AIDS

Infection by HIV

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 (a subset of 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 fewer than 200 CD4+ T cells per micro liter (µL) of blood, cellular immunity is lost, leading to the condition known as 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. 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 (people with the CCR5-Δ32 mutation have shown resistance to infection with certain strains of HIV). HIV is genetically variable and exists as different strains, which cause different rates of clinical disease progression. 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 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

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 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 bacterialinfections 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

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 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, donor blood and blood products used in medicine and medical research are screened for HIV. 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 3–6 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. For the diagnosis of HIV infection these assays are not specifically approved, but are nonetheless routinely used in developed countries.

Symptoms and Complications

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. HIV affects 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. After the diagnosis of AIDS is made, the current average survival time with antiretroviral therapy (as of 2005) is estimated to be more than 5 years, 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. 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 factors relating to the viral strain. 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.

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. 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 run a significant risk of becoming infected.

Worldwide, approximately 30% of women report that their first sexual experience was forced or coerced, making sexual violence a key driver of the HIV/AIDS pandemic. Sexual assault greatly increases the risk of HIV transmission as protection is rarely employed and physical trauma to the vaginal cavity frequently occurs which facilitates the transmission of HIV.

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 micro ulceration; 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 STIs such as gonorrhea, Chlamydial infection and trichomoniasis which 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. Each 10-fold increment of blood plasma HIV RNA 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 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 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 effective use of condoms and screening of blood transfusion in North America, Western and Central Europe is credited with contributing to the low rates of AIDS in these regions. Promoting condom use, however, has often proved controversial and difficult. Many religious groups, most noticeably 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. Defenders of the Catholic Church's role in AIDS and general STD prevention state that, while they may be against the use of contraception, they are strong advocates of abstinence outside marriage. This attitude is also found among some health care providers and policy makers in sub-Saharan African nations, where HIV and AIDS prevalence is extremely high. 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, and abstinence-only programs have been unsuccessful both in changing sexual behavior and in reducing HIV transmission. 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.

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. Latex condoms degrade 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. 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 that must be scaled-up.

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.

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 just this. 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." However, criticism of the ABC approach is widespread because a faithful partner of an unfaithful partner is at risk of contracting HIV and that discrimination against women and girls is so great that they are without voice in almost every area of their lives. Other programs and initiatives promote condom use more heavily. Condom use is an integral part of the CNN Approach. This is:

• Condom use, for those who engage in risky behavior,
• Needles, use clean ones,
• Negotiating skills; negotiating safer sex with a partner and empowering women to make smart choices.

In December 2006, the last of three large, randomized trials confirmed that male circumcision lowers the risk of HIV infection among heterosexual African men by around 50%. It is expected that this intervention will be actively promoted in many of the countries worst affected by HIV, although doing so will involve confronting a number of practical, cultural and attitudinal issues. 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. Furthermore, South African medical experts are concerned that the repeated use of un-sterilized blades in the ritual circumcision of adolescent boys may be spreading HIV.

Exposure to Infected Body Fluids

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 not only HIV, but also hepatitis B and hepatitis C. Needle sharing is the cause of one third of all new HIV-infections and 50% of hepatitis C 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 that small risk. Health care workers (nurses, laboratory workers, doctors etc) are also concerned, although more rarely. This route can 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, supported by universal medical opinion on the matter, has urged the nations of the world to implement universal precautions to prevent HIV transmission in health care settings.

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 HIV infections worldwide are transmitted through the transfusion of infected blood and blood products".

Medical workers who follow universal precautions or body-substance isolation, such as wearing latex gloves when giving injections and washing the hands frequently, can help prevent infection by HIV.

All AIDS-prevention organizations advise drug-users not to share needles and other material required to prepare and take drugs (including syringes, cotton balls, the spoons, water for diluting the drug, straws, crack pipes, etc). It is important that people use new or properly sterilized needles for each injection. Information on cleaning needles using bleach is available from health care and addiction professionals and from needle exchanges. In some developed countries, clean needles are available free in some cities, at needle exchanges or safe injection sites. Additionally, many nations have decriminalized needle possession and made it possible to buy injection equipment from pharmacists without a prescription.

Mother-to-Child Transmission (MTCT)

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 the mother to the child during pregnancy, labor and delivery is 25%. However, when the mother has access to antiretroviral therapy and gives birth by caesarean section, the rate of transmission is just 1%. A number of factors influence the risk of infection, particularly the viral load of the mother at birth (the higher the load, the higher the risk). Breastfeeding increases the risk of transmission by 10–15%. This risk depends on clinical factors and may vary according to the pattern and duration of breast-feeding.

Studies have shown that antiretroviral drugs, caesarean delivery and formula feeding reduce the chance of transmission of HIV from mother to child. 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. In 2005, around 700,000 children under 15 contracted HIV, mainly through MTCT, with 630,000 of these infections occurring in Africa. Of the estimated 2.3 million [1.7–3.5 million] children currently living with HIV, 2 million (almost 90%) live in sub-Saharan Africa.

Prevention strategies are well known in developed countries, however, recent epidemiological and behavioral studies in Europe and North America have suggested that a substantial minority of young people continue to engage in high-risk practices and that despite HIV/AIDS knowledge, young people underestimate their own risk of becoming infected with HIV. However, transmission of HIV between intravenous drug users has clearly decreased, and HIV transmission by blood transfusion has become quite rare in developed countries.

