General Information About AIDS
What does AIDS stand for? What causes AIDS?
AIDS stands for "acquired immunodeficiency syndrome." AIDS is a disease that weakens the immune system to the point where an affected person is vulnerable to a wide range of infections and cancers that result in death if not treated. AIDS is caused by the human immunodeficiency virus (HIV). The virus is spread through contact with infected blood or secretions. At first (stage 1 HIV infection), there is little evidence of harm. 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 (stage 2). Eventually, the CD4 cells fall to a critical level and/or the immune system is weakened so much that it can no longer fight off certain types of infections and cancers. This advanced stage of infection (stage 3) with HIV is called AIDS.
HIV is a very small virus that contains ribonucleic acid (RNA) as its genetic material. (Animal cells, plant cells, bacteria, parasites, and some viruses use deoxyribonucleic acid [DNA] as their primary genetic material rather than RNA.) When HIV infects animal cells, it uses a special enzyme, reverse transcriptase, to turn (transcribe) its RNA into DNA which, in turn, directs the formation of HIV RNA that can be used to form new HIV. This is different from the way human cells reproduce (directly transcribing their DNA into RNA), so HIV is classified as a "retrovirus." 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 medications.
What is the history of AIDS?
Careful investigation has helped scientists determine where AIDS came from. Studies have shown that the human immunodeficiency virus first arose in Africa. It spread from primates to people decades ago, possibly when humans came into contact with infected blood during a chimpanzee hunt. By testing stored blood samples, scientists have found evidence of human infection as long ago as 1959. Once introduced into humans, HIV was 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 predominately homosexual men, 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 the virus also is efficiently transmitted through heterosexual activity and contact with infected blood or secretions. In Africa, which remains the center of the AIDS pandemic, most cases are heterosexually transmitted.
In the years since the virus was first identified, AIDS has spread to every corner of the globe. Statistics from the World Health Organization show that approximately 2 million people die each year from AIDS, resulting in 15 million new orphan children. Worldwide, half of HIV-infected people are women and 6% are children under 15 years of age. Two-thirds of current cases are in sub-Saharan Africa.
In the U.S., more than 1 million people have been diagnosed with AIDS since the start of the epidemic. There are approximately 430,000 people currently living with AIDS in the U.S. Each year, another 37,000 people are newly diagnosed with AIDS. Over the years, more than half a million people in the U.S. have died from AIDS, many of them during what should have been their most productive years of life.
What are symptoms and signs of AIDS?
AIDS is an advanced stage of HIV infection. Because the CD4 cells in the immune system have been largely destroyed, people with AIDS develop symptoms and signs of unusual infections or cancers. When a person with HIV infection gets one of these infections or cancers, it is referred to as an "AIDS-defining condition." Examples of AIDS-defining conditions are listed in Table 1. Significant, unexplained weight loss is also an AIDS-defining condition. 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 is rarely seen 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. Complaints of painful swallowing may be caused by a yeast infection of the esophagus called candidiasis. Because these infections take advantage of the weakened immune system, they are called opportunistic infections.
The weakening of the immune system in AIDS can lead to unusual cancers like Kaposi's sarcoma. Kaposi's sarcoma develops as raised lesions on the skin which are red, brown, or purple. Kaposi's sarcoma can spread to the mouth, intestine, or respiratory tract. AIDS also may cause lymphoma (a type of cancer) of the brain or other types of lymphomas.
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.
What are risk factors for AIDS?
Because AIDS is caused by HIV, the risk factors for developing AIDS are the same as for HIV. Specifically, behaviors that result in contact with infected blood or secretions 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 has come into contact with 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. 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 the infection was acquired. If the HIV infection is untreated, 50% of people will develop AIDS within 10 years. This time is shortened if the person already has a weak immune system or if HIV was acquired through transfusion. Of people with HIV, the risk of progressing to AIDS is increased if there is evidence that the immune system is weakening as shown by falling levels of CD4 cells or if the virus is reproducing rapidly as shown by a high number of viral particles in the blood (high viral load).
