Diseases

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 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 be used to reduce the risk of HIV infection if used within hours of an 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, that 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. 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.

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. The first step is usually a screening test that looks for antibodies against the 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, the results are confirmed by a special test called a Western blot or indirect immunofluorescence assay test. A Western blot detects antibodies to specific components of the virus. The confirmatory test is necessary because the screening test is less accurate and occasionally will be positive in those who do not have HIV. Another way to diagnose HIV infection is to do a special test to detect viral particles in the blood. These tests detect RNA, DNA, or viral antigens. However, these tests are more commonly used for guiding treatment rather than for diagnosis.

To date, there is no effective vaccine for HIV. Several attempts have been made to make a vaccine but all have failed. This remains an active area of research.

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 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 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 the infection was acquired. 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/ml.Antiretroviral treatment substantially reduces the risk that HIV will progress to AIDS. In developed countries, 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. If AIDS is not treated, 50% of people will die within nine months of the diagnosis.

AIDS is an advanced stage of HIV infection. Because the CD4 cells in the immune system have been largely destroyed, people with AIDS often 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 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 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 associated with HIV infection can lead to unusual cancers like Kaposi's sarcoma. Kaposi's sarcoma develops as raised patches on the skin which are red, brown, or purple. Kaposi's sarcoma can spread to 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.

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 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.

AIDS is an acronym for acquired immunodeficiency syndrome." AIDS is caused by the human immunodeficiency virus (HIV) and represents the most advanced stage of HIV infection. How HIV affects the immune system HIV is spread through contact with 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 is weakened so much that it can no longer fight off certain types of infections and cancers. This advanced stage of HIV infection is called AIDS. 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. (Viruses that use reverse transcriptase are sometimes referred to as "retroviruses.") 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 AIDS came from. Studies have shown that HIV first arose in Africa. It spread from 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 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 gay 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. Twenty years ago, 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 were injection drug use (IDU) through needle sharing and transfusions of blood and blood components. Numerous hemophiliacs and surgical patients were infected through tranfusions before the ability to test for the virus in donated blood became available.In the years since the virus was first identified, 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 are currently infected with HIV, and approximately 50,000 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.

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 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.

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%. Because of this benefit, it is recommended that all pregnant women be routinely tested for HIV as part of their prenatal care. Once diagnosed, there are several options for treatment, although some antiretroviral 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 antiretrovirals that are used for nonpregnant patients are used for pregnant patients. All pregnant women with HIV should be treated with ART 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 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, particularly for those women who do not have good viral suppression at the time of delivery. Other medications are continued 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, scheduled cesarean delivery is done at 38 weeks gestation to reduce the risk of transmitting the virus during vaginal delivery. Women with HIV who otherwise meet criteria for starting antiretroviral therapy, per local guidelines or the patient's preference, 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, medications are still given during labor. This reduces the risk of transmission of HIV. After delivery, the infant will be given medication(s) for at least six weeks to reduce the risk of transmission of HIV. If the mother did not take HAART during pregnancy or if the mother has a drug-resistant virus, infants will be treated with multiple medications. Infants are tested periodically in the first six months to ensure they have not acquired the virus.

Medications that fight HIV are called antiretroviral medications. 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 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 being diagnosed with the infection. This delays or prevents disease progression, improves overall health of an infected person, and makes it less likely that they will transmit the virus to their partners.There are currently six major classes of antiretroviral medications: (1) nucleoside reverse transcriptase inhibitors (NRTIs), (2) non-nucleoside reverse transcriptase inhibitors (NNRTIs), (3) protease inhibitors (PIs), (4) fusion (entry) inhibitors, (5) integrase inhibitors, and (6) CCR5 antagonists. 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 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 available pills that contain multiple drugs in a single pill, making it possible for many people to be treated with a single pill per day.Before starting ART, blood tests usually are 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 HIV health care provider immediately about any problems so that a better-tolerated combination can be prescribed.

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. Feces, nasal secretions, saliva, sputum, sweat, tears, urine, and vomit are not considered infectious unless visibly bloody.The most commonly reported occupational exposures are

• an inadvertent needle stick (usually when drawing blood from someone with AIDS);
• a cut from a sharp object such as a scalpel that is contaminated with blood;
• exposure of mucous membranes to infectious fluid (mucous membranes that may be exposed to splashes of material include the mouth, nasal passages, and eyes);
• exposure of open sores or abraded/inflamed skin to infectious material.

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/on 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 antiretroviral medications. Current recommendations suggest two or more antiretroviral 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 turn out to 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 antiretroviral postexposure prophylaxis after these exposures. In part, this is because the HIV status of a sexual partner or drug user is not usually known by the exposed person. Nevertheless, the U.S. Centers for Disease Control and Prevention (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.

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 ART therapy were chosen because they attack different parts of the virus life cycle, causing it to malfunction. However, ART 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 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 effectively treat viruses in these secluded areas of the body. In addition, those infected cells that persist in the body are being studied to determine how they can be stimulated to produce virus and/or be targeted for clearance from the body by novel therapies.

There are a large number of studies currently under way that involve HIV-infected patients. These studies are registered in a central database that can be searched at http://clinicaltrials.gov.