The specific opportunistic infections that AIDS patients develop depend in part on the prevalence of these infections in the geographic area in which the patient lives.

Pulmonary[link]

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

Before the advent of effective diagnosis, treatment and routine prophylaxis in Western countries, it was a common immediate cause of death. In developing countries, it is still one of the first indications of AIDS in untested individuals, although it does not generally occur unless the CD4 count is less than 200 cells per µL of blood.^[15]

Tuberculosis (TB) is unique among infections associated with HIV because it is transmissible to immunocompetent people via the respiratory route, and is not easily treatable once identified.^[16] Multidrug resistance is a serious problem. Tuberculosis with HIV co-infection (TB/HIV) is a major world health problem according to the World Health Organization: in 2007, 456,000 deaths among incident TB cases were HIV-positive, a third of all TB deaths and nearly a quarter of the estimated 2 million HIV deaths in that year.^[17] Even though its incidence has declined because of the use of directly observed therapy and other improved practices in Western countries, this is not the case in developing countries where HIV is most prevalent. In early-stage HIV infection (CD4 count >300 cells per µL), TB typically presents as a pulmonary disease. In advanced HIV infection, TB often presents atypically with extrapulmonary (systemic) disease a common feature. Symptoms are usually constitutional and are not localized to one particular site, often affecting bone marrow, bone, urinary and gastrointestinal tracts, liver, regional lymph nodes, and the central nervous system.^[18]

Gastrointestinal[link]

Esophagitis is an inflammation of the lining of the lower end of the esophagus (gullet or swallowing tube leading to the stomach). In HIV-infected individuals, this is normally due to fungal (candidiasis) or viral (herpes simplex-1 or cytomegalovirus) infections. In rare cases, it could be due to mycobacteria.^[19]

Unexplained chronic diarrhea in HIV infection is due to many possible causes, including common bacterial (Salmonella, Shigella, Listeria or Campylobacter) and parasitic infections; and uncommon opportunistic infections such as cryptosporidiosis, microsporidiosis, Mycobacterium avium complex (MAC) and viruses,^[20] astrovirus, adenovirus, rotavirus and cytomegalovirus, (the latter as a course of colitis).

In some cases, diarrhea may be a side effect of several drugs used to treat HIV, or it may simply accompany HIV infection, particularly during primary HIV infection. It may also be a side effect of antibiotics used to treat bacterial causes of diarrhea (common for Clostridium difficile). In the later stages of HIV infection, diarrhea is thought to be a reflection of changes in the way the intestinal tract absorbs nutrients, and may be an important component of HIV-related wasting.^[21]

Neurological and psychiatric[link]

HIV infection may lead to a variety of neuropsychiatric sequelae, either by infection of the now susceptible nervous system by organisms, or as a direct consequence of the illness itself.^[22]

Toxoplasmosis is a disease caused by the single-celled parasite called Toxoplasma gondii; it usually infects the brain, causing toxoplasma encephalitis, but it can also infect and cause disease in the eyes and lungs.^[23] Cryptococcal meningitis is an infection of the meninx (the membrane covering the brain and spinal cord) by the fungus Cryptococcus neoformans. It can cause fevers, headache, fatigue, nausea, and vomiting. Patients may also develop seizures and confusion; left untreated, it can be lethal.

Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease, in which the gradual destruction of the myelin sheath covering the axons of nerve cells impairs the transmission of nerve impulses. It is caused by a virus called JC virus which occurs in 70% of the population in latent form, causing disease only when the immune system has been severely weakened, as is the case for AIDS patients. It progresses rapidly, usually causing death within months of diagnosis.^[24]

AIDS dementia complex (ADC) is a metabolic encephalopathy induced by HIV infection and fueled by immune activation of HIV infected brain macrophages and microglia. These cells are productively infected by HIV and secrete neurotoxins of both host and viral origin.^[25] Specific neurological impairments are manifested by cognitive, behavioral, and motor abnormalities that occur after years of HIV infection and are associated with low CD4⁺ T cell levels and high plasma viral loads.

Prevalence is 10–20% in Western countries^[26] but only 1–2% of HIV infections in India.^[27][28] This difference is possibly due to the HIV subtype in India. AIDS related mania is sometimes seen in patients with advanced HIV illness; it presents with more irritability and cognitive impairment and less euphoria than a manic episode associated with true bipolar disorder. Unlike the latter condition, it may have a more chronic course. This syndrome is less frequently seen with the advent of multi-drug therapy.