Treatment substantially reduces the risk that HIV will progress to AIDS. In developed countries, use of highly active antiretroviral therapy (HAART) 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. If AIDS is not treated, 50% of people will die within nine months of the diagnosis.
How is AIDS diagnosed?
To diagnose AIDS, the doctor will need (1) a confirmed, positive test for HIV 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. The first step is a screening test that looks for antibodies against the HIV virus. Specimens for rapid testing come from blood obtained from a vein or a finger stick, oral swab, or urine sample. Results can come back as soon as 20 minutes. These rapid HIV tests are available in most emergency rooms as well as HIV counseling centers and public clinics. If the screening HIV test is positive, the results are confirmed by a special test called a Western Blot or indirect immunofluorescence assay test. The confirmatory test is necessary because the screening test is less accurate and occasionally can miss HIV infection or, more likely, diagnose HIV when it is not present.
Another way to diagnose HIV infection is to do a special test to determine how many viral particles are in the blood. This is not usually used for screening or confirmation but is helpful in guiding treatment.
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 might come from the presence of an AIDS-defining condition. Evidence might also come from directly measuring the CD4 cells in the body and showing that there are fewer than 200 cells per milliliter of blood or that fewer than 14% of lymphocytes are CD4 cells since a healthy person generally has more than 800 CD4 cells per milliliter of blood. It is important to remember that any diagnosis of AIDS requires a confirmed, positive test for HIV.
AIDS-defining conditions: Note that a diagnosis of AIDS also requires a confirmed, positive test for HIV.
Pneumonia caused by Pneumocystis jiroveci
Recurrent pneumonia in people over 12 years of age
Recurrent blood infections with Salmonella bacteria
Children with unexplained, serious, and recurrent bacterial infections
Yeast infection of the esophagus (swallowing tube) or lungs
Invasive uterine cervical cancer
Selected types of lymphoma, including Burkitt, immunoblastic, or lymphomas that start in the brain
Wasting syndrome caused by HIV
Certain parasites in the intestinal tract: cryptosporidiosis, isosporiasis
Certain fungal infections if found outside of the lungs: coccidioidomycosis, cryptococcosis, histoplasmosis
Infections with selected mycobacterium (relatives of the tuberculosis bacterium) outside the lung
Brain infection with the parasite toxoplasmosis
A viral brain infection called progressive multifocal leukoencephalopathy
What is the treatment for HIV/AIDS?
Medications that fight HIV are called anti-retroviral medications. Different anti-retroviral medications attack the virus in different ways. When used in combination with each other, they are very effective at suppressing the virus. These effective combinations are called highly active anti-retroviral therapy or HAART. It is important to note that there is no cure for AIDS or for HIV. HAART only suppresses reproduction of the virus.
All people with a diagnosis of AIDS should receive HAART therapy. Of course, it is even better to give the medications earlier in HIV infection to prevent progression to AIDS. Current Department of Health and Human Services guidelines recommend starting HAART when CD4 falls below 350 cells per milliliter. Most experts would also consider therapy if the viral load is more than 100,000 copies per milliliter or if the CD4 count is falling rapidly. Recent studies suggest that starting treatment earlier, at CD4 counts from 350 to 500 and possibly even when greater than 500 per milliliter, may be beneficial.
There are five major classes of anti-retroviral medications: (1) nucleoside reverse transcriptase inhibitors (NRTIs), (2) non-nucleoside reverse transcriptase inhibitors (NNRTIs), (3) protease inhibitors (PIs), (4) entry inhibitors, and (5) integrase inhibitors. These drugs are used in different combinations according to the needs of the patient and depending on whether the virus has become resistant to a specific drug or class of medications. Treatment regimens usually consist of three to four medications at the same time. The most commonly recommended regimen includes two medications from the NRTI class in combination with either a protease inhibitor or an NNRTI or, less commonly, an integrase inhibitor. Entry inhibitors and integrase inhibitors are relatively newer classes of anti-retroviral medications and are useful for those patients who have failed to respond to other agents or who have a resistant virus. Combination treatment with HAART is essential because using only one class of medication by itself allows the virus to become resistant to the medication.
