WHAT ARE OPPORTUNISTIC INFECTIONS? In our bodies, we carry many germs bacteria, protozoa, fungi, and viruses.

. When our immune system is working, it controls these germs. But when the immune system is weakened by HIV disease or by some medications, these germs can get out of control and cause health problems. Infections that take advantage of weakness in the immune defenses are called opportunistic. The phrase opportunistic infection is often shortened to OI. The rates of OIs have fallen dramatically since the introduction of antiretroviral therapies; However, OIs are still a problem, especially for people who have not been tested for HIV. Many people still show up in hospitals with a serious OI, often pneumocystis pneumonia. This is how they learn they have HIV infection.

TESTING FOR OIs You can be infected with an OI, and test positive for it, even though you dont have the disease. For example, almost everyone with HIV tests positive for Cytomegalovirus (CMV). But it is very rare for CMV disease to develop unless the CD4 cell count drops below 50, a sign of serious damage to the immune system. To see if youre infected with an OI, your blood might be tested for antigens (pieces of the germ that causes the OI) or for antibodies (proteins made by the immune system to fight the germs). If the antigens are found, it means youre infected. If the antibodies are found, youve been exposed to the infection. You may have been immunized against the infection, or your immune system may have cleared the infection, or you may be infected. If you are infected with a germ that causes an OI, and if your CD4 cells are low enough to allow that OI to develop, your health care provider will look for signs of active disease. These are different for the different OIs.

OIs AND AIDS People who arent HIV-infected can develop OIs if their immune systems are damaged. For example, many drugs used to treat cancer suppress the immune system. Some people who get cancer treatments can develop OIs. HIV weakens the immune system so that opportunistic infections can develop. If you are HIVinfected and develop opportunistic infections, you might have AIDS.

In the US, the Center for Disease Control (CDC) is responsible for deciding who has AIDS. The CDC has developed a list of about 24 opportunistic infections. If you have HIV and one or more of these official OIs, then you have AIDS. The list is available at http://www.thebody.com/content/art14002.html

WHAT ARE THE MOST COMMON OIs? In the early years of the AIDS epidemic, OIs caused a lot of sickness and deaths. Once people started taking strong antiretroviral therapy (ART), however, a lot fewer people got OIs. Its not clear how many people with HIV will get a specific OI. In women, health problems in the vaginal area may be early signs of HIV. These can include pelvic inflammatory disease and bacterial vaginosis, among others. See fact sheet 610 for more information. The most common OIs are listed here, along with the disease they usually cause, and the CD4 cell count when the disease becomes active: Candidiasis (Thrush) is a fungal infection of the mouth, throat, or vagina. CD4 cell range: can occur even with fairly high CD4 cells. See Fact Sheet 501. Cytomegalovirus (CMV) is a viral infection that causes eye disease that can lead to blindness. CD4 cell range: under 50. See Fact Sheet 504. Herpes simplex viruses can cause oral herpes (cold sores) or genital herpes. These are fairly common infections, but if you have HIV, the outbreaks can be much more frequent and more severe. They can occur at any CD4 cell count. See Fact Sheet 508. Malaria is common in the developing world. It is more common and more severe in people with HIV infection. Mycobacterium avium complex (MAC or MAI) is a bacterial infection that can cause recurring fevers, general sick feelings, problems with digestion, and serious weight loss. CD4 cell range: under 50. See Fact Sheet 514. Pneumocystis pneumonia (PCP) is a fungal infection that can cause a fatal pneumonia. CD4 cell range: under 200. See Fact Sheet 515. Unfortunately, this is still a fairly common OI in people who have not been tested or treated for HIV. Toxoplasmosis (Toxo) is a protozoal infection of the brain. CD4 cell range: under 100. See Fact Sheet 517.

Tuberculosis (TB) is a bacterial infection that attacks the lungs, and can cause meningitis. CD4 cell range: Everyone with HIV who tests positive for exposure to TB should be treated. See Fact Sheet 518.

PREVENTING OIs Most of the germs that cause OIs are quite common, and you may already be carrying several of these infections. You can reduce the risk of new infections by keeping clean and avoiding known sources of the germs that cause OIs. Even if youre infected with some OIs, you can take medications that will prevent the development of active disease. This is called prophylaxis. The best way to prevent OIs is to take strong ART. See Fact Sheet 403 for more information on ART. The Fact Sheets for each OI have more information on avoiding infection or preventing the development of active disease.

TREATING OIs For each OI, there are specific drugs, or combinations of drugs, that seem to work best. Refer to the fact sheets for each OI to learn more about how they are treated. The full US guidelines for treating and preventing OIs can be found at http://www.aidsinfo.nih.gov/Guidelines/ and choosing "Prevention and Treatment of Opportunistic Infections Guidelines." Strong antiretroviral drugs can allow a damaged immune system to recover and do a better job of fighting OIs. Fact Sheet 481 on Immune Restoration has more information on this topic. WHAT IS THRUSH? Candidiasis is a common opportunistic infection in people with HIV. It is an infection caused by a common type of yeast (or fungus) called candida. This yeast is found in most peoples bodies. A healthy immune system keeps it under control. Candida usually infects the mouth, throat, or vagina. It can occur months or years before other, more serious opportunistic infections. See Fact Sheet 500 for more information on opportunistic infections. In the mouth, the infection is called thrush. When the infection spreads deeper into the throat it is called esophagitis. It looks like white patches similar to cottage cheese, or red spots. It can

cause a sore throat, pain when swallowing, nausea, and loss of appetite. Thrush can also cause cracking at the corners of the mouth. This is called angular chelitis. In the vagina, the infection is called yeast infection or vaginitis. This is a common vaginal infection. Symptoms include itching, burning, and a thick whitish discharge. Candida can also spread and cause infection in the brain, heart, joints, and eyes.