Tumors[link]

Kaposi's sarcoma

People with HIV infections have substantially increased incidence of several cancers. This is primarily due to co-infection with an oncogenic DNA virus, especially Epstein-Barr virus (EBV), Kaposi's sarcoma-associated herpesvirus (KSHV) (also known as human herpesvirus-8 [HHV-8]), and human papillomavirus (HPV).^[29][30]

Kaposi's sarcoma (KS) is the most common tumor in HIV-infected patients. The appearance of this tumor in young homosexual men in 1981 was one of the first signals of the AIDS epidemic. Caused by a gammaherpes virus called Kaposi's sarcoma-associated herpes virus (KSHV), it often appears as purplish nodules on the skin, but can affect other organs, especially the mouth, gastrointestinal tract, and lungs. High-grade B cell lymphomas such as Burkitt's lymphoma, Burkitt's-like lymphoma, diffuse large B-cell lymphoma (DLBCL), and primary central nervous system lymphoma present more often in HIV-infected patients. These particular cancers often foreshadow a poor prognosis. Epstein-Barr virus (EBV) or KSHV cause many of these lymphomas. In HIV-infected patients, lymphoma often arises in extranodal sites such as the gastrointestinal tract.^[31] When they occur in an HIV-infected patient, KS and aggressive B cell lymphomas confer a diagnosis of AIDS.

Invasive cervical cancer in HIV-infected women is also considered AIDS-defining, it is caused by human papillomavirus (HPV).^[32]

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

Interestingly, the incidence of many common tumors, such as breast cancer or colon cancer, does not increase in HIV-infected patients. In areas where HAART is extensively used to treat AIDS, the incidence of many AIDS-related malignancies has decreased, but at the same time malignant cancers overall have become the most common cause of death of HIV-infected patients.^[33] In recent years, an increasing proportion of these deaths have been from non-AIDS-defining cancers.

Other infections[link]

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

Penicilliosis due to Penicillium marneffei is now the third most common opportunistic infection (after extrapulmonary tuberculosis and cryptococcosis) in HIV-positive individuals within the endemic area of Southeast Asia.^[34]

An infection that often goes unrecognized in people with AIDS is Parvovirus B19. Its main consequence is anemia, which is difficult to distinguish from the effects of antiretroviral drugs used to treat AIDS itself.^[35]

Virology[link]

Scanning electron micrograph of HIV-1, colored green, budding from a cultured lymphocyte.

AIDS is the ultimate clinical consequence of infection with HIV. HIV is a retrovirus that primarily infects vital organs of the human immune system such as CD4⁺ T cells (a subset of T cells), macrophages and dendritic cells. It directly and indirectly destroys CD4⁺ T cells.^[36]

Once the number of CD4⁺ T cells per microliter (µL) of blood drops below 200, cellular immunity is lost. Acute HIV infection usually progresses over time to clinical latent HIV infection and then to early symptomatic HIV infection and later to AIDS, which is identified either on the basis of the amount of CD4⁺ T cells remaining in the blood, and/or the presence of certain infections, as noted above.^[37]

In the absence of antiretroviral therapy, the median time of progression from HIV infection to AIDS is nine to ten years, and the median survival time after developing AIDS is only 9.2 months.^[38] However, the rate of clinical disease progression varies widely between individuals, from two weeks up to 20  years.

Many factors affect the rate of progression. These include factors that influence the body's ability to defend against HIV such as the infected person's general immune function.^[39][40] Older people have weaker immune systems, and therefore have a greater risk of rapid disease progression than younger people.

Poor access to health care and the existence of coexisting infections such as tuberculosis also may predispose people to faster disease progression.^[38][41][42] The infected person's genetic inheritance plays an important role and some people are resistant to certain strains of HIV. An example of this is people with the homozygous CCR5-Δ32 variation are resistant to infection with certain strains of HIV.^[43] HIV is genetically variable and exists as different strains, which cause different rates of clinical disease progression.^[44][45][46]

Transmission[link]

The three main transmission routes of HIV are sexual contact, exposure to infected body fluids or tissues, and from mother to fetus or child during the perinatal period. It is possible to find HIV in the saliva, tears, and urine of infected individuals, but there are no recorded cases of infection by these secretions, and the risk of infection is negligible.^[47]

Sexual transmission[link]

Sexual transmission occurs with the contact between sexual secretions of one person with the rectal, genital or oral mucous membranes of another. Unprotected sexual acts are riskier for the receptive partner than for the insertive partner, and the risk for transmitting HIV through unprotected anal intercourse is greater than the risk from vaginal intercourse or oral sex.

