HIV/AIDS

AIDS is the abbreviation for acquired immunodeficiency syndrome, a condition first reported in the United States in 1981 that has since become a major worldwide epidemic. As of 2001, about 40 million people worldwide were infected, and the number today is far greater.

AIDS is an infectious, contagious disease caused by HIV (human immunodeficiency virus), a virus belonging to a group called the retroviruses. HIV progressively destroys a person's ability to fight infections and certain cancers by killing or damaging cells of the immune system. The term AIDS applies to the most advanced stages of HIV infection. Not everyone who has HIV has AIDS, but if their HIV is untreated, most will develop AIDS.

Other Names

 * Acquired immune deficiency syndrome

Types
There are two forms of the HIV virus: HIV-1 and HIV-2. The two types are spread the same way, and both lead to AIDS. They have some differences, though.

Both HIV-1 and HIV-2 have the same modes of transmission, and both cause immunosuppression (weakening of the immune system) in the same way. But in people infected with HIV-2, immunosuppression seems to progress more slowly, and the degree of immunosuppression is less than that caused by HIV-1.

The distinction between HIV-1 and HIV-2 is important since some early blood tests for HIV did not detect infection caused by HIV-2. This allowed HIV-2 to penetrate into the U.S. blood supply before 1992. Since 1992, however, all U.S. blood donors are tested for both HIV-1 and HIV-2.

HIV-1
HIV-1 is the original virus identified in the U.S. in 1983. It currently accounts for the most worldwide disease, with over 99.6% of HIV cases caused by HIV-1.

HIV-2
HIV-2 was isolated in 1986 from people with AIDS in west Africa. It is thought to have present in the population for a long time previously. It is still found mostly in West Africa. Immune system damage in HIV-2 patients tends to come more slowly than it does in HIV-1. It accounts for about one-tenth of one percent of HIV infections worldwide.

Signs and Symptoms
HIV mainly causes illness by damaging the immune system (immunosuppression). HIV can also directly cause illness by infecting the brain and other areas of the body. People infected with HIV can progress through several stages of illness related to the health of the immune system.

Primary infection (acute retroviral syndrome)

Between 40% and 90% of people infected with HIV can have an acute (rapid onset) retroviral syndrome. These symptoms may be mistaken for the flu or some other viral illness. The time between exposure to the virus and the beginning of symptoms has been reported to range from two to four weeks, with the illness generally lasting from one to two weeks. This period of infection represents the spread of HIV throughout the body. Symptoms include the following:
 * Fever
 * Swollen glands
 * Sweating, particularly at night
 * Aches and pains in the muscles and joints
 * Nausea, vomiting, and diarrhea
 * Headaches
 * Photophobia (sensitivity of the eyes to light)
 * Rash
 * Mouth sores
 * Fatigue

Less common symptoms include:
 * Guillain-Barre Syndrome
 * Stiff neck and headache due to meningitis
 * Paralysis or weakness in the muscles
 * Numbness or tingling in the arms or legs (neuropathy)

Period of latency

After the acute viral syndrome resolves, the person infected with HIV feels better and usually has no symptoms for months to years. Although this is called a period of latency (inactivity), HIV is, in fact actively damaging the immune system. As the disease progresses in untreated people, swelling of the lymph glands can occur in the head and neck, armpits, groin, and other areas. These glands are usually painless and feel rubbery, and they do not go away. During this stage, people with HIV often complain of being easily fatigued and report the need to reduce their normal daily activities and take frequent rests.

Early clinical disease

After years of infection with HIV, the immune system can become irreparably damaged. People begin to experience increased symptoms of a weakened immune system. These symptoms can include the following:
 * Thrush: An infection of the tongue and mouth caused by a fungus called  Candida albicans
 * Painful ulcers in the mouth
 * Hairy leukoplakia: Raised, white patches in the mouth, usually on the sides of the tongue, that are painless
 * Polymyositis: Weakness and pain in the muscles
 * Increasing fatigue
 * Loss of appetite
 * Weight loss, with loss of both fat and muscle
 * Intermittent fevers
 * Skin rashes, or worsening of skin diseases such as seborrheic dermatitis
 * Increasing trouble with exercise
 * Bleeding or bruising due to a decrease in platelet count called idiopathic thrombocytopenic purpura
 * Recurrent diarrhea
 * Recurrent shingles
 * Pelvic inflammatory disease that is recurrent or associated with tubo-ovarian abscess