CAN IT BE PREVENTED? There is no way to prevent exposure to candida. Medications are not normally used to prevent candidiasis. There are several reasons for this:

It is not very dangerous There are effective drugs to treat it The yeast could develop resistance to the medications.

Strengthening your immune system by taking combination antiretroviral therapy (ART) is the best way to prevent an outbreak of candidiasis.

HOW IS IT TREATED? A healthy immune system keeps candida in balance. Bacteria normally found in the body also help control it. Some antibiotics kill these helpful bacteria and cause an outbreak of candidiasis. Treating candidiasis will not get rid of the yeast, but will keep it under control. Treatments can be local or systemic. Local treatments are applied where the infection is found. Systemic treatments affect the whole body. Many health care providers prefer to use local treatment first. It puts the medication directly where it is needed. It has fewer side effects than a systemic treatment. Also, there is less risk of candida becoming resistant to the medications. The medications used to fight candida are antifungal drugs. Almost all their names end in -azole. They include clotrimazole, nystatin, fluconazole, and itraconazole. Local treatments include: o Creams o suppositories to treat vaginitis o liquids o troches or lozenges that dissolve in the mouth.

Local treatments may cause some stinging or irritation.

Systemic treatment is needed if local treatments dont work, or if the infection has spread into the throat (esophagitis) or other parts of the body. Some systemic drugs are taken in pill form. The most common side effects are nausea, vomiting, and abdominal pain. Less than 20% of people have these side effects.

Candidiasis can come back repeatedly. Some health care providers prescribe anti-fungal drugs on a long-term basis. This can cause resistance. The yeast can mutate so that a drug no longer works. Some serious cases do not respond to other medications. Then, amphotericin B might be used. It is a very potent and toxic drug, given orally or intravenously. The major side effects are kidney problems and anemia. Other reactions include fever, chills, nausea, vomiting, and headache. These usually get better after the first few doses.

NATURAL THERAPIES Several non-drug therapies seem to help. They have not been carefully studied to prove that they work.

Reduce the amount of sugar you eat. Drink Pau dArco tea. It is made from the bark of a South American tree. Take garlic supplements or eat raw garlic. Garlic has anti-fungal and anti-bacterial properties. However, it can interfere with protease inhibitor drugs. Gargle with tea tree oil diluted in water. Take lactobacillus (acidophilus) capsules or eat yogurt with this bacteria. Make sure the label says it has live, active cultures. It may help to take it after taking antibiotics. Take supplements of gamma-linoleic acid (GLA) and Biotin. They both seem to slow the spread of candida. GLA is found in several cold-pressed oils. Biotin is a B vitamin.

THE BOTTOM LINE Candidiasis is a very common yeast (fungal) infection. The fungus normally lives in the body. It cannot be eliminated. The best way to avoid an outbreak of candidiasis is to strengthen your immune system by taking antiretroviral medications (ARVs).

Most candida infections are easily treated with local therapies. In people with weakened immune systems, these infections become more persistent. Systemic anti-fungal drugs can be taken, but candida might become resistant to them. The most potent anti-fungal drug, amphotericin B, has serious side effects. Several natural therapies seem to help control candida infections. WHAT IS CRYPTOSPORIDIOSIS? Cryptosporidiosis (crypto) is an infection caused by the parasite Cryptosporidium. A parasite gets its nutrients from another living organism (the host). Your body is the host when you have this infection. Crypto mainly affects the intestines and causes diarrhea. Crypto is easily spread by contaminated food or water, or direct contact with an infected person or animal. About 15% to 20% of people with AIDS are infected with crypto. Only some of these infections lead to serious disease. Crypto causes a lot of diarrhea, along with nausea, vomiting, and stomach cramps. In people with healthy immune systems, these symptoms do not last more than about a week. See Fact Sheet 554 for more information on diarrhea. However, the symptoms of crypto may continue for a long time if the immune system is damaged. This usually happens with CD4 cell counts below 200. If you have HIV infection, and crypto continues for 4 weeks or more, you have AIDS according to the guidelines of the Centers for Disease Control. Diarrhea can interfere with the absorption of nutrients. If it continues for a long time, you can develop serious weight loss (wasting, see Fact Sheet 519). Several diseases cause similar problems. To confirm a diagnosis, doctors usually check your stool (bowel movement) for parasites and their eggs. This is called an O and P or ova and parasites test.

CAN CRYPTO BE PREVENTED? There is no medication that prevents crypto. The best protection is cleanliness. Avoid contact with human or animal wastes. Wash your hands after using the bathroom, gardening, handling dirty laundry or animals, or changing diapers. Crypto can be transmitted through oral-anal sexual activity. Do not swallow water when swimming, since water may be contaminated with human or animal waste containing crypto. Raw oysters may carry crypto.