Before starting HAART, blood tests are usually done to make sure the virus is not already resistant to the chosen medications. These resistance tests may be repeated if it appears the drug regimen is not working or stops working. Patients are taught 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 doctor quickly about any problems so that a better-tolerated combination can be prescribed. To reduce the number of pills needed each day, there are pills that contain multiple medications.
What is the treatment for HIV during pregnancy?
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 treatment of the baby after birth, the risk decreases to less than 2%. Some anti-retroviral medications cannot be used in pregnancy and others have not been studied in pregnancy. For example, the medication efavirenz (Sustiva) is usually avoided in early pregnancy or in women who are likely to become pregnant. 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 anti-retrovirals that are used for nonpregnant patients are used for pregnant patients. All pregnant women with HIV should be treated with HAART regardless of their CD4 cell count, although the choice of drugs may differ slightly from nonpregnant women.
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 that compliance is improved when there is good communication between the woman and her doctor, with open discussions about the benefits and side effects of treatment. Compliance also is improved with better social support, including friends and relatives.
Medications are continued throughout pregnancy, labor, and delivery. Some medicines, such as zidovudine (also known as AZT), can be given intravenously during labor. Other medications are continued orally during labor to try to reduce the risk of transmission to the baby during delivery. If the mother's HIV viral load is more than 1,000 copies near the time of delivery, scheduled cesarean delivery is done at 38 weeks gestation because of a higher risk for transmitting the virus during vaginal delivery. Women with HIV who otherwise meet criteria for starting anti-retroviral therapy should continue taking HAART after delivery for their own health. In the U.S., breastfeeding is not recommended if the mother has HIV.
If a pregnant woman with HIV infection does not take HAART during pregnancy and goes into labor, medications are still given during labor. This reduces the risk of transmission of HIV.
If the mother has AIDS, the infant is treated with zidovudine for six weeks after birth. Other medications may be added to the infant's regimen, especially if the virus is known to be resistant to some medications.
What is the treatment for non-HIV-infected people who are exposed to the genital secretions or blood of someone with HIV?
Blood and genital secretions from people with HIV are considered infectious and the utmost care should be taken in handling them. Fluids that are contaminated with blood also are potentially infectious. The most commonly reported exposures are an inadvertent needle stick (usually when drawing blood from someone with AIDS) or having mucous membranes or skin abrasions or open skin sores come into contact with infectious fluid. Mucous membranes include the mouth, rectum, or genital area. The average risk of HIV infection after a needle-stick injury is around 0.3% and after mucous-membrane exposure to blood is approximately 0.09%. For abraded skin exposure, the risk is estimated to be less than mucous membrane exposure. There also are some factors that may affect the risk for HIV transmission such as the amount of blood from the infected source. Deep injury from a needle, visible blood in the needle, or a needle that was being placed in an artery or vein are examples of higher-risk situations. The risk of transmission also depends on the number of virus particles in the blood, with higher viral loads leading to an increased risk of transmission.
If an exposure occurs, the exposed person can reduce the risk of getting HIV by taking anti-retroviral medications. Current recommendations suggest two or more anti-retroviral medications, depending on the risk of transmission and type of exposure. Medications should be started as soon as possible, preferably within hours of exposure and should be continued for four weeks, if tolerated. People who have been exposed should be tested for HIV at the time of the injury and again at six weeks, 12 weeks, and six months after exposure.
It is important to document that an exposure has occurred or was likely. A needle stick from a person with HIV or a person likely to have HIV constitutes a significant exposure. Medications should be started immediately. If it is unknown whether the person who is the source of the potentially infected material has HIV, the source person can be tested. Medications that were started immediately in the exposed person can be discontinued if the source person does not carry HIV. Potentially infectious material splashed in the eye or mouth, or coming into contact with non-intact skin, also constitutes an exposure and should prompt immediate evaluation to determine if medications should be started.