AIDS-indicator conditions

The Centers for Disease Control and Prevention (CDC) developed a case-definition for AIDS in 1986, and made a major revision in 1993. A case of AIDS is defined as someone who is infected with HIV and who has an illness that indicates their immune system is severely damaged (severe immunosuppression), or someone who has evidence on a specific lab test of severe immunosuppression.

The list of illnesses that define AIDS is quite long. Some of the more common conditions are as follows:
 * Pneumonia caused by Pneumocystis jirovecii (previously called Pneumocystis cariniior PCP)
 * Infection of the back of the eye (the retina) caused by cytomegalovirus
 * Abscess in the brain caused by Toxoplasma gondii
 * Kaposi Sarcoma, purple bumps that appear on the skin or internally, caused by a recently discovered virus, human herpesvirus 8 (HHV-8)

These illnesses occur in people infected with HIV because of the severe immune damage that HIV can produce. These conditions are generally only seen in people who have a damaged immune system. Pneumocystis pneumonia or Cytomegalovirus retinitis are called opportunistic infections because they have an opportunity to make a person with a weak immune system sick (they do not ordinarily affect healthy people).

The symptoms of AIDS, therefore, depend on which indicator diseases a person infected with HIV has developed. People with Pneumocystis pneumonia, for example, can have shortness of breath, fever, and cough, while a person with a brain abscess from T. gondii can have severe headaches, lethargy, loss of consciousness, or paralysis.

Besides attacking the immune system, HIV can also cause disease directly in certain organs such as the brain. HIV infection of the brain is called HIV encephalopathy, and symptoms can include forgetfulness, lethargy, confusion, change in personality, and coma.

Causes
AIDS is caused by the retrovirus human immunodeficiency virus (HIV). This virus was first identified in 1983 by independent research groups from France and the United States.

HIV is different from most other viruses that infect humans because it attacks immune cells that are part of the body's defense against infections and against the development of certain cancers. HIV infects primarily CD4+ T-lymphocytes (also called T-helper cells), which are key cells in the immune system. Once HIV enters a T-helper cell, the cell becomes a factory to make more HIV. HIV particles bud off from the surface of the T-helper cell and infect other cells. The T-helper cell eventually dies. If enough T-helper cells die, the immune system becomes impaired and is unable to respond adequately to infections caused by other organisms. This immunosuppressed state is a hallmark of AIDS.

Diagnosis of HIV infection
There are several tests that can be used to determine whether someone has been infected with HIV. The most common test used is the HIV antibody test. This is a blood test that detects antibodies (proteins) that are made by the body in an attempt to fight off HIV. Antibodies to HIV typically appear two to eight weeks after the initial infection. Thus, this test is usually not useful in the diagnosis of acute or early HIV infection. The test most commonly used for detecting antibodies is the enzyme-linked immunoassay or ELISA. If the ELISA is positive, a confirmatory test is done called a Western blot. ELISA tests can also be used to detect anti-HIV antibodies in other body fluids such as urine or fluid from the mouth (not saliva).

One home testing kit has been approved by the Food and Drug Administration (FDA). It is actually a home collection kit. The testing procedure involves pricking the finger to obtain a drop of blood which is placed on a specially treated card. This card is then sent through the mail to a licensed testing laboratory. Customers can phone in for test results using an identification number and can speak to a counselor at any time during the process.

There have been reports of people being infected with HIV, yet having no antibodies detectable on a blood test. Such antibody-negative cases appears to be rare.

Another test that is used to detect HIV infection is the HIV antigen test. Antigens are proteins that are made by the virus, or parts of the structure of the virus. These antigens can be detected by a number of licensed tests, which assess the disease's activity. A high level of HIV antigen in the blood, or viremia, indicates that the virus is very active. This is typically seen soon after infection occurs, and later in the illness when the immune system has become weakened. This test is most useful as a measure of the patient's response to antiretroviral therapy in clinical practice and research programs. It has also been found to be a predictor of disease outcome.