In some developing countries and in some US cities, the public water supply is contaminated with crypto. Check with your water department. If there is a problem, and your CD4 cell count (see fact sheet 124) is below 200, consider the following steps:

Boil drinking or cooking water for one minute; or Drink bottled water; or Drink filtered water: Use a home filter labeled 1-micron filter or Meets National Science Foundation (NSF) standard number 53 for cyst removal; or Drink distilled water. Bottled water may not be safe if it has not been boiled or filtered correctly.

For more information, see the CDC Prevention Guide at http://www.cdc.gov/hiv/resources/brochures/crypto.htm.

HOW IS CRYPTO TREATED? There is no cure for crypto; however, antiretroviral therapy (ART) will decrease or get rid of crypto symptoms. Nitazoxanide has been approved by the FDA for the treatment of crypto in children and adults. It is used along with ART. Some drugs approved for other uses can be used against cryptosporidiosis, including paromomycin (Humatin). We cant get rid of the crypto infection. However, there are ways to control the diarrhea it causes. These include Imodium, Kaopectate, Pepto-Bismol (bismuth subsalicylate), tincture of opium and similar preparations. . If you have diarrhea, it is important to drink plenty of fluids to avoid becoming dehydrated. You may also need to replace loat electrolytes (salts in body fluid.) Some drinks contain electrolytes.

THE BOTTOM LINE Cryptosporidium is a fairly common parasite. It is found in animals, humans, soil, and water. It can be transmitted easily. In people with normal immune systems, crypto causes diarrhea and other stomach problems for about a week. In people with less than 200 CD4 cells, the diarrhea may continue.

The best way to prevent infection by crypto is frequent hand washing. Also avoid contaminated water, or ice made with contaminated water. If your local water supply is contaminated with crypto, use only boiled or filtered water for cooking and drinking. The best treatment for crypto is antiretroviral therapy (ART). Adding nitazoxanide helps fight crypto. Chronic diarrhea due to crypto should be controlled in order to avoid dehydration, loss of electrolytes, and more serious problems like wasting.

WHAT IS CRYPTOCOCCAL MENINGITIS? Cryptococcus is a fungus. It is very common in the soil. It can get into your body when you breathe in dust or dried bird droppings. It does not seem to spread from person to person. Meningitis is the most common illness caused by Cryptococcus. Meningitis is an infection of the lining of the spinal cord and brain. It can cause coma and death. Cryptococcus can also infect the skin, lungs, or other parts of the body. The risk of cryptococcal infection is highest when your CD4 counts are below 100. Cryptococcal meningitis is a major HIV-related opportunistic infection, especially in the developing world. A recent study estimated that there are 1 million cases each year. The first signs of meningitis include fever, fatigue, a stiff neck, headache, nausea and vomiting, confusion, blurred vision or sensitivity to bright light. The symptoms may come on slowly. HIV disease or medications can cause some of these symptoms. Therefore, laboratory tests are used to confirm that you have meningitis. Also, people with HIV who start antiretroviral treatment and are infected with cryptococcus may develop these symptoms as part of the immune reconstitution syndrome (see fact sheet 483.) A study in 2011 showed that starting HIV therapy while treating cryptococcal meningitis increased the risk of IRIS. Better outcomes were obtained by treating the meningitis before starting anti-HIV treatment. The tests use blood or spinal fluid. Health care providers get spinal fluid by doing a spinal tap. A needle is inserted into the middle of your back just above your hips. The needle removes a sample of spinal fluid. The pressure of the spinal fluid can also be measured. If the pressure is too high, the health care provider may drain some of the fluid. The test is safe and usually not too painful. However, after a spinal tap some people get headaches that can last a few days. The blood or spinal fluid can be tested for cryptococcus in two ways. A CRAG test looks for an antigen (a protein) produced by cryptococcus. A culture is a way to see if the cryptococcus fungus can be grown from the sample of spinal fluid. CRAG tests are quick and can produce

same-day results. A culture can take a week or more to show a positive result. Spinal fluid can also be tested quickly using a stain.

HOW IS MENINGITIS TREATED? Meningitis is treated with antifungal drugs. Some physicians use fluconazole (see Fact Sheet 534). It is available in pill form or as an intravenous (IV) drug. Fluconazole is fairly effective, and is generally easy to tolerate. Itraconazole is sometimes used for people who cannot take fluconazole. Other health care providers prefer to use a combination of amphotericin B and flucytosine capsules. Amphotericin B is a very strong drug. It is given as an injection or a slow intravenous (IV) infusion. Both of these drugs can have serious side effects. Side effects can be reduced by taking Advil or Tylenol a half hour before taking the drug. In a newer form of amphotericin, the medication is encased in fat bubbles (liposomes). This form may have fewer side effects. Cryptococcal meningitis comes back after the first time in about half of the people who get it. Repeat cases are reduced if people keep taking antifungal drugs. However, a recent study found no recurrence of meningitis in people whose CD4 increased to more than 100 and who had an undetectable viral load (see fact sheet 125) for 3 months. For some people, draining spinal fluid daily to reduce pressure on the brain is also part of treatment. Starting antiretroviral therapy (ART) can cause problems if you have had cryptococcal infection for a short time. Talk to your health care provider.

