AIDS (Acquired Immunodeficiency Syndrome)

HIV is the blood-borne virus that causes AIDS.

• AIDS stands for "acquired immunodeficiency syndrome."
• AIDS is an advanced stage of infection with the human immunodeficiency virus (HIV). HIV usually spreads from person to person through contact with infected sexual secretions or blood.
• People with AIDS have weakened immune systems that make them vulnerable to medical conditions and infections.
• For people infected with HIV, the risk of progression to AIDS increases with the number of years the person has the infection. The risk of progression to AIDS decreases by using highly effective antiretroviral therapy (ART) regimens.
• In people with AIDS, ART improves the immune system and substantially increases life expectancy. Many patients treated with ART have near-normal life expectancies.
• ART is a treatment that patients must continue for life. It is not a cure.
• It is possible for HIV to become resistant to some antiretroviral medications. The best way to prevent resistance is for the patient to take their ART as directed without fail. If the patient wants to stop a drug because of side effects, he or she should call the physician immediately.
• If a patient with HIV exposes another person to blood or potentially infectious fluids, the exposed person can take medications to reduce the risk of getting HIV.
• Research is underway to find a vaccine and cure for HIV.

Picture of the HIV/AIDS virus

AIDS is an acronym for acquired immunodeficiency syndrome." The human immunodeficiency virus (HIV) causes AIDS and represents the most advanced stage of HIV infection.

How HIV affects the immune system

HIV spreads through infected blood or fluids such as sexual secretions. Over time, the virus attacks the immune system, focusing on special cells called "CD4 cells" which are important in protecting the body from infections and cancers, and the number of these cells starts to fall. Eventually, the CD4 cells fall to a critical level, and/or the immune system weakens so much that it can no longer fight off certain types of infections and cancers. AIDS is an advanced stage of HIV infection.

HIV is a very small virus that contains ribonucleic acid (RNA) as its genetic material. When HIV infects animal cells, it uses a special enzyme, reverse transcriptase, to turn (transcribe) its RNA into DNA. ("Retroviruses" are viruses that use reverse transcriptase.) When HIV reproduces, it is prone to making small genetic mistakes or mutations, resulting in viruses that vary slightly from each other. This ability to create minor variations allows HIV to evade the body's immunologic defenses, essentially leading to lifelong infection, and has made it difficult to make an effective vaccine. The mutations also allow HIV to become resistant to antiretroviral medications.

Careful investigation has helped scientists determine where HIV came from. Studies have shown that HIV first arose in Africa. It spread from non-human primates to people early in the 20th century, possibly when humans came into contact with infected blood during a chimpanzee hunt. By testing stored blood samples, scientists have found direct evidence of a human being infected as long ago as 1959.

Once introduced into humans, HIV spread through sexual intercourse from person to person. As infected people moved around, the virus spread from Africa to other areas of the world. In 1981, U.S. physicians noticed that a large number of young men were dying of unusual infections and cancers. Initially, U.S. victims were gay men predominately, probably because the virus inadvertently entered this population first in this country and because the virus is transmitted easily during anal intercourse. However, it is important to note that heterosexual activity and contact with infected blood or secretions also efficiently transmits the virus. In Africa, which remains the center of the AIDS pandemic, most cases are heterosexually transmitted. In 1991, the news that Magic Johnson had acquired HIV heterosexually helped the country realize that the infection was not limited to men who had sex with men. Currently in the U.S., approximately 27% of new HIV infections are a result of heterosexual transmission.

Other major factors in the early days of AIDS was transmission from blood by injection drug use (IDU) with needle sharing and transfusions of blood and blood components. Before the ability to test for the virus in donated blood became available, transfusions infected numerous hemophiliacs and surgical patients.

In the years since people first identified the virus, HIV has spread to every corner of the globe and is one of the leading causes of infectious death worldwide. Statistics from the World Health Organization show that approximately 1.5 million people die each year from AIDS, and 240,000 of these are children. Worldwide, half of HIV-infected people are women. Two-thirds of current cases are in sub-Saharan Africa.

In the U.S., more than 1 million people have HIV infections, and approximately 40,000 are newly infected each year. Over the years, more than 600,000 people in the U.S. have died from AIDS, many of them during what should have been their most productive years of life.