More advanced blood tests can be used to detect HIV resistance to the currently available antiretroviral drugs. These tests are called genotypic or phenotypic assays, and their use can help doctors decide which antiretroviral drug to use in a particular patient.

Diagnosis of AIDS
The diagnosis of AIDS is made by following the criteria set forth by the Centers for Disease Control and Prevention (CDC). Although these are surveillance guidelines, the criteria are used in clinical practice to make a diagnosis of AIDS.

To meet the case definition of AIDS, a person must have the following: and either
 * Infection with HIV-1 or HIV-2 as determined by a blood test (see below),
 * A disease indicative of a severely weakened immune system (see Signs and Symptoms), or
 * A CD4+ T-lymphocyte count less than 200 cells/µL.

The T-cell count, a measure of the number of circulating CD4+ T-lymphocytes, can be used to measure the severity of immune damage caused by HIV. CD4+ T-lymphocytes are important cells in the immune system. Among other things, they are responsible for helping the immune system recognize and attack certain types of microbes and cancer cells. When these cells are destroyed by HIV, the end result is a severe weakening of the immune system and increased susceptibility to infections and certain types of cancer.

Treatment
Therapies for AIDS involve two distinct areas: treatment of HIV directly with antiretroviral drugs, and treatment of opportunistic infections and related conditions. Opportunistic infections are infections that occur in people with a weakened immune system.

Antiretroviral therapy
Treatment for AIDS and HIV infection has improved steadily since the advent of combination antiretroviral therapy in 1996. Antiretroviral agents are medications that have been found to inhibit HIV. Recently, new classes of drugs have been developed that offer new ways of inhibiting HIV, added effectiveness, dosing convenience, and fewer side effects. At the present time, no antiretroviral drug cures HIV. Also, these drugs do not prevent a person infected with HIV from spreading the virus to others.

After the first antiretroviral agents were used, it became clear that HIV could quickly develop resistance to these agents. One approach to delaying the appearance of resistance has been to use combinations of antiretroviral drugs. No antiretroviral drug should be used alone&mdash;more than one drug should always be taken at once. Blood tests have also been developed which can detect the presence of mutations in HIV that can lead to resistance. These are the genotypic and phenotypic resistance assays.

Using information from CD4+ T-lymphocyte counts, the level of virus in the blood (antigen tests) and the information gained from resistance assays, a combination antiretroviral drug regimen can be developed that potentially provides long-term HIV control, few side effects, ease of administration and an improved quality of life. The number of antiretroviral agents that are FDA-approved is quite large.

Classes of drugs used to treat HIV infection include the following:

Nucleoside reverse transcriptase inhibitors (NRTIs)

NRTIs inhibit HIV by interfering with a viral enzyme called reverse transcriptase that HIV needs to make copies of itself. The first FDA-approved drug for the treatment of HIV infection, zidovudine (AZT, ZDV, Retrovir), was in this class. As with all antiretroviral medications, NRTIs should not be used alone. They must be used in combination with other anti-HIV drugs. Other NRTIs include stavudine (d4T, Zerit), lamivudine (3TC, Epivir), tenofovir (Viread), abacavir (ABC, Ziagen), and emtricitabine (Emtriva).

Non-nucleoside reverse transcriptase inhibitors (NNRTIs)

NNRTIs also inhibit the reverse transcriptase enzyme of HIV, but do so in a different way than the NRTIs. Non-nucleoside reverse transcriptase inhibitors are not effective against HIV-2 strains. Drugs in this class include efavirenz (EFV, Sustiva), nevirapine (NVP, Viramune), delavirdine (Rescriptor) and etravirine (ETV, ETR, Intelence).

Protease inhibitors (PIs)

The approval of protease inhibitors in 1995 led to a major change in the outcome of the disease for most people with HIV. The use of PIs in combination regimens has led to an increase in life span, improved quality of life, reduced viral burden and improvements in the immune system for people infected with HIV.