HOW DO I CHOOSE A TREATMENT FOR MENINGITIS? If you have meningitis, you will be treated with antifungal drugs such as amphotericin B, fluconazole, and flucytosine. Amphotericin B is the strongest, but it can damage your kidneys. The other drugs have less serious side effects, but they are less effective at clearing out the cryptococcus. If meningitis is diagnosed early enough, it can be treated without using amphotericin B. The usual treatment, however, is two weeks of amphotericin B followed by oral fluconazole. The fluconazole is continued for life. Without it, the meningitis is likely to come back.

CAN MENINGITIS BE PREVENTED? Taking fluconazole when your CD4 count is below 50 can help prevent cryptococcal meningitis. But there are several reasons why most health care providers dont use it:

Most fungal infections are easy to treat. Fluconazole is a very expensive drug. Taking fluconazole for a long period of time can lead to yeast infections (such as thrush, vaginitis, or severe candida infection of the throat) that are resistant to fluconazole. These resistant infections can only be treated with Amphotericin B.

THE BOTTOM LINE Cryptococcal meningitis occurs most often in people with CD4 cell counts below 100. Although antifungal drugs can prevent cryptococcal meningitis, they are usually not used because of their high cost and the risk of developing drug-resistant yeast infections. If you get meningitis, early diagnosis might allow treatment with less toxic drugs. Contact your health care provider if you have headaches, a stiff neck, vision problems, confusion, nausea, or vomiting. If you develop meningitis, you will probably have to continue taking antifungal drugs to prevent the disease from coming back.

WHAT IS CMV?
Cytomegalovirus (CMV) is a virus that can cause an opportunistic infection (see fact sheet 500.) The virus is very common. Between 50% and 85% of the US population tests positive for CMV by the time they are 40 years old. A healthy immune system keeps this virus in check When the immune defenses are weak, CMV can attack several parts of the body. This can be caused by various diseases including HIV. Combination antiretroviral therapy (ART) has reduced the rate of CMV in people with HIV by 75%. However, about 5% of people with HIV still develop CMV disease. The most common illness caused by CMV is retinitis. This is the death of cells in the retinas, the back of the eye. It can quickly cause blindness unless treated. CMV can spread throughout the

body and infect several organs at once. The risk of CMV disease is highest when CD4 cell counts (see fact sheet 124) are below 50. It is rare in people with 100 or more CD4 cells. The first signs of CMV retinitis are vision problems such as moving black spots. These are called floaters. They may indicate an inflammation of the retina. Patients may also notice light flashes, decreased or distorted vision, or blind spots. Some doctors recommend eye exams to catch CMV retinitis. The exams are done by an ophthalmologist (an eye specialist). If your CD4 count is below 100 and you experience any vision problems, tell your health care provider immediately. Some patients who have recently started using ARTVs can get inflammation in their eyes, causing loss of vision. This is called immune restoration syndrome (See Fact Sheet 483). A recent study suggests that having active CMV infection makes it easier to pass HIV to others. CMV infection may cause ongoing inflammation (see fact sheet 484) even if you have no symptoms of CMV disease. CMV is reactivated in many people as part of normal aging. To reduce inflammation, CMV should be treated, even if it is not causing symptoms.

HOW IS CMV TREATED?

The first treatments for CMV required daily intravenous infusions. Most people had a permanent medication port inserted into their chest or arm. People had to keep taking anti-CMV drugs for life.CMV treatments have improved dramatically over the past several years. With strong HIV therapies, patients can stop taking CMV drugs if their CD4 cell count goes over 150 and stays there for at least three months. However, there are two special cases: Immune restoration syndrome can cause severe inflammation in the eyes of people with HIV even if they didnt have CMV before. The usual treatment is to add anti-CMV drugs to the patients ARVs. If the CD4 count drops below 50, there is an increased risk of developing CMV disease.

CAN CMV BE PREVENTED?

Ganciclovir was approved for prevention (prophylaxis) of CMV. However, many health care providers dont prescribe it. They dont want to add up to 12 capsules a day for their patients. Also, its not clear that it does any good. Two large studies came to different conclusions. Finally, strong ARVs keep most peoples CD4 counts high enough so that they wont get CMV.

HOW DO I CHOOSE A TREATMENT FOR CMV?

There are several issues to consider when choosing a treatment for active CMV disease:

Is your vision at risk? You need to take quick action to save your eyesight. How effective is it? Intravenous ganciclovir is the most effective overall CMV treatment. Implants are very good at stopping retinitis. However, they only work in the eye with the implant. How is it administered? Pills are the easiest to manage. Intravenous (IV) medication involves needle sticks or a medication line that might become infected. Ocular injections mean inserting a needle directly into the eye. Implants in the eye, which last six to eight months, take about an hour to insert in an office procedure. Is it a local therapy or systemic? Local therapies affect just the eyes. CMV retinitis can progress rapidly and lead to blindness. For this reason, it is treated aggressively when it first shows up. The newer injections or implants put medication directly into the eye and have the greatest impact on retinitis. CMV can also show up in other places in the body. To control CMV in the rest of the body, you need a systemic (whole-body) therapy. Intravenous medication or valganciclovir pills can be used. What are the side effects? Some CMV drugs can damage your bone marrow or kidneys. This may require additional medications. Other drugs require infusions that can take a long time. Discuss the side effects of any CMV treatment with your health care provider. What do the guidelines say? Recently, several sets of professional guidelines have recommended valganciclovir as the preferred treatment for patients who are not at immediate risk of losing their sight.

