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AIDS

 

Acquired immune deficiency syndrome or acquired immunodeficiency syndrome (AIDS) is a disease of the human immune system caused by the human immunodeficiency virus (HIV).


This condition progressively reduces the effectiveness of the immune system and leaves individuals susceptible to opportunistic infections and tumors. 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.


This transmission can involve anal, vaginal or oral sex,blood transfusion, contaminated hypodermic needles, exchange between mother and baby during pregnancy,childbirth, breastfeeding or other exposure to one of the above bodily fluids.


AIDS is now a pandemic. In 2007, it was estimated that 33.2 million people lived with the disease worldwide, and that AIDS killed an estimated 2.1 million people, including 330,000 children. Over three-quarters of these deaths occurred in sub-Saharan Africa,retarding economic growth and destroying human capital.


Genetic research indicates that HIV originated in west-central Africa during the late nineteenth or early twentieth century. AIDS was first recognized by the U.S. Centers for Disease Control and Prevention in 1981 and its cause, HIV, identified in the early 1980s.


Although treatments for AIDS and HIV can slow the course of the disease, there is currently no vaccine or cure. Antiretroviral treatment reduces both the mortality and the morbidity of HIV infection, but these drugs are expensive and routine access to antiretroviral medication is not available in all countries. 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 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. 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. 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.


Other infections

AIDS patients 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.


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

Symptoms


  • Diarrhoea
  • Fatigue
  • Fever
  • Frequent Vaginal Yeast Infections
  • Headache
  • Mouth sores, including fungal (candida) infection
  • Muscular stiffness or aching
  • Rash of various types, including seborrheic dermatitis
  • Sore throat
  • Swollen lymph glands

 

Causes

AIDS is the most severe acceleration 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.


Once HIV has killed so many CD4+ T cells that there are fewer than 200 of these cells per microliter (µL) of blood, cellular immunity is lost. 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 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.


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. 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. 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. 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.  HIV is genetically variable and exists as different strains, which cause different rates of clinical disease progression.


Sexual transmission

Sexual transmission occurs with the contact between sexual secretions of one person with the rectal, genital or oral mucous membranes of another. Unprotected receptive sexual acts are riskier than unprotected insertive sexual acts, and the risk for transmitting HIV through unprotected anal intercourse is greater than the risk from vaginal intercourse or oral sex. However, oral sex is not entirely safe, as HIV can be transmitted through both insertive and receptive oral sex. 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.


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.


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.


However, each 10-fold increase in the level of HIV in the blood is associated with an 81% increased rate of HIV transmission. 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.


People who have been infected with one strain of HIV can still be infected later on in their lives by other, more virulent 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.


HIV spreads readily through heterosexual sex in Africa, but less so elsewhere. One possibility being researched is that schistosomiasis, which affects up to 50% of women in parts of Africa, damages the lining of the vagina.

Exposure to blood-borne pathogens

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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. The risk of being infected with HIV from a single prick with a needle that has been used on an HIV-infected person is thought to be about 1 in 150 (see table above). Post-exposure prophylaxis with anti-HIV drugs can further reduce this risk.

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. 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.

The risk of transmitting HIV to blood transfusion recipients 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 does 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.

Prenatal transmission

The transmission of the virus from the mother to the child can occur in utero during the last weeks of pregnancy and at childbirth. 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%. 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 %.

Misconceptions

A number of misconceptions have arisen surrounding HIV/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 gay men can lead to AIDS infection, and that open discussion of homosexuality and HIV in schools will lead to increased rates of homosexuality and AIDS.

Diagnosis

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

WHO disease staging system

In 1990, the World Health Organization (WHO) grouped these infections and conditions together by introducing a staging system for patients infected with HIV-1.  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 diarrhoea 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

There are two main definitions for AIDS, both produced by the Centers for Disease Control and Prevention (CDC). 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. 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. 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

Many people are unaware that they are infected with HIV.  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. Therefore,  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. Routinely used HIV tests for infection in neonates and infants (i.e. patients younger than 2 years), 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.

Prevention

The three main transmission routes of HIV are sexual contact, exposure to infected body fluids or tissues and from mother to foetus or child during prenatal 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.

Sexual contact

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.

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 typical condom use reduces the risk of heterosexual HIV transmission by approximately 80% over the long-term, though the benefit is likely to be higher if condoms are used correctly on every occasion.

The male latex condom, if used correctly without oil-based lubricants, is the single most effective 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, because they dissolve the latex, making the condoms porous. If necessary, manufacturers recommend using water-based lubricants.

Oil-based lubricants can however be used with polyurethane condoms.

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. However, at present availability of female condoms is very low and the price remains prohibitive for many women.

Preliminary studies suggest that, where female condoms are available, overall protected sexual acts increase relative to unprotected sexual acts, making them an important HIV prevention strategy.

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. Prevention strategies are well-known in developed countries, but epidemiological and behavioral studies in Europe and North America suggest that 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.

Randomized controlled trials have shown that male circumcision lowers the risk of HIV infection among heterosexual men by up to 60%. It is expected that this procedure will be actively promoted in many of the countries affected by HIV, although doing so will involve confronting a number of practical, cultural and attitudinal issues. However, programs to encourage condom use, including providing them free to those in poverty, are estimated to be 95 times more cost effective than circumcision at reducing the rate of HIV in sub-Saharan Africa.