The majority of HIV infections are acquired through unprotected sexual relations between partners, one of whom has HIV. The primary mode of HIV infection worldwide is through sexual contact between members of the opposite sex.^[54][55][56]

However, oral sex is not entirely safe, as HIV can be transmitted through both insertive and receptive oral sex.^[57][58] Sexual assault greatly increases the risk of HIV transmission as condoms are rarely employed and physical trauma to the vagina or rectum occurs frequently, facilitating the transmission of HIV.^[59]

Other sexually transmitted infections (STI) increase the risk of HIV transmission and infection, because they cause the disruption of the normal epithelial barrier by genital ulceration and/or microulceration; and by accumulation of pools of HIV-susceptible or HIV-infected cells (lymphocytes and macrophages) in semen and vaginal secretions. Epidemiological studies from sub-Saharan Africa, Europe and North America suggest that genital ulcers, such as those caused by syphilis and/or chancroid, increase the risk of becoming infected with HIV by about fourfold. There is also a significant although lesser increase in risk from STIs such as gonorrhea, chlamydia and trichomoniasis, which all cause local accumulations of lymphocytes and macrophages.^[60]

Transmission of HIV depends on the infectiousness of the index case and the susceptibility of the uninfected partner. Infectivity seems to vary during the course of illness and is not constant between individuals. An undetectable plasma viral load does not necessarily indicate a low viral load in the seminal liquid or genital secretions. People who have been infected with one strain of HIV can still be infected later on in their lives by other strains.

Infection is unlikely in a single encounter. High rates of infection have been linked to a pattern of overlapping long-term sexual relationships. This allows the virus to quickly spread to multiple partners who in turn infect their partners. A pattern of serial monogamy or occasional casual encounters is associated with lower rates of infection.^[61]

Blood products[link]

CDC poster from 1989 highlighting the threat of AIDS associated with drug use

This transmission route is particularly relevant to intravenous drug users, hemophiliacs and recipients of blood transfusions and blood products. Sharing and reusing syringes contaminated with HIV-infected blood represents a major risk for infection with HIV.

Needle sharing is the cause of one third of all new HIV-infections in North America, China, and Eastern Europe. This route can also affect people who give and receive tattoos and piercings. Universal precautions are frequently not followed in both sub-Saharan Africa and much of Asia because of both a shortage of supplies and inadequate training.

The WHO estimates that approximately 2.5% of all HIV infections in sub-Saharan Africa are transmitted through unsafe healthcare injections.^[62] Because of this, the United Nations General Assembly has urged the nations of the world to implement precautions to prevent HIV transmission by health workers.^[63]

The risk of aquiring HIV from a blood blood transfusion is extremely low in developed countries where improved donor selection and HIV screening is performed. However, according to the WHO, the overwhelming majority of the world's population do not have access to safe blood and between 5% and 10% of the world's HIV infections come from transfusion of infected blood and blood products.^[64]

The risk of acquiring HIV from a needle stick from an HIV-infected person is about 0.3% (~1 in 333) and the risk post mucus membrane exposure to infected blood is 0.09% (~1:1000).^[50]

Perinatal transmission[link]

The transmission of the virus from the mother to the child can occur in utero during the last weeks of pregnancy and at childbirth. In the absence of treatment, the transmission rate between a mother and her child during pregnancy, labor and delivery is 25%.

However, when the mother takes antiretroviral therapy and gives birth by caesarean section, the rate of transmission is just 1%.^[49] The risk of infection is influenced by the viral load of the mother at birth, with the higher the viral load, the higher the risk. Breastfeeding also increases the risk of transmission by about 4 %.^[65]

No risk[link]

There is no risk of acquiring HIV if exposed to feces, nasal secretions, saliva, sputum, sweat, tears, urine, or vomit from an HIV infected person unless these are contaminated with blood.^[50]

Misconceptions[link]

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.^[66][67]

Pathophysiology[link]

The pathophysiology of AIDS is complex.^[68] Ultimately, HIV causes AIDS by depleting CD4⁺ T helper lymphocytes. This weakens the immune system and allows opportunistic infections. T lymphocytes 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.^[69]

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.^[70] The reason for the preferential loss of mucosal CD4⁺ T cells is that a majority of mucosal CD4⁺ T cells express the CCR5 coreceptor, whereas a small fraction of CD4⁺ T cells in the bloodstream do so.^[71]

HIV seeks out and destroys CCR5 expressing CD4⁺ cells during acute infection. A vigorous immune response eventually controls the infection and initiates the clinically latent phase. However, CD4⁺ T cells in mucosal tissues remain depleted throughout the infection, although enough remain to initially ward off life-threatening infections.