THE BOTTOM LINE

Strong ARVs are the best way to prevent CMV. If your CD4 cell count is below 100, talk with your health care provider about CMV prevention and a regular schedule of eye exams. If you have a low CD4 cell count and experience ANY unusual vision problems, see your health care provider immediately! Treatments directly in the eye make it possible to control CMV retinitis. With the newer drugs to treat CMV, you can avoid implanted medication lines and daily infusions. Most people can safely stop taking CMV medication if their CD4 cell counts go up and stay above 150 when they take ARVs.

WHAT ARE NERVOUS SYSTEM PROBLEMS? The nervous system has two parts. The brain and spinal cord are the central nervous system (CNS). The nerves and muscles are the peripheral (around the outside) nervous system. People with HIV disease can have several problems with the nervous system. A common problem is peripheral neuropathy. This can cause damage to nerves controlling sensation. Symptoms may include altered sensation, numbness, tingling, pain, or weakness, especially in the feet and legs. See Fact Sheet 555 for more information. Central nervous system (CNS) problems include depression and problems with sleeping, balance, walking, thinking, and memory. In the early years of AIDS these were all called HIV-Associated Dementia. However, a broader range of problems is showing up at present. This is now called HIV-associated Neurological Disturbances (HAND), which includes less severe symptoms referred to as Minor Cognitive Motor Disorder. Before combination antiretroviral therapy (ART) was available, about 20% of people with AIDS developed severe dementia. Strong antiretroviral medications (ARVs) have cut the rate of serious dementia. However, with longer survival, more people with AIDS are living with milder neurologic problems. These are estimated to affect 40% to 70% of people with HIV. This is true even if people are taking ART. The body has a mechanism to protect the brain from foreign substances. This is called the bloodbrain barrier. It keeps most HIV medications from getting into the brain. However, when the viral load in blood goes down, it also goes down in the brain. It is not known whether using HIV drugs that get into the brain helps reduce symptoms of milder neurological problems. Research studies have had mixed results.

WHAT ARE THE SIGNS OF CNS PROBLEMS? Some neurologic problems require urgent medical attention. If you have serious headaches, especially with a fever, stiff neck, vomiting, or vision problems, or if you develop new weakness or loss of feeling, you should see your health care provider immediately. The main symptoms of nervous system problems are with thinking, behavior, and movement.

Thinking: memory loss, trouble concentrating, mental slowing, trouble understanding. This can include forgetting telephone numbers that you use a lot, having trouble with simple math like making change at the store, People with CNS problems may have difficulty taking their medications on schedule (adherence, see fact sheet 405.) Behavior: Depression, agitation, lack of caring, irritability

Movement: Balance problems, unsteady walking, slower movement, poor coordination, tremor

A physical examination may show reduced reflexes in the ankles, especially when compared to reflexes in the knees. Magnetic Resonance Imaging (MRI,) a radiologic procedure, may show abnormalities in brain tissue.

WHAT MAKES NERVOUS SYSTEM PROBLEMS WORSE? Many factors can contribute to nervous system problems. These include severe depression, drug and alcohol use, infection with hepatitis C (see fact sheet 507), inflammation and normal aging. In addition, CNS problems seem to be more common in people with CD4 cell counts (see fact sheet 124) below 200, either currently or when they were at their lowest. As people with HIV are living longer, aging is also contributing to nervous system problems. Some of the problems of aging may show up faster in people with HIV.

HOW ARE CNS PROBLEMS TREATED? If the side effects of medications include nervous system problems, they usually go away if you stop taking the drugs. This may take as long as several months. People with CNS problems may have problems with taking their medications on schedule (adherence, see fact sheet 405.) They may need extra help remembering to take their medications. Several other neurological problems are emerging in people, even those taking antiviral medications. This includes conditions related to immune reconstitution inflammatory syndrome (IRIS, see fact sheet 483).

THE BOTTOM LINE

HIV disease can cause a wide range of nervous system problems, from forgetfulness and balance problems to serious dementia. These problems usually dont show up until the later stages of HIV disease. However, problems with memory can show up even in people with no other symptoms. The new combination therapies that fight HIV seem to protect the central nervous system against the worst damage from the virus. However, because so many more people with HIV are living longer, and getting older, more nervous system problems are showing up. Caring for someone with serious nervous system problems is very difficult. Caregivers need to take care of themselves, too, to avoid burnout and depression. WHAT IS HEPATITIS? Hepatitis means an inflammation, or swelling, of the liver. Viruses can cause hepatitis. Alcohol, drugs (including prescription medications), or poisons can also cause hepatitis. So can opportunistic infections such as Mycobacterium Avium Complex (MAC, see fact sheet 514) or Cytomegalovirus (CMV, see fact sheet 504). Hepatitis is a very common disease. It can affect people even if their immune systems are healthy. Hepatitis can lead to serious scarring (cirrhosis) of the liver and liver failure, which can be fatal. Many cases of hepatitis arent treated because people either dont feel sick at all, or think they have the flu. The most common symptoms are loss of appetite, fatigue, fever, body aches, nausea and vomiting, and stomach pain. Some people may have dark urine, light-colored bowel movements, and a yellowing of the skin or of the eyes (jaundice). Your health care provider will check your blood to see if your liver is working normally. These liver function tests measure the amounts of certain chemicals: bilirubin, AST, and ALT (or SGOT and SGPT). High blood levels can be a sign of hepatitis. See fact sheet 122 for more information on liver function tests. Blood tests also look for the viruses that can cause hepatitis. Testing for hepatitis is recommended for all HIV+ people. If you have hepatitis and your health care provider wants to see if your liver is damaged, they might order a biopsy. In this test, a sample of the liver is taken with a needle and tested for signs of infection and scarring (cirrhosis.)