AIDS is an advanced stage of HIV infection. People with AIDS often develop symptoms and signs of unusual infections or cancers largely due to the destruction of the CD4 cells in the immune system. When a person with HIV infection gets one of these infections or cancers, medical professionals refer to this as an "AIDS-defining condition." Significant, unexplained weight loss also is an AIDS-defining condition. Because common conditions like cancer or other viral conditions like infectious mononucleosis also can cause weight loss and fatigue, it is sometimes easy for a physician to overlook the possibility of HIV/AIDS. It is possible for people without AIDS to get some of these conditions, especially the more common infections like tuberculosis.

People with AIDS may develop symptoms of pneumonia due to Pneumocystis jiroveci, which rarely appears in people with normal immune systems. They also are more likely to get pneumonia due to common bacteria. Globally, tuberculosis is one of the most common infections associated with AIDS. In addition, people with AIDS may develop seizures, weakness, or mental changes due to toxoplasmosis, a parasite that infects the brain. Neurological signs also may be due to meningitis caused by the fungus Cryptococcus. A yeast infection of the esophagus called candidiasis may cause complaints of painful swallowing. Because these infections take advantage of the weakened immune system, health care providers refer to them as "opportunistic infections."

The weakening of the immune system associated with HIV infection can lead to unusual cancers like Kaposi's sarcoma. Kaposi's sarcoma develops as raised patches on the skin that are red, brown, or purple. Kaposi's sarcoma can also be present in the mouth, intestine, or respiratory tract. AIDS also may be associated with lymphoma (a type of cancer involving white blood cells).

In people with AIDS, HIV itself may cause symptoms. Some people experience relentless fatigue and weight loss, known as "wasting syndrome." Others may develop confusion or sleepiness due to infection of the brain with HIV, known as HIV encephalopathy. Both wasting syndrome and HIV encephalopathy are AIDS-defining illnesses.

Developing AIDS requires that the person acquire HIV infection. Risks for acquiring HIV infection include behaviors that result in contact with infected blood or sexual secretions, which pose the main risk of HIV transmission. These behaviors include sexual intercourse and injection drug use. The presence of sores in the genital area, like those caused by herpes, makes it easier for the virus to pass from person to person during intercourse. HIV also has been spread to health care workers through accidental sticks with needles contaminated with blood from HIV-infected people, or when broken skin contacted infected blood or secretions. Blood products used for transfusions or injections also may spread infection, although this has become extremely rare (less than one in 2 million transfusions in the U.S.) due to testing of blood donors and blood supplies for HIV. Finally, infants may acquire HIV from an infected mother either while they are in the womb, during birth, or by breastfeeding after birth.

The risk that HIV infection will progress to AIDS increases with the number of years since a person acquired the infection. If the HIV infection is untreated, 50% of people will develop AIDS within 10 years, but some people progress in the first year or two and others remain completely asymptomatic with normal immune systems for decades after infection. The risk of developing one of the complications that define AIDS is associated with declining CD4 cells, particularly to below 200 cells/ul.

Antiretroviral treatment substantially reduces the risk that HIV will progress to AIDS. In developed countries, the use of ART has turned HIV into a chronic disease that may never progress to AIDS. Conversely, if infected people are not able to take their medications or have a virus that has developed resistance to several medications, they are at increased risk for progression to AIDS.

To diagnose AIDS, the doctor will need (1) a confirmed, positive test for HIV ("HIV positive" test) and (2) evidence of an AIDS-defining condition or severely depleted CD4 cells.

Testing for HIV is a two-step process involving a screening test and a confirmatory test. Current guidelines recommend that the first step is a screening test that looks for a component of the virus, called p24 antigen, as well as antibodies against HIV. Specimens for testing come from blood obtained from a vein or a finger stick, an oral swab, or a urine sample. Results can come back in minutes (rapid tests) or can take several days, depending on the method that is used. If the screening HIV test is positive, a different test that looks for antibodies to either HIV-1, the most common form of this virus, or to HIV-2, a strain more common in select parts of the World, such as Western Africa, will confirm the results. If one of these tests is positive, it confirms infection with that particular type of HIV. If both tests are negative, then medical professionals perform a test looking for the virus to see if the initial screening assay detected the viral protein at a time when infection was new and antibodies had yet to develop.