Continuous HIV replication results in a state of generalized immune activation persisting throughout the chronic phase.^[72] Immune activation, which is reflected by the increased activation state of immune cells and release of proinflammatory cytokines, results from the activity of several HIV gene products and the immune response to ongoing HIV replication. Another cause is the breakdown of the immune surveillance system of the mucosal barrier caused by the depletion of mucosal CD4⁺ T cells during the acute phase of disease.^[73]

This results in the systemic exposure of the immune system to microbial components of the gut’s normal flora, which in a healthy person is kept in check by the mucosal immune system. The activation and proliferation of T cells that results from immune activation provides fresh targets for HIV infection. However, direct killing by HIV alone cannot account for the observed depletion of CD4⁺ T cells since only 0.01–0.10% of CD4⁺ T cells in the blood are infected.

A major cause of CD4⁺ T cell loss appears to result from their heightened susceptibility to apoptosis when the immune system remains activated. Although new T cells are continuously produced by the thymus to replace the ones lost, the regenerative capacity of the thymus is slowly destroyed by direct infection of its thymocytes by HIV. Eventually, the minimal number of CD4⁺ T cells necessary to maintain a sufficient immune response is lost, leading to AIDS.

Diagnosis[link]

A generalized graph of the relationship between HIV copies (viral load) and CD4 counts over the average course of untreated HIV infection; any particular individual's disease course may vary considerably.                      CD4⁺ T Lymphocyte count (cells/mm³)                      HIV RNA copies per mL of plasma

The diagnosis of AIDS in a person infected with HIV is based on the presence of certain signs or symptoms. 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. However, clinical staging of patients was not an intended use for these systems as they are neither sensitive, nor specific. In developing countries, the World Health Organization's staging system for HIV infection and disease is used (using clinical and laboratory data), and in developed countries the CDC's classification system is used.

World Health Organization[link]

In 1990, the World Health Organization (WHO) grouped these infections and conditions together by introducing a staging system for people infected with HIV-1.^[74] An update took place in September 2005. Most of these conditions are opportunistic infections that are easily treatable in healthy people.

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

Center for Disease Control[link]

There are two main definitions for AIDS. The older definition is to referring to AIDS using the diseases that were associated with it, for example, lymphadenopathy, the disease after which the discoverers of HIV originally named the virus.^[75][76] In 1993, the CDC expanded their definition of AIDS to include all HIV positive people with a CD4⁺ T cell count below 200 per µL of blood or 14% of all lymphocytes.^[77] The majority of new AIDS cases in developed countries use either this definition or the pre-1993 CDC definition. 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.

HIV test[link]

Many people are unaware that they are infected with HIV.^[78] Less than 1% of the sexually active urban population in Africa has been tested, and this proportion is even lower in rural populations. Furthermore, only 0.5% of pregnant women attending urban health facilities are counseled, tested or receive their test results. Again, this proportion is even lower in rural health facilities.^[78] Therefore, donor blood and blood products used in medicine and medical research are screened for HIV.

HIV tests are usually performed on venous blood. Many laboratories use fourth generation screening tests which detect anti-HIV antibody (IgG and IgM) and the HIV p24 antigen. The detection of HIV antibody or antigen in a patient previously known to be negative is evidence of HIV infection. Individuals whose first specimen indicates evidence of HIV infection will have a repeat test on a second blood sample to confirm the results.

The window period (the time between initial infection and the development of detectable antibodies against the infection) can vary since it can take 3–6  months to seroconvert and to test positive. Detection of the virus using polymerase chain reaction (PCR) during the window period is possible, and evidence suggests that an infection may often be detected earlier than when using a fourth generation EIA screening test.

Positive results obtained by PCR are confirmed by antibody tests.^[79] Routinely used HIV tests for infection in neonates and infants (i. e., patients younger than 2 years),^[80] born to HIV-positive mothers, have no value because of the presence of maternal antibody to HIV in the child's blood. HIV infection can only be diagnosed by PCR, testing for HIV pro-viral DNA in the children's lymphocytes.^[81]

Prevention[link]

Know Aids – No Aids road sign in Spiti Valley, Himachel Pradesh, India, 2010

AIDS Clinic, McLeod Ganj, Himachel Pradesh, India, 2010

Sexual contact[link]

Consistent condom use reduces the risk of heterosexual HIV transmission by approximately 80% over the long-term.^[82] Where one partner of a couple is infected, consistent condom use results in rates of HIV infection for the uninfected person of below 1% per year.^[83] Some data supports the equivalence of female condoms to latex condoms however the evidence is not definitive.^[84] The use of the spermicide nonoxynol-9may increase the risk of transmission due to the fact that it causes vaginal and rectal irritation.^[85] A vaginal gel containing tenofovir, a reverse transcriptase inhibitor, when used immediately before sex, reduce infection rates by approximately 40% among Africa women.^[86]