VIRAL HEPATITIS Scientists know about five viruses that can cause hepatitis. They are called hepatitis A, B, C, D, E, and G viruses, or HAV, HBV, and so on. Over 90% of cases of hepatitis are caused by hepatitis A, B, or C.

Viral hepatitis can be acute or chronic. Acute means that the disease only lasts for a few weeks or months. Then the body gets rid of the infection. You may feel sick for a couple of weeks. Chronic hepatitis means that the liver might be inflamed for six months or more. Chronic hepatitis stays in your body. You can infect other people, and your disease can become active again. Hepatitis A and E are both acute diseases. They are spread by contact with fecal matter, either directly or from water that has sewage in it, or through food handled by someone with contaminated hands. Hep A and Hep E do not cause chronic illness. Hepatitis B is the most common hepatitis virus. It can be transmitted from mother to infant, through sexual contact, or through contact with infected blood. Globally, about 10% of people with HIV also are infected with hepatitis B (HBV.) People with HIV are much more likely to develop chronic HBV. Hepatitis B is more serious in people with HIV, but some HIV drugs (3TC, tenofovir, emtricitabine) fight HIV and HBV. For more information, see the Treatment Action Group's Guide to Hepatitis B at http://www.treatmentactiongroup.org/hcv/publications/2009/hbv-guide Hepatitis C is usually spread by direct contact with blood, usually through sharing needles and other injection equipment. Although it doesnt happen as often, some peopleespecially HIV+ MSMhave gotten HCV from unprotected sex. About 75-85% of people infected with HCV develop chronic hepatitis. Hepatitis C can be very mild or show no symptoms, but over 15-50 years, can cause serious liver damage in about 20% of people. .HIV worsens hepatitis C. See Fact Sheet 507 for more information on hepatitis C and HIV. Hepatitis D only shows up in people who get hepatitis B. People who get type D get sicker than people who just have type B. The best way to prevent viral hepatitis is through cleanliness and by avoiding contact with blood. You may not know if someone else is infected. Condoms can help prevent transmission of hepatitis B and C. Also, there are vaccines that can protect you against developing hepatitis A and B, even if youve already been exposed to them. These vaccines may not work for people with CD4 counts below 350. There are no treatments for hepatitis A and E, but they usually only last a couple of weeks. Pegylated interferon and three drugs used against HIV - lamivudine (3TC), tenofovir (TDF) and emtricitabine (FTC) - help treat hepatitis B and D. In September 2002, adefovir dipivoxil (Hepsera) was approved in the US to treat hepatitis B, Tenofovir was approved in August of 2008 and is a better treatment for hepatitis. Fact sheet 507 has more information on drug treatments for hepatitis C. Several drugs are being developed to treat HCV.

OTHER TYPES OF HEPATITIS Hepatitis caused by alcohol, drugs, or poisons leads to the same symptoms as viral hepatitis. In these cases, the liver is not damaged by a viral infection. The job of the liver is to break down many substances in the blood, and it can get overloaded. Some medications used to fight AIDS or related diseases can cause hepatitis. So can the common painkiller, acetaminophen (Tylenol). The best treatment for these types of hepatitis is to stop using alcohol or the drugs that are irritating the liver. If hepatitis is caused by an opportunistic infection (OI) related to AIDS, then the OI has to be controlled so that the liver can heal.

MEDICATION PROBLEMS The liver needs to be working properly to break down most drugs. Drugs that didnt cause you any problems when your liver was healthy can make you very sick if you have hepatitis. This is also true for alcohol, aspirin, herbs, and recreational drugs. Be sure your health care provider knows about all pills or supplements you are taking. Some medications to treat hepatitis interact with antiretroviral medications. Your health care provider will have to check carefully to see which drugs can be taken at the same time.

ALTERNATIVE APPROACHES Two herbs seem to help with any form of hepatitis. One is licorice (Glycyrrhiza glabra), often taken as capsules or as a tea. The other is milk thistle (Silybum marianum, see Fact Sheet 735), used as an extract or a tea. Be sure to talk with your health care provider or an experienced herbalist before using licorice or milk thistle. WHAT IS HEPATITIS C? The hepatitis C virus can cause liver damage. Hepatitis C (HCV) is transmitted primarily by direct blood-to-blood contact. Most people get HCV through injection drug use with shared equipment. Up to 90% of people who have ever injected drugs, even just once, have been infected with HCV. Some people have gotten HCV from unprotected sex. This is particularly true for HIV-infected men who have sex with men, people with other sexually transmitted diseases, people with multiple sexual partners, and those who engage in sexual activities that

cause bleeding, such as fisting. Tattooing can cause infection. Some people get infected in medical settings, through accidental needle sticks or unsterilized equipment. The risk from blood transfusions and blood products in the US is virtually zero. HCV spreads more easily than HIV through contact with infected blood. In the US, about 4 times as many people have HCV as have HIV. You could be infected with HCV and not know it. About 15% to 30% of people clear HCV from their bodies without treatment. The rest develop chronic infection, and the virus stays in their body unless it is successfully treated. HCV might not cause any problems for about 15 to 20 years, or even longer, but it can cause serious liver damage, called cirrhosis. People with cirrhosis are at risk for liver cancer, liver failure, and death. A large study in 2011 found that having chronic hepatitis C doubled the risk of death from any cause.