Protease inhibitors are structurally similar to the protease enzyme of HIV, and this enzyme is necessary for HIV to build copies of itself. The protease inhibitors block binding sites that the HIV protease uses, and thereby interfere with the production of infectious virions. PIs are effective against HIV-1 and HIV-2, and they inhibit HIV found in chronically infected cells. The NRTIs and NNRTIs are generally only effective against HIV that is being produced from newly infected cells, not HIV found in chronically infected cells.

Protease inhibitors include saquinavir (Invirase), ritonavir (Norvir), nelfinavir (Viracept), indinavir (Crixivan), amprenavir (Agenerase), tipranavir (Aptivus), darunavir (Prezista), atazanavir (Reyataz) and fosamprenavir (Lexiva).

Ritonavir is often used at a low dose in combination with other protease inhibitors. Ritonavir is a potent inhibitor of a liver enzyme system called cytochrome P450 which is responsible for metabolizing (breaking down) many drugs, including protease inhibitors. For example, adding a low dose of ritonavir to lopinavir, another PI, results in raised levels of lopinavir in the blood and increased effectiveness of lopinavir against HIV. This combination of lopinavir and ritonavir is available in a single pill called Kaletra.

Integrase inhibitors

Integrase inhibitors were approved by the FDA in 2007, for use with other anti-HIV agents in the treatment of HIV infection. Drugs in this class inhibit HIV by blocking an HIV enzyme called integrase, an enzyme that is used to insert HIV genetic code into the host cell’s genetic code. Currently, there is only one integrase inhibitor, raltegravir (Isentress).

Entry and fusion inhibitors

The FDA approved entry inhibitors for use with other anti-HIV agents in the treatment of HIV infection in 2007. Maraviroc (Selzentry) is currently the only approved drug in this class. It works by preventing HIV from attaching to a receptor on the surface of T-helper cells called CCR5. For most isolates of HIV, binding to the CCR5 receptor is a necessary step in the process of entering (infecting) the T-helper cell (these are called CCR5-tropic isolates of HIV). Some isolates, however, can use other receptors on the T-helper cell surface to enter the cell. Thus, maraviroc and other similar drugs would have little effect on these types of HIV. A blood test is available which can be used to detect CCR5-tropic forms of HIV.

Enfuvirtide (Fuzeon) is a fusion inhibitor, approved by the FDA in 2003 for use with other anti-HIV drugs in the treatment of HIV infection. Fusion inhibitors interfere with the entry of HIV into cells by inhibiting fusion of the HIV and T-helper cell membranes. Fusion of the membranes is required for HIV to enter cells. Enfuvirtide binds to an HIV protein called gp41 and prevents it from working. This prevents viral-cell fusion from occurring.

Treatment of opportunistic infections
Treatment of infections and other conditions, such as Kaposi sarcoma, that can occur in people with AIDS is complex. Specific therapies depend on which infection or condition is present. Often a person with AIDS needs to be on multiple medications for the treatment or prevention of these conditions.

Prevention
AIDS is first and foremost a (sexually transmitted disease (STD)). The best ways to prevent transmission of a sexually transmitted disease include the following:
 * Abstaining from sex, not having oral, anal, or vaginal sex.
 * Only having sex in a relationship with a single partner. Both partners should know the other's HIV status.
 * If both partners are infected with HIV, they should always use condoms to prevent transmission of other sexually transmitted illnesses and to prevent possible infection with a different strain of HIV (one that may be more resistant to antiretroviral drugs).
 * If only one partner is infected with HIV, they should use latex condoms with a lubricant every time they have sex. The uninfected partner should undergo testing for HIV infection on a regular basis.
 * Avoiding multiple sex partners.
 * Avoiding anonymous sex partners.
 * In the event of a possible exposure to HIV, getting tested.
 * Talking about HIV and other STDs with each partner before having sex. Asking a sexual partner if they have been tested for HIV.
 * Using a latex condom and lubricant during sex.
 * Not injecting illicit drugs (drugs not prescribed by a doctor).
 * Not sharing drug equipment, such as needles and syringes.
 * Not having sex while taking drugs or drinking alcohol because doing so may lead to risky behavior.

People who are infected with HIV should not donate blood, tissues, or body organs. They should also receive evaluation and treatment for other STDs.