Merely having HIV does not mean a person has AIDS. AIDS is an advanced stage of HIV infection and requires that the person have evidence of a damaged immune system. That evidence comes from at least one of the following:

• The presence of an AIDS-defining condition
• Measuring the CD4 cells in the body and showing that there are fewer than 200 cells per milliliter of blood
• A laboratory result showing that fewer than 14% of lymphocytes are CD4 cells

It is important to remember, however, that any diagnosis of AIDS requires a confirmed, positive test for HIV.

Antiretroviral medications are medications that fight HIV. Different antiretroviral medications target the virus in different ways. When used in combination with each other, they are very effective at suppressing the virus. It is important to note that there is no cure for HIV. ART only suppresses the reproduction of the virus and stops or delays the disease from progressing to AIDS. Most guidelines currently recommend that all HIV-infected people who are willing to take medications should have them initiated shortly after their HIV diagnosis. This delays or prevents disease progression, improve the overall health of an infected person, and makes it less likely that they will transmit the virus to their partners.

There are currently seven major classes of antiretroviral medications:

1. nucleoside reverse transcriptase inhibitors (NRTIs),
2. non-nucleoside reverse transcriptase inhibitors (NNRTIs),
3. protease inhibitors (PIs),
4. fusion inhibitors,
5. integrase inhibitors,
6. CCR5 antagonists, and
7. entry inhibitor.

People use these drugs in different combinations according to their needs and depending on whether the virus has become resistant to a specific drug or class of drugs. Treatment regimens usually consist of three to four medications at the same time. Combination treatment is essential because using only one class of medication by itself allows the virus to become resistant to the medication. There are now pills that contain multiple drugs in a single pill, making it possible to treat many people with a single pill per day.

Before starting ART, medical professionals usually perform blood tests to make sure the virus is not already resistant to the chosen medications. Health care providers may repeat these resistance tests if it appears the drug regimen is not working or stops working. Physicians instruct patients about the importance of taking all of their medications as directed and are told what side effects to watch for. Noncompliance with medications is the most common cause of treatment failure and can cause the virus to develop resistance to the medication. Because successful therapy often depends on taking several pills, it is important for the patient to understand that this is an "all or nothing" regimen. If the person cannot tolerate one of the pills, then he or she should call their physician, ideally prior to stopping any medication. Taking just one or two of the recommended medications is strongly discouraged because it allows the virus to mutate and become resistant. It is best to inform the HIV health care provider immediately about any problems so they can prescribe a better-tolerated combination.

There are two goals of treatment for pregnant women with HIV infection:

• to treat maternal infection and
• to reduce the risk of HIV transmission from mother to child.

Women can pass HIV to their babies during pregnancy, during delivery, or after delivery by breastfeeding. Without treatment of the mother and without breastfeeding, the risk of transmission to the baby is about 25%. With treatment of the mother before and during birth and with the treatment of the baby after birth, the risk decreases to less than 2%. Because of this benefit, doctors recommended that all pregnant women undergo routine HIV testing as part of their prenatal care. Once diagnosed, there are several options for treatment, although women cannot use some antiretroviral medications during pregnancy and others have not been studied during pregnancy. For example, recent data suggests that dolutegravir (Tivicay) should be avoided in women who may become pregnant so that exposure at conception does not occur. Fortunately, there are treatment regimens that have been shown to be well tolerated by most pregnant women, significantly improving the outcome for mother and child. The same principles of testing for drug resistance and combining antiretrovirals used for nonpregnant patients are used for pregnant patients. All pregnant women with HIV should receive ART treatment regardless of their CD4 cell count, although the choice of drugs may differ slightly from nonpregnant women. In developed countries, women also are instructed not to breastfeed their children.

Compliance with medications is important to provide the best outcome for mother and child. Even though a physician might highly recommend a medication regimen, the pregnant woman has a choice of whether or not to take the medicines. Studies have shown improved compliance when there is good communication between the woman and her doctor, with open discussions about the benefits and side effects of treatment. Compliance also improves with better social support, including friends and relatives.