HOW IS IT DIAGNOSED? Some people with HCV have high levels of liver enzymes. See Fact Sheet 122 for more information on these tests. If you have been at risk for HCV, get tested even if your liver enzyme levels are normal. HCV testing is recommended for all people with HIV, since having both viruses, called coinfection, is common. Usually, the first blood test for HCV is an antibody test. A positive result means that you have been infected with HCV. However, some people recover from HCV without treatment, so you need a HCV viral load test to know if you have chronic infection. Hep C viral load testing is recommended if you have been at risk for HCV or have any signs or symptoms of hepatitis. Hep C tests are similar to the HIV antibody test (see Fact Sheet 102) and viral load tests (see Fact Sheet 125.) Unlike HIV viral loads, HCV viral loads are usually much higher; often in the millions. Unlike HIV, the HCV viral load does not predict disease progression. Hep C viral load or liver enzyme levels cannot tell how damaged your liver is. A liver biopsy is the best way to check the condition of the liver. See Fact Sheet 672 for more information. If there is very little liver damage, some experts recommend monitoring; if there is damage (scarring,) HCV treatment may be necessary.

HOW IS HEP C TREATED?

Almost all cases of HCV could be cured if treatment with interferon was started very soon after infection. Unfortunately most people dont have any signs of hepatitis, or can mistake them for the flu. Most cases are not diagnosed until years later. The first step in treating HCV is to find out which genotype of HCV you have (see fact sheet 674.) Most people with HCV in the US have genotype 1. Genotypes 1 and 4 are harder to treat than genotypes 2 or 3. The usual treatment for HCV has been a combination of two drugs, pegylated interferon (pegIFN) and ribavirin (RBV). Fact Sheet 680 has more information on these two drugs. pegIFN is injected once a week. RBV is a pill taken twice daily. These drugs have some serious side effects, including flu-like symptoms, irritability, depression, and low red blood cell counts (anemia) or white blood cell counts (neutropenia.) Talk with your health care provider about how to deal with side effects. New treatments for HCV are being developed. At present, these drugs are added to pegIFN/RBV. See fact sheet 682 for more information on telaprevir (Incivek) and fact sheet 683 on boceprevir (Victrelis). HCV treatment does not work for everyone, and some people cant tolerate the side effects. People do better if they:

Have type 2 or 3 HCV Start with a lower HCV viral load Do not have serious liver damage Are women Are younger than age 40 Do not have HIV or hepatitis B infection Are white, not African American

CAN HEP C BE PREVENTED? Although there are vaccines to protect you from getting infected with Hep A or Hep B, there is no vaccine yet for Hep C. The best way to prevent Hep C infection is to avoid being exposed to blood that is infected with Hep C. If you dont share equipment to use drugs and avoid other contact with the blood of people infected with Hep C, your risk of Hep C infection will be lower.

HEP C AND HIV TOGETHER

Because HIV and HCV are both spread by contact with infected blood, many people are coinfected with both viruses. HIV increases liver damage from HCV. Coinfected people are more likely to have liver problems from anti-HIV drugs, but your health care provider can choose drugs that easier on the liver.

Coinfection is linked to faster HCV disease progression, and a greater risk of severe liver damage. On the other hand, HCV does not seem to speed up HIV disease progression. Coinfected people are more likely to have liver problems from anit-HIV drugs, but your health care provider can choose drugs that are easier on the liver. People with both infections are more likely to be depressed. Depression is a symptom of HCV. This can cause missed doses of medications (poor adherence, see Fact Sheet 405) and problems thinking (see Fact Sheet 505.) HIV positive people with less than 200 CD4 cells are at highest risk for serious liver damage from HCV. Coinfected people usually have higher HCV viral loads, which means that treatment may be less likely to work. Hep C treatment is less effective for coinfected people. Cure rates are about 20% with type 1 and 50-70% with types 2 or 3. If someone meets the guidelines for HIV treatment their HIV should be treated first. Leaving HIV untreated for 6 to 12 months could have serious consequences. However, sometimes HCV should be treated first. If HIV doesnt need to be treated yet (if CD4 cell counts are high enough, and HIV viral load is low enough), its a good idea to treat HCV first. Then the liver can be in better condition to deal with HIV drugs. Some HIV drugs must be avoided during HCV treatment. Do not use didanosine (ddI) with RBV. Avoid retrovir (AZT) during HCV treatment because it increases the risk for anemia. If you are coinfected, be sure your health care provider knows how to treat both diseases.

WHAT IS HERPES?