Circumcision in sub-Saharan Africa reduces the risk of HIV infection in heterosexual men by 38 percent and 66 percent over two years.^[87] Based on these studies, the World Health Organizatio and UNAIDS both recommended male circumcision as a method of preventing female-to-male HIV transmission in 2007.^[88] Whether it protects against male-to-female transmission is disputed^[89][90] and whether it is of benefit in developed countries and among men who have sex with men is undetermined.^[91][92][93] Some experts fear that a lower perception of vulnerability among circumcised men may result in more sexual risk-taking behavior, thus negating its preventive effects.^[94] Women who have undergone female genital cutting have an increased risk of HIV.^[95]

Programs encouraging sexual abstinence do not appear to effect subsequent HIV risk.^[96] Evidence for a benefit from peer education is equally poor.^[97] Comprehensive sexual education provided at school may decrease high risk behavior.^[98] A substantial minority of young people continue to engage in high-risk practices despite HIV/AIDS knowledge, underestimating their own risk of becoming infected with HIV.^[99]

Pre exposure[link]

Early treatment of HIV-infected people with antiretrovirals protected 96% of partners from infection.^[100] 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, by couples where one is HIV positive, and by young heterosexuals in Africa.^[86]

Universal precautions within the health care environment are believed to be effective in decreasing the risk of HIV.^[101] 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.^[102]

Post exposure[link]

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.^[86] The use of the single agent zidovudine reduces the risk of subsequent HIV infection five fold.^[86] Current treatment regimes typical use lopinavir/ritonavir and lamivudine/zidovudine or emtricitabine/tenofovir and may decrease the risk further.^[86] The duration of treatment is usually four week^[103] and is associated with significant rates of adverse effects (for zidovudine ~70% including: nausea 24%, fatigue 22%, emotional distress 13%, headaches 9%).^[50]

Mother-to-child[link]

Programs to prevent the transmission of HIV from mothers to children can reduce rates of transmission by 92-99%.^[102][104] This primarily involves the use of a combination of antivirals during pregnancy and after birth in the infant but also potentially include bottle feeding rather than breastfeeding.^[105][104] If replacement feeding is acceptable, feasible, affordable, sustainable and safe mothers should avoid breast-feeding their infants however exclusive breast-feeding is recommended during the first months of life if this is not the case.^[106]

Vaccination[link]

As of 2012 there is no effective vaccine for HIV or AIDS.^[107] A single trial of the vaccine RV 144 published in 2009 found a partial efficacy rate of ~30% and has stimulated optimism in the research community regarding developing a truly effective vaccine.^[108] Further trials of the vaccine are ongoing.^[109][110]

Management[link]

There is currently no effective HIV vaccine or cure for HIV/AIDS. Treatment with antiretroviral medications slows progression of the disease^[111] and as of 2010 more than 6.6 million people were taking them.^[7]

Antiviral therapy[link]

Abacavir – a nucleoside analog reverse transcriptase inhibitor (NARTI or NRTI)

The chemical structure of Abacavir

Current treatment for HIV infection consists of highly active antiretroviral therapy, or HAART which is recommended when CD4 counts are below 350 per microL.^[112] Traditionally, treatment has been recommended for people without symptoms when CD4 cell counts fall to 200–250 cells per microliter of blood. However, beginning treatment earlier (at a CD4 level of 350 cells/microliter) may significantly reduce the risk of death.^[113] HAART is thought to increase survival time by between 4 and 12  years.^[114][115] This has been highly beneficial to many HIV-infected individuals since its introduction in 1996 when the protease inhibitor-based HAART initially became available.^[4] Current optimal HAART options consist of combinations (or "cocktails") consisting of at least three drugs belonging to at least two types, or "classes, " of antiretroviral agents.

Typical regimens consist of two nucleoside analogue reverse transcriptase inhibitors (NARTIs or NRTIs) plus either a protease inhibitor or a non-nucleoside reverse transcriptase inhibitor (NNRTI). Because HIV disease progression in children is more rapid than in adults, and laboratory parameters are less predictive of risk for disease progression, particularly for young infants, treatment recommendations are more aggressive for children than for adults.^[116] In developed countries where HAART is available, the viral load, CD4 counts, rapidity of CD4 decline and patient readiness help determine when to recommend initiating treatment.^[117]

Many HIV-infected individuals have experienced improvements in their general health and quality of life, which has led to a decrease of HIV-associated morbidity and mortality.^[118][119]

