(AIDS or Aids) is a collection of symptoms and infections in humans resulting from the specific damage to the immune system caused by infection with the human immunodeficiency virus (HIV),^[1] the late stage of which leaves individuals prone to opportunistic infections and tumors. Although treatments for AIDS and HIV exist to slow the virus's progression, there is no known cure.

HIV is transmitted through direct contact of a mucous membrane or the bloodstream with a bodily fluid containing HIV, such as blood, semen, vaginal fluid, preseminal fluid, and breast milk.^[2][3] This transmission can come in the form of: (anal, vaginal or oral) sex; blood transfusion; contaminated needles; exchange between mother and infant during pregnancy, childbirth, or breastfeeding; or other exposure to one of the above bodily fluids.

Most researchers believe that HIV originated in sub-Saharan Africa during the twentieth century;^[4] it is now a pandemic, with an estimated 38.6 million people now living with the disease worldwide.^[5] As of January 2006, the Joint United Nations Programme on HIV/AIDS (UNAIDS) and the World Health Organization (WHO) estimate that AIDS has killed more than 25 million people since it was first recognized on December 1, 1981, making it one of the most destructive epidemics in recorded history, so much so that it has been called a pandemic. In 2005 alone, AIDS claimed an estimated 2.4 - 3.3 million lives, of which more than 570,000 were children.^[5] A third of these deaths are occurring in sub-Saharan Africa, retarding economic growth by destroying human capital. Antiretroviral treatment reduces both the mortality and the morbidity of HIV infection, but routine access to antiretroviral medication is not available in all countries.^[6] HIV/AIDS stigma is more severe than that associated with other life-threatening conditions and extends beyond the disease itself to providers and even volunteers involved with the care of people living with HIV.

Infection by HIV

For more details on this topic, see HIV.

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

AIDS is the most severe manifestation of infection with HIV. HIV is a retrovirus that primarily infects vital components of the human immune system such as CD4+ T cells, macrophages and dendritic cells. It directly and indirectly destroys CD4+ T cells. CD4+ T cells are required for the proper functioning of the immune system. When HIV kills CD4+ T cells so that there are less than 200 CD4+ T cells per µl blood, cellular immunity is lost, leading to AIDS. Acute HIV infection progresses over time to clinical latent HIV infection and then to early symptomatic HIV infection and later, to AIDS, which is identified on the basis of the amount of CD4+ T cells in the blood and the presence of certain infections.

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.^[7] However, the rate of clinical disease progression varies widely between individuals, from two weeks up to 20 years. Many factors affect the rate of progression. These include factors that influence the body's ability to defend against HIV such as the infected person's general immune function.^[8][9] Older people have weaker immune systems so they have a greater risk of faster disease progression than younger people. Poor access to health care and the existence of coexisting infections such as tuberculosis may predispose to faster disease progression.^[7][10][11] The infected person's genetic inheritance plays an important role and some people are resistant to certain strains of HIV.^[12] An example of this is people with the CCR5-Δ32 mutation; these people are resistant to infection with certain strains of HIV. The strain of HIV that infects someone plays a role in the disease progression rate. HIV is genetically variable and exists as different strains which cause different rates of clinical disease progression.^[13][14][15] The use of highly active antiretroviral therapy prolongs both the median time of progression to AIDS and the median survival time.

Diagnosis

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 (WHO) staging system for HIV infection and disease, using clinical and laboratory data, is used and in developed countries, the Centers for Disease Control (CDC) Classification System is used.

WHO disease staging system for HIV infection and disease

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

In 1990, the World Health Organization (WHO) grouped these infections and conditions together by introducing a staging system for patients infected with HIV-1.^[16] An update took place in September 2005. Most of these conditions are opportunistic infections that are easily treatable in healthy people.

Stage I: HIV disease 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.

CDC classification system for HIV infection

Main article: CDC Classification System for HIV Infection

The Centers for Disease Control and Prevention (CDC) originally classified AIDS as GRID which stood for Gay Related Immune Disease. However, after determining that AIDS is not isolated to homosexual people the name was changed to the neutral AIDS. In 1993, the CDC expanded their definition of AIDS to include healthy HIV positive people with a CD4+ T cell count of less than 200 per µl of blood. The majority of new AIDS cases in developed countries use this definition.^[17] 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

Main article: HIV test

Approximately half of those infected with HIV do not know their HIV status until an AIDS diagnosis is made with an HIV test. Donor blood and blood products used in medicine and medical research are screened for HIV using such a test. Typical HIV tests, including the HIV enzyme immunoassay and the Western blot assay, detect HIV antibodies in serum, plasma, oral fluid, dried blood spot or urine of patients. However, the window period (the time between initial infection and the development of detectable antibodies against the infection) can vary. This is why it can take 6-12 months to seroconvert and test positive. Commercially available tests to detect other HIV antigens, HIV-RNA, and HIV-DNA in order to detect HIV infection prior to the development of detectable antibodies are available. However, for the diagnosis of HIV infection these assays are not specifically approved, but are nonetheless routinely used in developed countries.