Treatment

There is currently no vaccine 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 diarrhea, 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 anti-retroviral 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.

HAART allows the stabilization of the patient’s symptoms and viremia, but it neither cures the patient of HIV, nor alleviates the symptoms, and high levels of HIV-1, often HAART resistant, return once treatment is stopped. 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. Still, for some patients - and in many clinical cohorts this may be more than fifty percent of patients - HAART achieves far less than optimal results. This is due to a variety of reasons such as medication intolerance/side effects, prior ineffective antiretroviral therapy and infection with a drug-resistant strain of HIV. However, non-adherence and non-persistence with antiretroviral therapy is the major reason most individuals fail to get any benefit from and develop resistance to HAART. The reasons for non-adherence and non-persistence with HAART are varied and overlapping. Major psychosocial issues, such as poor access to medical care, inadequate social supports, psychiatric disease and drug abuse contribute to non-adherence. The complexity of these HAART regimens, whether due to pill number, dosing frequency, meal restrictions or other issues along with side effects that create intentional non-adherence also has a weighty impact. The side effects include lipodystrophy, dyslipidaemia, 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. 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. Only a vaccine is postulated to be able to halt the pandemic. This is because a vaccine would possibly cost less, thus being affordable for developing countries, and would not require daily treatments. However, after over 20 years of research, HIV-1 remains a difficult target for a vaccine.

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. Daily multivitamin supplements have been found to reduce HIV disease progression among men and women. This could become an important low-cost intervention provided during early HIV disease to prolong the time before antiretroviral therapy is required.

Various forms of alternative medicine have been used to treat symptoms or alter the course of the disease. In the first decade of the epidemic when no useful conventional treatment was available, a large number of people with AIDS experimented with alternative therapies. The definition of "alternative therapies" in AIDS has changed since that time. Then, the phrase often referred to community-driven treatments, untested by government or pharmaceutical company research, that some hoped would directly suppress the virus or stimulate immunity against it. These kinds of approaches have become less common over time as the benefits of AIDS drugs have become more apparent. Examples of alternative medicine that people hoped would improve their symptoms or their quality of life include massage, herbal and flower remedies and acupuncture; when used with conventional treatment, many now refer to these as "complementary" approaches. None of these treatments have been proven in controlled trials to have any effect in treating HIV or AIDS.

Origin of HIV

AIDS was first reported June 5, 1981, when the U.S. Centers for Disease Control and Prevention recorded a cluster of Pneumocystis carinii pneumonia (now classified as Pneumocystis jiroveci pneumonia) in five homosexual men in Los Angeles. Originally dubbed GRID, or Gay-Related Immune Deficiency, health authorities soon realized that nearly half of the people identified with the syndrome were not homosexual men. In 1982, the CDC introduced the term AIDS to describe the newly recognized syndrome.

Three of the earliest known instances of HIV infection are as follows:

• A plasma sample taken in 1959 from an adult male living in what is now the Democratic Republic of the Congo.
• HIV found in tissue samples from a 15 year old African-American teenager who died in St. Louis in 1969.
• HIV found in tissue samples from a Norwegian sailor who died around 1976.

Two species of HIV infect humans: HIV-1 and HIV-2. HIV-1 is more virulent and more easily transmitted. HIV-1 is the source of the majority of HIV infections throughout the world, while HIV-2 is not as easily transmitted and is largely confined to West Africa. Both HIV-1 and HIV-2 are of primate origin. The origin of HIV-1 is the Central Common Chimpanzee (Pan troglodytes troglodytes) found in southern Cameroon. It is established that HIV-2 originated from the Sooty Mangabey (Cercocebus atys), an Old World monkey of Guinea Bissau, Gabon, and Cameroon.

Most experts believe that HIV probably transferred to humans as a result of direct contact with primates, for instance during hunting or butchery. 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 polio vaccine. According to scientific consensus, this scenario is not supported by the available evidence.

Alternative Hypotheses

A small minority of scientists and activists question the connection between HIV and AIDS, the existence of HIV itself, or the validity of current testing and treatment methods. These claims are considered baseless by the vast majority of the scientific community. The medical community argues that so-called "AIDS dissidents" selectively ignore evidence in favor of HIV's role in AIDS and irresponsibly pose a threat to public health by discouraging HIV testing and proven treatments.

AIDS dissidents assert that the current mainstream approach to AIDS, based on HIV causation, has resulted in inaccurate diagnoses, psychological terror, toxic treatments, and a squandering of public funds. Dissident views have been examined and widely rejected, and are considered pseudoscience by the mainstream scientific community.

HIV and AIDS Misconceptions

A number of misconceptions have arisen surrounding HIV/AIDS. Three of the most common are that AIDS can spread through casual contact, sexual intercourse with a virgin will cure AIDS, and HIV can infect only homosexual men and drug users.

When scientists first recognized the syndrome in 1981 initially they termed it Gay Related Immune Deficiency Syndrome, a possible source for the misconception holding that AIDS infects only homosexual men; scientists soon renamed the disease in recognition of transmission other than by male-male intercourse.

HIV appears to have entered the United States around the late 1960s and seems to have then been unknowingly spread by people throughout the U.S. and Europe. In a survey on AIDS conducted in 1983 in Belgium, Denmark, Finland, France, Germany, Italy, the Netherlands, Norway, Sweden, Switzerland, and the United Kingdom a majority of those infected with HIV were male homosexuals (58% of all cases).