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. However, one randomized controlled trial indicated that adult male circumcision was not associated with increased HIV risk behaviour.

Exposure to infected body fluids

Health care workers can reduce exposure to HIV by employing precautions to reduce the risk of exposure to contaminated blood. These precautions include barriers such as gloves, masks, protective eye ware or shields, and gowns or aprons which prevent exposure of the skin or mucous membranes to blood borne pathogens. Frequent and thorough washing of the skin immediately after being contaminated with blood or other bodily fluids can reduce the chance of infection. Finally, sharp objects like needles, scalpels and glass, are carefully disposed of to prevent needle stick injuries with contaminated items. Since intravenous drug use is an important factor in HIV transmission in developed countries, harm reduction strategies such as needle-exchange programmes are used in attempts to reduce the infections caused by drug abuse.

Mother-to-child transmission (MTCT)

Current recommendations state that when replacement feeding is acceptable, feasible, affordable, sustainable and safe, HIV-infected mothers should avoid breast-feeding their infant. However, if this is not the case, exclusive breast-feeding is recommended during the first months of life and discontinued as soon as possible. It should be noted that women may breastfeed other children who are not their own.

Treatment

There is currently no publicly available vaccine for HIV or cure for HIV or AIDS. The only known methods of prevention are based on avoiding exposure to the virus or, failing that, an antiretroviral treatment directly after a highly significant exposure, called post-exposure prophylaxis (PEP). PEP has a very demanding four week schedule of dosage. It also has very unpleasant side effects including diarrhoea, malaise, nausea and fatigue.

Current treatment for HIV infection consists of highly active antiretroviral therapy, or HAART.  This has been highly beneficial to many HIV-infected individuals since its introduction in 1996 when the protease inhibitor-based HAART initially became available. 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. In developed countries where HAART is available, doctors assess the viral load, rapidity in CD4 decline, and patient readiness while deciding when to recommend initiating treatment.

Standard goals of HAART include improvement in the patient’s quality of life, reduction in complications, and reduction of HIV viremia below the limit of detection, but it does not cure the patient of HIV nor does it prevent the return, once treatment is stopped, of high blood levels of HIV, often HAART resistant. Moreover, it would take more than the lifetime of an individual to be cleared of HIV infection using HAART. Despite this, many HIV-infected individuals have experienced remarkable improvements in their general health and quality of life, which has led to the plummeting of HIV-associated morbidity and mortality. In the absence of HAART, progression from HIV infection to AIDS occurs at a median of between nine to ten years and the median survival time after developing AIDS is only 9.2 months. HAART is thought to increase survival time by between 4 and 12 years.

For some patients, which can be more than fifty percent of patients, 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.  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. Side effects can also deter people from persisting with HAART, these include, dyslipidaemia, diarrhoea, insulin resistance, an increase in cardiovascular risks and birth defects.  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.

Experimental and proposed treatments

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.

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. 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.

Researchers have discovered an enzyme 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.

In Berlin, Germany, a 42-year-old leukaemia patient 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. 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.

Alternative medicine

In the US, approximately 60% of HIV patients use various forms of alternative medicine to treat symptoms or alter the course of the disease. Despite the widespread use of CAM by people living with HIV/AIDS, the effectiveness of these therapies has not been established. Well-controlled studies with alternative therapies are rare, but those studies that are well-controlled have demonstrated promising results indicating the need for further research with larger sample sizes. Acupuncture has been used to alleviate some symptoms with no success and cannot cure the HIV infection.  Several randomized clinical trials testing the effect of herbal medicines have shown that there is no evidence that these herbs have any effect on the progression of the disease, but may instead produce serious side-effects.

Morbidity and mortality among HIV-infected adults with adequate dietary nutritional intake is unaffected by multivitamin supplementation. A large Tanzanian trial in immunologically and nutritionally compromised pregnant and lactating women showed a number of benefits to daily multivitamin supplementation for both mothers and children. Dietary intake of micronutrients at RDA levels by HIV-infected adults is recommended by the World Health Organization. There is some evidence that vitamin A supplementation in children reduces mortality and improves growth. Daily doses of selenium can suppress HIV viral burden with an associated improvement of the CD4 count. Selenium can be used as an adjunct therapy to standard antiviral treatments, but cannot itself reduce mortality and morbidity.

Prognosis

Without treatment, the net median survival time after infection with HIV is estimated to be 9 to 11 years, depending on the HIV subtype, and the median survival rate after diagnosis of AIDS in resource-limited settings where treatment is not available ranges between 6 and 19 months, depending on the study. In areas where it is widely available, the development of HAART as effective therapy for HIV infection and AIDS reduced the death rate from this disease by 80%, and raised the life expectancy for a newly diagnosed HIV-infected person to about 20 years.

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. Most patients die from opportunistic infections or malignancies associated with the progressive failure of the immune system. 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  health care and co-infections, as well as which particular strain of the virus is involved.

Even with anti-retroviral treatment, over the long term HIV-infected patients 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.

The largest cause of AIDS morbidity today, globally, is tuberculosis co-infection. AIDS#Pulmonary_infections

Society and culture

Stigma

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

Religion and AIDS

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, which scientists feel is currently the only means of stopping the epidemic. Other issues involve religious participation in global health care services and collaboration with secular organizations such as UNAIDS and the World Health Organization.