Symptoms and complications

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.

The symptoms of AIDS are primarily the result of conditions that do not normally develop in individuals with healthy immune systems. Most of these conditions are infections caused by bacteria, viruses, fungi and parasites that are normally controlled by the elements of the immune system that HIV damages. Opportunistic infections are common in people with AIDS.^[18] HIV affects nearly every organ system. People with AIDS also have an increased risk of developing various cancers such as Kaposi sarcoma, cervical cancer and cancers of the immune system known as lymphomas.

Additionally, people with AIDS often have systemic symptoms of infection like fevers, sweats (particularly at night), swollen glands, chills, weakness, and weight loss.^[19][20] After the diagnosis of AIDS is made, the current average survival time with antiretroviral therapy is estimated to be now more than 5 years,^[21] but because new treatments continue to be developed and because HIV continues to evolve resistance to treatments, estimates of survival time are likely to continue to change. Without antiretroviral therapy, death normally occurs within a year.^[7] Most patients die from opportunistic infections or malignancies associated with the progressive failure of the immune system.^[22]

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^[8][9][12] health care and co-infections,^[7][22] as well as factors relating to the viral strain.^[14][23][24] 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.

Major pulmonary illnesses

• Pneumocystis jiroveci pneumonia (originally known as Pneumocystis carinii pneumonia, often-abbreviated PCP) is relatively rare in healthy, immunocompetent people but common among HIV-infected individuals. 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 per µl.^[25]
• Tuberculosis (TB) is unique among infections associated with HIV because it is transmissible to immunocompetent people via the respiratory route, is easily treatable once identified, may occur in early-stage HIV disease, and is preventable with drug therapy. However, multi-drug resistance is a potentially serious problem. Even though its incidence has declined because of the use of directly observed therapy and other improved practices in Western countries, this is not the case in developing countries where HIV is most prevalent. In early-stage HIV infection (CD4 count >300 cells per µl), TB typically presents as a pulmonary disease. In advanced HIV infection, TB often presents atypically with extrapulmonary 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.^[26] Alternatively, symptoms may relate more to the site of extrapulmonary involvement.

Major gastro-intestinal illnesses

• 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.^[27]
• Unexplained chronic diarrhea in HIV infection is due to many possible causes, including common bacterial (Salmonella, Shigella, Listeria, Campylobacter, or Escherichia coli) and parasitic infections, and uncommon opportunistic infections such as cryptosporidiosis, microsporidiosis, Mycobacterium avium complex (MAC) and cytomegalovirus (CMV) colitis. 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.^[28]

Major neurological illnesses

• Toxoplasmosis is a disease caused by the single-celled parasite called Toxoplasma gondii; it usually infects the brain causing toxoplasma encephalitis but it can infect and cause disease in the eyes and lungs.^[29]
• 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.^[30]
• AIDS dementia complex (ADC) is a metabolic encephalopathy induced by HIV infection and fuelled by immune activation of HIV infected brain macrophages and microglia which secrete neurotoxins of both host and viral origin.^[31] Specific neurological impairments are manifested by cognitive, behavioral, and motor abnormalities that occur after years of HIV infection and is associated with low CD4+ T cell levels and high plasma viral loads. Prevalence is 10-20% in Western countries^[32] but only 1-2% of HIV infections in India.^[33][34] This difference is possibly due to the HIV subtype in India.
• 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.

Major HIV-associated malignancies

Patients with HIV infection have substantially increased incidence of several malignant cancers. This is primarily due to co-infection with an oncogenic DNA virus, especially Epstein-Barr virus (EBV), Kaposi's sarcoma-associated herpesvirus (KSHV), and human papillomavirus (HPV).^[35][36] The following confer a diagnosis of AIDS when they occur in an HIV-infected person.

• 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, and diffuse large B-cell lymphoma (DLBCL), present more often in HIV-infected patients. These particular cancers often foreshadow a poor prognosis. In some cases these lymphomas are AIDS-defining. Epstein-Barr virus (EBV) or KSHV cause many of these lymphomas.
• Cervical cancer in HIV-infected women is considered AIDS-defining. It is caused by human papillomavirus (HPV).

In addition to the AIDS-defining tumors listed above, HIV-infected patients are at increased risk of certain other tumors, such as Hodgkin's disease and anal and rectal carcinomas. However, the incidence of many common tumors, such as breast cancer or colon cancer, 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.^[37]

Other opportunistic infections

AIDS patients often develop opportunistic infections that present with non-specific symptoms, especially low-grade fevers and weight loss. These include infection with Mycobacterium avium-intracellulare and cytomegalovirus (CMV). CMV can 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.^[38]

Transmission and prevention

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 perinatal period. It is possible to find HIV in the saliva, tears, and urine of infected individuals, but due to the low concentration of virus in these biological liquids, the risk is negligible.