Other potential exposures include vaginal and anal sexual intercourse and sharing needles during intravenous drug use. There is less evidence for the role of anti-retroviral post-exposure prophylaxis after these exposures. Nevertheless, the U.S. Communicable Disease Center (CDC) recommends treatment for people exposed through sexual activity or injectable drug use to someone who is known to carry HIV. If the HIV status of the source is not known, the decision to treat is individualized. Concerned people should see their physician for advice. If a decision to treat is made, medications should be started within 72 hours of the exposure.
For every exposure, especially with blood, it is important to test for other blood-borne diseases like hepatitis B or C, which are more common among HIV-infected patients. Reporting to a supervisor, in the case of health-care workers, or seeking immediate medical consultation is advisable. For sexual exposures, testing for syphilis, gonorrhea, chlamydia, and other sexually transmitted diseases (STDs) usually should be done because individuals with HIV are more likely to have other STDs. Patients also should be counseled about how to prevent exposure in the future.
What are the complications of HIV?
The complications of HIV infection result mainly from a weakened immune system. This makes the person more vulnerable to certain types of conditions and infections (see table). Treatment with HAART can reverse or mitigate the effects of HIV infection. Some patients on HAART 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 less effective medicine must be used. 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.
What is the prognosis for HIV infection?
Left untreated, HIV is almost always a fatal illness with half of people dying within nine months of diagnosis of an AIDS-defining condition. The use of HAART has dramatically changed this grim picture. People who are on an effective HAART regimen have life expectancies that are similar to or only moderately less than the uninfected population. Unfortunately, many people with AIDS have social issues, substance-abuse issues, or other problems that interfere with their ability or desire to take medications.
Can AIDS be prevented?
AIDS can be prevented. The best means of prevention is not to get HIV in the first place. 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 sexual transmission of the virus. Using barriers, such as condoms, during sexual intercourse reduces but does not eliminate the risk of viral transmission.
Needle-stick injuries can be prevented by touching syringes with only one hand and by using more modern needles that have retractable sleeves. 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, use of clean needles and elimination of needle sharing reduces the risk of transmission.
If a person already has HIV, he or she can reduce the risk of progressing to AIDS by taking an effective HAART regimen. 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.
Is there a vaccine for HIV?
To date, there is no effective vaccine for HIV. Several attempts have been made to make a vaccine but all have failed. One recent trial is more promising, but the vaccine being tested was not very effective.
What research is being done to find a cure for HIV?
The search for a cure for HIV began as soon as the virus was identified. HIV is probably one of the most studied viruses in history. Scientists have a detailed knowledge of the virus' genes, proteins, and understand how it functions. In fact, the combinations of drugs that make up HAART therapy were chosen because they attack different parts of the virus life cycle, causing it to malfunction. However, HAART therapy is not a cure and the drugs must be taken 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 hide in areas that are difficult for drugs to reach, like the brain. New research is helping us understand how to effectively treat viruses in these secluded areas of the body. In addition, the virus can become dormant or "latent," which means that it is not very metabolically active and cannot be attacked by medicines. Latent viruses can reactivate if drugs are stopped. Research is being done now to determine how latency occurs and how the virus reactivates.
AIDS At A Glance
* AIDS stands for "acquired immunodeficiency syndrome."
* AIDS is an advanced stage of infection with the human immunodeficiency virus (HIV). HIV is spread from person to person through contact with infected secretions or infected blood.
* People with AIDS have weakened immune systems that make them vulnerable to selected conditions and infections.
* For people infected with HIV, the risk of progression to AIDS increases with the number of years the person has been infected. The risk of progression to AIDS is decreased by using highly effective treatment regimens called HAART.
* In people with AIDS, HAART therapy improves the immune system and substantially increases life expectancy. Many patients who are treated with HAART have near-normal life expectancies.
* HAART is a treatment that must be continued for life. It is not a cure.
* It is possible for HIV to become resistant to some of the HAART medications. The best way to prevent resistance is for the patient to take their HAART medications as directed. If the patient wants to stop a drug because of side effects, he or she should call the physician immediately.
* If a person is exposed to blood or potentially infectious fluids from a source patient with HIV, the exposed person can take medications to reduce the risk of getting HIV.
* Research is under way to try to find a vaccine and a cure for HIV.
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