For some people, which can be more than fifty percent, HAART achieves far less than optimal results, due to medication intolerance/side effects, prior ineffective antiretroviral therapy and infection with a drug-resistant strain of HIV. Non-adherence and non-persistence with therapy are the major reasons why some people do not benefit from HAART.^[120] The reasons for non-adherence and non-persistence are varied. Major psychosocial issues include poor access to medical care, inadequate social supports, psychiatric disease and drug abuse. HAART regimens can also be complex and thus hard to follow, with large numbers of pills taken frequently.^{[121][122][123]}

Side effects can also deter people from persisting with HAART, these include lipodystrophy, dyslipidaemia, diarrhoea, insulin resistance, an increase in cardiovascular risks and birth defects.^[124] Anti-retroviral drugs are expensive, and the majority of the world's infected individuals do not have access to medications and treatments for HIV and AIDS. However, the costs of anti-retroviral drugs have fallen recently in low-income countries. Moreover, patients' quality of life indices benefit from anti-retroviral treatment especially if healthcare services are adequate.^[125] In the absence of a cure for AIDS, anti-retroviral treatment is likely to be a cost-effective strategy for enhancing well-being of AIDS patients and their dependents.

Alternative medicine[link]

In the US, approximately 60% of people with HIV use various forms of complementary or alternative medicine.^[126] The effectiveness of most of these therapies however has not been established.^[127] With respect to dietary advice and AIDS some evidence has shown a benefit from micronutrient supplements.^[128] Evidence for supplementation with selenium is mixed with some tentative evidence of benefit.^[129] There is some evidence that vitamin A supplementation in children reduces mortality and improves growth.^[130] In Africa in nutritionally compromised pregnant and lactating women a multivitamin supplementation improved outcomes for both mothers and children.^[130] Dietary intake of micronutrients at RDA levels by HIV-infected adults is recommended by the World Health Organization. ^{[131] [132]} The WHO further states that several studies indicate that supplementation of vitamin A, zinc, and iron can produce adverse effects in HIV positive adults.^[132] In 2005 there was not enough evidence to support the use of herbal medicines.^[133]

Prognosis[link]

Disability-adjusted life year for HIV and AIDS per 100,000  inhabitants as of 2004.

no data   ≤ 10   10–25   25–50   50–100   100–500   500–1000

1000–2500   2500–5000   5000–7500   7500-10000   10000-50000   ≥ 50000

Without treatment, the median survival time after infection with HIV is estimated to be 9 to 11 years, depending on the HIV subtype,^[134] and the median survival rate after diagnosis of AIDS in resource-limited settings where treatment is not available ranges between 6 and 19 months.^[135] HAART reduces the death rate from this disease by 80%, and raised the life expectancy for a newly diagnosed HIV-infected person to about 20 years.^[136]

As new treatments continue to be developed and because HIV continues to evolve resistance to treatments, estimates of survival time are likely to continue to change. Without antiretroviral therapy, death normally occurs within a year after the individual progresses to AIDS.^[38] Most patients die from opportunistic infections or malignancies associated with the progressive failure of the immune system.^[137] The rate of clinical disease progression varies widely between individuals and has been shown to be affected by many factors such as host susceptibility and immune function^[39][40][43] health care and co-infections,^[38][137] as well as which particular strain of the virus is involved.^[45]

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 always clear whether these conditions result from the infection, related complications, or are side effects of treatment.^{[138][139][140][29][30][141][124][142]}

The largest cause of AIDS morbidity today, globally, is tuberculosis co-infection. In Africa, HIV is the single most important factor contributing to the increase in the incidence of TB since 1990.^[143] Life expectancy has fallen in the worst-affected countries; for example, in 2006 it was estimated that it had dropped from 65 to 35 years in Botswana.^[5]

Epidemiology[link]

Estimated prevalence of HIV among young adults (15–49) per country at the end of 2005.

HIV infections are considered pandemic by the World Health Organization (WHO).^[144] As of 2010 approximately 34 million people have HIV globally.^[7] Other these approximately 16.8 million are women and 3.4 million are less than 15 years old.^[7] It results in about 1.8 million death in 2010 down from 3.1 million in 2001.^[7]

Sub-Saharan Africa is the region most effected. In 2010, an estimated 68% (22.9 million) of all HIV cases and 66% of all deaths (1.2 million) occurred in this region.^[145] This means that about 5% of the adult populations is infected.^[146] Here in contrast to other regions women compose nearly 60% of cases.^[145] South Africa has the largest population of people with HIV of any country in the world at 5.9 million.^[145]

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.^[146] Approximately 2.4 million of these cases are in India.^[145] Prevalence is lowest in Western and Central Europe at 0.2% and East Asia at 0.1%.^[146]