Sexual contact

The majority of HIV infections are acquired through unprotected sexual relations between partners, one of whom has HIV. Sexual transmission occurs with the contact between sexual secretions of one partner with the rectal, genital or oral mucous membranes of another. Unprotected receptive sexual acts are riskier than unprotected insertive sexual acts, with the risk for transmitting HIV from an infected partner to an uninfected partner through unprotected insertive anal intercourse greater than the risk for transmission through vaginal intercourse or oral sex. Oral sex is not without its risks as HIV is transmissible through both insertive and receptive oral sex.^[47] The risk of HIV transmission from exposure to saliva is considerably smaller than the risk from exposure to semen; contrary to popular belief, one would have to swallow gallons of saliva from a carrier to become infected.^[48]

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 have suggested that there is approximately a four times greater risk of becoming infected with HIV in the presence of a genital ulcer such as those caused by syphilis and/or chancroid. There is also a significant though lesser increased risk in the presence of STDs such as gonorrhea, Chlamydial infection and trichomoniasis which cause local accumulations of lymphocytes and macrophages.^[49]

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. Each 10-fold increment of seminal HIV RNA is associated with an 81% increased rate of HIV transmission.^[49][50] Women are more susceptible to HIV-1 infection due to hormonal changes, vaginal microbial ecology and physiology, and a higher prevalence of sexually transmitted diseases.^[51][52] People who are infected with HIV can still be infected by other, more virulent strains.

During a sexual act, only male or female condoms can reduce the chances of infection with HIV and other STDs and the chances of becoming pregnant. The best evidence to date indicates that condom use reduces the risk of heterosexual HIV transmission by approximately 80%.^[53] The effective use of condoms and screening of blood transfusion in North America, Western and Central Europe is cr ed with the low rates of AIDS in these regions.

Promoting condom use, however, has often proved controversial and difficult. Many religious groups, most visibly the Catholic Church, have opposed the use of condoms on religious grounds, and have sometimes seen condom promotion as an affront to the promotion of marriage, monogamy and sexual morality. This attitude is found among some health care providers and policy makers in sub-Saharan African nations, where HIV and AIDS prevalence is extremely high.^[54] They also believe that the distribution and promotion of condoms is tantamount to promoting sex amongst the youth and sending the wrong message to uninfected individuals. However, no evidence has been produced that promotion of condom use increases sexual promiscuity. However, Pope Benedict XVI commissioned a report on whether it might be acceptable for Catholics to use condoms in to protect life inside a marriage when one partner is infected with HIV, or is sick with AIDS.^[55] Other religious groups, such as the Scottish Episcopalians, have argued that preventing HIV infection is a moral task in itself and that condoms are therefore acceptable or even praiseworthy from a religious point of view.

The male latex condom, if used correctly without oil-based lubricants, is the single most efficient available technology to reduce the sexual transmission of HIV and other sexually transmitted infections. Manufacturers recommend that oil-based lubricants such as petroleum jelly, butter, and lard not be used with latex condoms as they weaken the latex, making the condoms porous. If necessary, manufacturers recommend using water-based lubricants. Oil-based lubricants can however be used with polyurethane condoms.^[56] Latex degrades over time, making them porous, which is why condoms have expiration dates. In Europe and the United States, condoms have to conform to European (EC 600) or American (D3492) standards to be considered protective against HIV transmission.

The female condom is an alternative to the male condom and is made from polyurethane, which allows it to be used in the presence of oil-based lubricants. They are larger than male condoms and have a stiffened ring-shaped opening, and are designed to be inserted into the vagina. The female condom contains an inner ring, which keeps the condom in place inside the vagina – inserting the female condom requires squeezing this ring.

With consistent and correct use of condoms, there is a very low risk of HIV infection. Studies on couples where one partner is infected show that with consistent condom use, HIV infection rates for the uninfected partner are below 1% per year.^[57]

The United States government and health organizations both endorse the ABC Approach to lower the risk of acquiring AIDS during sex:

Abstinence or delay of sexual activity, especially for youth,

Being faithful, especially for those in committed relationships,

Condom use, for those who engage in risky behavior.

This approach has been very successful in Uganda, where HIV prevalence has decreased from 15% to 5%. However, more has been done than implementing the ABC Approach as Edward Green, a Harvard medical anthropologist put it, "Uganda has pioneered approaches towards reducing stigma, bringing discussion of sexual behavior out into the open, involving HIV-infected people in public education, persuading individuals and couples to be tested and counseled, improving the status of women, involving religious organizations, enlisting traditional healers, and much more." There is no conclusive proof that abstinence-only programs have been successful in any country in the world in changing sexual behavior or in reducing HIV transmission.^[58] Instead, evaluations of several abstinence-only programs in the US showed a negative impact on the willingness of youths to use contraceptives, due to the emphasis on contraceptives' failure rates.^[59] Still, condom use is heavily promoted by other programs and initiatives. Condom use is an integral part of the CNN Approach. This is:

Condom use, for those who engage in risky behavior,