Post-exposure prophylaxis
Research continues in the area of post-exposure prophylaxis (PEP). This term refers to the use of antiretroviral agents as soon as possible after an exposure to HIV (such as through an accidental needle stick, or after sexual assault) in an attempt to prevent infection with the virus. The CDC has published guidelines on the use of PEP after exposure to HIV.

HIV Vaccine Awareness Day and the "Be The Generation" HIV vaccine education initiative is discussed in the video donated by the NIH:

Risk factors
People who participate in the following activities are at increased risk of becoming infected with HIV.
 * Injecting drugs or steroids, during which the equipment used (such as needles, syringes, cotton, water) and blood is shared with others
 * Engaging in unprotected vaginal, anal, or oral sex (that is, sex without using a condom) with men :who have sex with men, with multiple partners, or with anonymous partners
 * Having sex in exchange for drugs or money
 * Having unprotected sex with someone who has any of the risk factors for HIV

In addition, people may have an increased risk of being infected with HIV if
 * They have been given a diagnosis of, or been treated for, hepatitis, tuberculosis (TB), or a sexually transmitted disease (STD), or
 * They have received a blood transfusion or clotting factor for hemophilia during the period 1978 through 1985.

How HIV/AIDS is Spread
HIV is a fragile virus. It cannot live for very long outside the body. As a result, the virus is not transmitted through day-to-day activities such as shaking hands, hugging, or a casual kiss. People cannot become infected from a toilet seat, drinking fountain, doorknob, dishes, drinking glasses, food, or pets. Nor can people get HIV from mosquitoes.

HIV is primarily found in the blood, semen, and/or vaginal fluid of an infected person. HIV is transmitted in three main ways:
 * Having anal, vaginal, or oral sex with someone already infected with HIV.
 * Sharing needles, syringes, and other equipment with someone infected with HIV.
 * Being exposed to HIV before or during birth or through breast feeding, in the case of infants.

In addition, HIV can be transmitted through transfusions if the donor blood is infected with the virus. However, since 1985, all donated blood in the United States has been tested for HIV-1, and since 1992, blood has additionally been checked for HIV-2. Better tests were introduced in 1995 and 1999, making detection even more sensitive. Therefore, the risk for HIV infection through the transfusion of blood or blood products is extremely low.

Related Videos
Andrew Kuper (President, LeapFrog Investment) talks about problems and solutions to the ongoing AIDS crisis in his native South Africa. The BigThink video is titled "The Future of AIDS in Africa":

In this additional video from BigThink, Dr. Anthony Fauci, Director of the National Institute of Allergy and Infectious Diseases at the National Institutes of Health, describes his projects with Tommy Thompson to fight malaria and AIDS in Africa:

This video discusses the importance of African-American men who have sex with other men needing to know their HIV status.

This video, produced by Discovery Health, provides an overview of the HIV/AIDS epidemic from 1981 through 2008. Footage courtesy of Associated Press (AP). It's part of Discovery Health's continuing medical education (CME) program, Managing Comorbidities of HIV/AIDS, featuring infectious disease expert, Dr. John Bartlett, and former CDC Director, Dr. Julie Geberding.

Clinical Trials
For a list of American government-sponsored clinical trials research HIV and/or AIDS, click here.

Research
Research on HIV and AIDS is a large industry. Pre-clinical and clinical trials are looking into the following areas:
 * New antiretroviral agents
 * New therapies for opportunistic infections
 * How HIV causes damage to the immune system and other cells in the body (pathogenesis)
 * Methods to reduce transmission of HIV, including male circumcision and microbicides (gels, creams or suppositories that can kill or neutralize bacteria and viruses)
 * Post-exposure prophylaxis: Using antiretroviral agents as soon as possible after an exposure to HIV to try to prevent infection
 * Whether heredity plays a role in preventing infection in some people
 * Vaccine research
 * Differences in progression of AIDS among different racial and ethnic groups
 * HIV-2
 * New methods for detecting HIV infection in people

Recent news
Recently, a large clinical trial studying a vaccine to prevent infection with HIV (the STEP trial) was stopped because of concerns that the vaccine was not working. In fact there is some preliminary evidence that the vaccine could increase the risk of becoming infected with HIV, but the final answer on this issue will require further analysis of the trial data. This outcome was not expected, but also not surprising, given the complexity of the interaction between HIV and the human immune system.