In 2008 approximately 1.2 million people have HIV in the United States of which 20% do not realize that they are infected.^[147] It resulted in about 17,500 deaths.^[147] In the United Kingdom as of 2009 there where approximately 86,500 cases which resulted in 516 deaths.^[148] In Canada as of 2008 there where about 65,000 cases which results in 53 deaths.^[149] Since AIDS was first recognized in 1981 and 2009 it has led to nearly 30 million deaths.^[8]

History[link]

AIDS was first reported June 5, 1981, when the CDC recorded a cluster of Pneumocystis carinii pneumonia (now still classified as PCP but known to be caused by Pneumocystis jirovecii) in five homosexual men in Los Angeles.^[150] In the beginning, the CDC did not have an official name for the disease, often referring to it by way of the diseases that were associated with it, for example, lymphadenopathy, the disease after which the discoverers of HIV originally named the virus.^[75][76] They also used Kaposi's Sarcoma and Opportunistic Infections, the name by which a task force had been set up in 1981.^[151]

In the general press, the term GRID, which stood for gay-related immune deficiency, had been coined.^[152] The CDC, in search of a name, and looking at the infected communities coined “the 4H disease, ” as it seemed to single out Haitians, homosexuals, hemophiliacs, and heroin users.^[153] However, after determining that AIDS was not isolated to the gay community,^[151] the term GRID became misleading and AIDS was introduced at a meeting in July 1982.^[154] By September 1982 the CDC started using the name AIDS, and properly defined the illness.^[155]

The earliest known positive identification of the HIV-1 virus comes from the Congo in 1959 and 1960 though genetic studies indicate that it passed into the human population from chimpanzees around fifty years earlier.^[10] A 2007 study states that a strain of HIV-1 probably moved from Africa to Haiti and then entered the United States around 1969.^[156]

HIV descends from the related simian immunodeficiency virus (SIV), which infects apes and monkeys in Africa. There is evidence that humans who participate in bushmeat activities, either as hunters or as bushmeat vendors, commonly acquire SIV.^[157] However, only a few of these infections were able to cause epidemics in humans, and all did so in the late 19th—early 20th century. To explain why HIV became epidemic only by that time, there are several theories, each invoking specific driving factors that may have promoted SIV adaptation to humans, or initial spread: social changes following colonialism,^[158] rapid transmission of SIV through unsafe or unsterile injections (that is, injections in which the needle is reused without being sterilised),^[159] colonial abuses and unsafe smallpox vaccinations or injections,^[160] or prostitution and the concomitant high frequency of genital ulcer diseases (such as syphilis) in nascent colonial cities.^[161][162] See the main article Origin of AIDS.

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. It had been diagnosed during 1984.^[163] A notable British casualty of AIDS that year was Nicholas Eden, a gay Member of Parliament and son of the late prime minister Anthony Eden.^[164][165] The virus claimed perhaps its most famous victim yet on November 24, 1991, when British rock star Freddie Mercury, lead singer of the band Queen, died from an AIDS related illness having only announced that he was suffering from the illness the previous day.^[166] However he had been diagnosed as HIV positive during 1987.^[167] One of the first high profile heterosexual victims of the virus was Arthur Ashe, the American tennis player. He was diagnosed as HIV positive on 31 August 1988, having contracted the virus from blood transfusions during heart surgery earlier in the 1980s. Further tests within 24 hours of the initial diagnosis revealed that Ashe had AIDS, but he did not tell the public about his diagnosis until April 1992.^[168] He died, aged 49, as a result of the AIDS virus on 6 February 1993.^[169]

A more controversial theory known as the OPV AIDS hypothesis suggests that the AIDS epidemic was inadvertently started in the late 1950s in the Belgian Congo by Hilary Koprowski's research into a poliomyelitis vaccine.^[170][171] According to scientific consensus, the available evidence does not support this scenario.^{[172][173][174]}

Society and culture[link]

Stigma[link]

Ryan White became a poster child for HIV after being expelled from school because of his infection.

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.^[175] 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.^[176]

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.^[177]

• Symbolic AIDS stigma—the use of HIV/AIDS to express attitudes toward the social groups or lifestyles perceived to be associated with the disease.^[177]
• Courtesy AIDS stigma—stigmatization of people connected to the issue of HIV/AIDS or HIV- positive people.^[178]

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 attitudes.^[179] There is also a perceived association between AIDS and all male-male sexual behavior, including sex between uninfected men.^[177]

Economic impact[link]

Changes in life expectancy in some hard-hit African countries.                      Botswana                     Zimbabwe                     Kenya                     South Africa                     Uganda

HIV and AIDS affects economic growth by reducing the availability of human capital.^[180] Without proper nutrition, health care and medicine that is available in developed countries, large numbers of people suffer and die from AIDS-related complications. They will not only be unable to work, but will also require significant medical care. The forecast is that this will probably cause a collapse of economies and societies in countries with a significant AIDS population. In some heavily infected areas, the epidemic has left behind many orphans cared for by elderly grandparents.^[181]

The increased mortality has results in a smaller skilled population and labor force. This smaller labor force consists of increasingly younger people, with reduced knowledge and work experience leading to reduced productivity. An increase in workers’ time off to look after sick family members or for sick leave lowers productivity. Increased mortality reduces the mechanisms that generate human capital and investment in people, through loss of income and the death of parents.