Patients must continue medications throughout pregnancy, labor, and delivery. Some medicines, such as zidovudine (also known as AZT), can be given intravenously during labor, particularly for those women who do not have good viral suppression at the time of delivery. Patients need to continue other medications orally during labor to try to reduce the risk of transmission to the baby during delivery. If the quantity of virus in the mother's blood (viral load) is more than 1,000 copies/mL near the time of delivery, doctors will perform a scheduled cesarean delivery at 38 weeks gestation to reduce the risk of transmitting the virus during vaginal delivery. Women with HIV should continue taking ART after delivery for their own health.

If a pregnant woman with HIV infection does not take ART during pregnancy and goes into labor, medical professionals will still give her medications during labor. This reduces the risk of transmission of HIV. After delivery, health care providers will give the infant medication(s) for at least six weeks to reduce the risk of transmission of HIV. If the mother did not take ART during pregnancy or if the mother has a drug-resistant virus, medical professionals will treat infants with multiple medications. Health care providers test infants periodically in the first six months to ensure they have not acquired the virus.

The complications of HIV infection result mainly from a weakened immune system. The virus also infects the brain, causing degeneration, problems with thinking, or even dementia. This makes the person more vulnerable to certain types of conditions and infections (see Table 1). Treatment with ART can prevent, reverse, or mitigate the effects of HIV infection. Some patients on ART may be at risk for developing cholesterol or blood-sugar problems.

Although many effective medications are on the market, the virus can become resistant to any drug. This can be a serious complication if it means that a patient must use a less effective medicine. To reduce the risk of resistance, patients should take their medications as prescribed and call their physician immediately if they feel they need to stop one or more drugs.

Left untreated, HIV is usually a fatal illness with half of the people dying within nine months of diagnosis of an AIDS-defining condition. The use of ART has dramatically changed this grim picture. People who are on an effective ART regimen have life expectancies that are similar to or only moderately less than the uninfected population. Unfortunately, many people with HIV deal with socioeconomic issues, substance-abuse issues, or other problems that interfere with their ability or desire to take medications.

The search for a cure for HIV began as soon as researchers identified the virus. HIV is probably one of the most studied viruses in history. Scientists have a detailed knowledge of the virus' genes, and proteins, and understand how it functions. In fact, researchers chose the combinations of drugs that make up ART therapy because they attack different parts of the virus life cycle, causing it to malfunction. However, ART is not a cure and HIV patients must take the drugs for life. Even when viral levels are low, the virus is still present in the body.

One of the problems with finding a cure is that the virus can persist in cells throughout the body and potentially hide in areas that are difficult for drugs to reach, like the brain. New research is helping us understand how to treat viruses effectively in these secluded areas of the body. In addition, researchers are studying those infected cells that persist in the body to determine how they can be stimulated to produce viruses and/or be targeted for clearance from the body by novel therapies.

Sexual abstinence is completely effective in eliminating sexual transmission, but educational campaigns have not been successful in promoting abstinence in at-risk populations. Monogamous sexual intercourse between two uninfected partners also eliminates the sexual transmission of the virus. Using barrier methods, such as condoms, during sexual intercourse markedly reduces the risk of HIV transmission. These measures have had some success in blunting the rate of new cases, especially in high-risk areas such as sub-Saharan Africa or Haiti. As discussed above, medications may reduce the risk of HIV infection if used within hours of exposure. There also is data that if uninfected people can take antiretroviral medications, in particular, tenofovir disoproxil fumarate plus emtricitabine (TDF/FTC or Truvada) once daily, it markedly reduces the risk of sexual transmission. Perhaps the most effective way to reduce HIV transmission is for the HIV-infected partner to be on ART with undetectable levels of virus in their blood. As noted above, a pregnant woman with HIV can reduce the risk of passing the infection to her baby by taking medications during pregnancy and labor and avoiding breastfeeding. There is now growing data that those consistently suppressed on ART pose virtually no risk of transmitting sexually to their partners.

People can prevent needle-stick injuries by touching syringes with only one hand and by using more modern needles that have retractable sleeves. The use of gowns, gloves, masks, and eye protection can reduce the risk of exposure to infected secretions in high-risk settings. For intravenous-drug abusers, the use of clean needles and the elimination of needle sharing reduces the risk of transmission.