Since there is no cure for HIV infection, an anti-HIV vaccine is vital in the continuing battle against the virus. Biomedical researchers are further studying how HIV infects people and how the immune system attempts to fight the infection.

Controversy
The South African minister of health, Manto Tshabalala-Msimangagain, has advocated a special diet to treat AIDS. There is no evidence that this diet is effective. The president of South Africa, Thabo Mbeki, has claimed that HIV does not cause AIDS. The South African government did not make antiretroviral medication available to its HIV-positive citizens in the public health service until 2003.

History
Five cases of a new syndrome; Pneumocystis pneumonia, occurring in previously healthy men&mdash;were reported to the CDC in 1981. These five patients represented the first reported cases of AIDS in the United States. Within two years, the cause of AIDS was discovered by research teams in France and the United States. Initially, the virus was called HTLV-III/LAV (human T-cell lymphotropic virus, type III/lymphadenopathy-associated virus) but was renamed human immunodeficiency virus (HIV).

The earliest known case of HIV in a human was detected from a blood sample that was collected in 1959 from a man in Kinshasa, Democratic Republic of Congo. How he became infected is not known. Genetic analysis of this blood sample suggested that HIV may have stemmed from a single virus in the late 1940s or early 1950s.

Scientists identified a type of chimpanzee in West Africa as the source of HIV infection in humans. The virus most likely jumped to humans when humans hunted these chimpanzees for meat and came into contact with their infected blood. Over several years, the virus slowly spread across Africa and later into other parts of the world.

It took several years for scientists to develop a test to detect the virus, to understand how HIV was transmitted between humans, and to determine what people could do to protect themselves. During the early 1980s, as many as 150,000 people became infected with HIV each year. By the early 1990s, this rate had dropped to about 40,000 new infections each year, where it remains today.

AIDS cases began to fall dramatically in 1996, when new drugs became available -- particularly the protease inhibitors -- that helped stem the progression of HIV to full-blown AIDs. Today, more people than ever before are living with HIV/AIDS. CDC estimates that about 1 million people in the United States are living with HIV or AIDS. About one quarter of these people do not know that they are infected: not knowing puts them and others at risk.

Epidemiology
According to the 2008 report on the global AIDS epidemic released by UNAIDS, as of 2007, there were approximately 33 million people living with HIV or AIDS, and more than 2 million people died from AIDS globally.

The following statistics from WHO give an indication of the severity of the HIV/AIDS issue:


 * More than 25 million people have died of AIDS since 1981.
 * Africa has 11.6 million AIDS orphans.
 * At the end of 2007, women accounted for 50% of all adults living with HIV worldwide, and for 59% in sub-Saharan Africa.
 * Young people (under 25 years old) account for half of all new HIV infections worldwide.
 * In developing and transitional countries, 9.7 million people are in immediate need of life-saving AIDS drugs; of these, only 2.99 million (31%) are receiving the drugs.

At the end of 2003, an estimated 1,039,000 to 1,185,000 people were living with HIV in the United States. In 2006, there were 35,314 new cases of HIV/AIDS in adults, adolescents, and children diagnoses in the 33 states with long-term, confidential, name-based HIV reporting.

During the mid-to-late 1990s, advances in HIV treatments slowed the progression of HIV infection to AIDS and led to dramatic decreases in deaths among persons with AIDS living in the 50 states and the District of Columbia. In general, the trend in the estimated numbers of AIDS cases and deaths remained stable from 2002 through 2005. Estimates for 2006 suggest that the number of AIDS cases remained stable and that the number of deaths decreased. However, it is too early to determine whether this trend will hold. Better treatments have also led to an increase in the number of persons who survive longer and are living with AIDS.

'''Estimated numbers of AIDS diagnoses, deaths, and persons living with AIDS, 2002–2006, United States. Source: CDC.'''

Worldwide, HIV and AIDS continue to be a major health problem. Data from the World Health Organization are shown below.