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 results in 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.^[181]

On the level of the household, AIDS results in both the loss of income and increased spending on healthcare by the household. The income effects of this lead to spending reduction as well as a substitution effect away from education and towards healthcare and funeral spending. A study in Côte d'Ivoire showed that households with an HIV/AIDS patient spent twice as much on medical expenses as other households.^[182]

Religion and AIDS[link]

The topic of religion and AIDS has become highly controversial in the past twenty years, primarily because many prominent religious leaders have publicly declared their opposition to the use of condoms,^{[183][184][Full citation needed]} which scientists feel is currently the only means of stopping the epidemic.^{[citation needed]} However, there is a growing openness to faith-based methods due to the failure rates associated with condoms.^[184] Other issues involve religious participation in global health care services^{[citation needed]} and collaboration with secular organizations such as UNAIDS and the World Health Organization.^{[citation needed]}

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.^[184]

In addition to prevention, some religious groups have interrupted the treatment of AIDS. According to the African Health Policy Network, some churches in London claim that prayer will cure AIDS and the Hackney-based Centre for the Study of Sexual Health and HIV reports that several people have stopped taking their medication, sometimes on the direct advice of their pastor, leading to a number of deaths.^[185] 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,^[185] and US patent application 2001051133 similarly suggests that intravenous pure distilled water will eradicate HIV through the mercy of God.^[186]

Denialism and conspiracy theories[link]

A small group of individuals continue to dispute the connection between HIV and AIDS,^[187] the existence of HIV itself, or the validity of HIV testing and treatment methods.^[188][189] These claims, known as AIDS denialism, have been examined and rejected by the scientific community.^[190] However, they have had a significant political impact, particularly in South Africa, where the government's official embrace of AIDS denialism 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.^{[191][192][193]}

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.^[194]

Research[link]

It has been postulated that only a vaccine can halt the pandemic because a vaccine would possibly cost less, thus being affordable for developing countries, and would not require daily treatments. However, even after almost 30 years of research, HIV-1 remains a difficult target for a vaccine.^[195]

Research to improve current treatments includes decreasing side effects of current drugs, further simplifying drug regimens to improve adherence, and determining the best sequence of regimens to manage drug resistance. A number of studies have shown that measures to prevent opportunistic infections can be beneficial when treating patients with HIV infection or AIDS. Vaccination against hepatitis A and B is advised for patients who are not infected with these viruses and are at risk of becoming infected.^[196] Patients with substantial immunosuppression are also advised to receive prophylactic therapy for Pneumocystis jiroveci pneumonia (PCP), and many patients may benefit from prophylactic therapy for toxoplasmosis and Cryptococcus meningitis as well.^[197]

Researchers have discovered an abzyme that can destroy the protein gp120 CD4 binding site. This protein is common to all HIV variants as it is the attachment point for B lymphocytes and subsequent compromising of the immune system.^[198]

Researchers from the Hebrew University of Jerusalem have also discovered that a combination of peptides that stimulate integration together with the protease inhibitor Ro 31-8959 caused apoptotic cell death of HIV-infected cells with total extermination of the virus but did not harm healthy cells.^[199][200] It could take several years before a commercial treatment based on this discovery becomes available.^[201]

Reactivation of the retrocyclin pseudogene has been proposed as a possible prevention method, as was demonstrated in a proof-of-concept study in tissue culture cells.^[202]

Stem cell transplantation[link]

In Berlin, Germany, a 42-year-old leukemia patient, Timothy Ray Brown (also referred to as the "Berlin Patient"),^[203] infected with HIV for more than a decade was given an experimental transplant of bone marrow with cells that contained an unusual natural variant of the CCR5 cell-surface receptor by a team around Gero Hütter. This CCR5-Δ32 variant has been shown to make some cells from people who are born with it resistant to infection with some strains of HIV. Almost two years after the transplant, and even after the patient reportedly stopped taking antiretroviral medications, HIV has not been detected in the patient's blood.^[204] As of December 2010, three years after the transplant, Brown was still free of any detectable HIV in his blood and was described, in a paper in the journal Blood, as "cured".^[203][205]

Notes[link]