Herpes simplex refers to a group of viruses that infect humans. Like herpes zoster (shingles, see Fact Sheet 509), herpes simplex causes painful skin eruptions. Itching and tingling are usually the first signs, followed by a blister that breaks open. The infection stays dormant in nerve cells. This is called "latency." However, it can become active again with no warning. Herpes can be active without symptoms or visible signs. Herpes simplex virus 1 (HSV1) is the common cause of cold sores (oral herpes) around the mouth. HSV2 normally causes genital herpes. However, through sexual activity, HSV1 can cause infections in the genital area, and HSV2 can infect the mouth area. HSV is a very common disease. Approximately 45 million people in the US have HSV infection about one in five people over the age of 12. The US Center for Disease Control estimates that

there are 1 million new genital herpes infections each year. The rates of HSV infection have increased significantly in the past ten years or so. About 80% of people with HIV are also infected with genital herpes. HSV2 infection is more common in women. It infects about one out of four women and about one out of five men. Genital HSV can cause potentially fatal infections in babies. If a woman has active genital herpes at delivery, a cesarean delivery is usually performed. Repeat outbreaks of HSV may occur even in people with normal immune systems. Prolonged herpes outbreaks may be a sign of a weakened immune system. This includes people with HIV disease, especially those over 50 years old. Fortunately, prolonged outbreaks that fail to heal are rare except in people with HIV with very low CD4+ cell counts. Also, they have become very uncommon since the introduction of more effective antiretroviral treatments in the 1990s.

HSV AND HIV HSV is not one of the infections that are part of the official diagnosis of AIDS. However, people infected with both HIV and HSV are likely to have more frequent outbreaks of herpes. These outbreaks can be more serious and last longer than for people without HIV. Herpes sores provide a way for HIV to get past the bodys immune defenses and make it easier to get HIV infection. A recent study found that people with HSV had three times the risk of becoming infected with HIV as people without HSV. A recent study found that treating HSV can lead to a significant reduction in HIV viral load. However, another study found that treating genital herpes did not prevent new HIV infections. People with both HIV and HSV also need to be very careful during outbreaks of HSV. Their HIV viral load (see Fact Sheet 125 on viral load) usually goes up, which can make it easier to transmit HIV to others. On the other hand, treatment of HSV in people with both HIV and HSV can reduce HIV viral load. It might also reduce the risk of transmitting HIV to others.

HOW IS HSV TRANSMITTED? HSV infections are passed from person to person by direct contact with an infected area. You dont have to have an open HSV sore to spread the infection!

Also, most people with HSV dont know that they are infected and arent aware that they could be spreading it. In fact, in the US, only about 9% of people with HSV2 infection knew that they had it.

HOW IS HERPES TREATED?

The standard treatment for HSV is the drug acyclovir, given orally (in pill form) from two to five times a day. Another form of acyclovir is valacyclovir. It can be taken just two or three times a day, but it is much more expensive than acyclovir. Famciclovir is another drug used to treat HSV. In 2011 there were several reports that using acyclovir or valacyclovir reduced HIV viral load and slowed disease progression. These drugs do not cure HSV infections. However, they can make the outbreaks shorter and less severe. Doctors may prescribe maintenance therapy daily anti-herpes medications for people with HIV who have had repeated outbreaks. Maintenance therapy will prevent most outbreaks. It also significantly decreases the number of days each month when HSV can be detected on the skin or mucous membranes, even when there are no symptoms.

CAN HERPES BE PREVENTED? It is difficult to prevent the spread of HSV. Partly this is because most infected people dont know that they carry HSV and can spread it. Even people who know they are infected with HSV may not realize they can transmit the infection even without an open herpes sore. Condoms can reduce the rate of HSV transmission. However, they cannot prevent it. HSV infections can be transmitted to and from a larger genital area, such as that area covered by boxer shorts and also around the mouth. If people with herpes take valacyclovir every day, they can reduce the risk of transmitting herpes to others. Once-daily valacyclovir is approved for people without HIV who have up to 9 outbreaks a year. However, once-daily therapy is less effective in people with HIV and others with very frequent episodes. Drug companies are working on vaccines to prevent HSV. One vaccine showed good results against HSV2 in women, but not in men. No vaccines have been approved yet to prevent HSV infection, but research is ongoing in this area.

THE BOTTOM LINE Herpes simplex is a viral infection that can cause genital herpes or cold sores around the mouth. Most people infected with HSV dont know it. HSV is transmitted easily from person to person during sexual activity or other direct contact with a herpes infection site. Herpes can be transmitted even when there is no visible open sore. There is no cure for herpes. It is a permanent infection. People with herpes have occasional outbreaks of painful blisters. When each outbreak ends, the infection becomes latent for a while. People with HIV have more frequent and more serious outbreaks of HSV.

WHAT IS SHINGLES? Shingles is a very painful disease caused by the same herpes virus that causes chickenpox (varicella zoster virus). Like other herpes viruses, the varicella-zoster virus has an initial infectious stage (chickenpox) followed by a dormant stage. Then, with no warning, the virus becomes active again.About 20% of people who have had chickenpox will eventually develop shingles. This reactivation of the virus is most likely to occur in people with a weakened immune system. This includes people with HIV disease, and anyone over 50 years old. Herpes zoster lives in nerve tissue. Outbreaks of shingles start with itching, numbness, tingling or severe pain in a belt-like pattern on the chest, back, or around the nose and eyes. In rare cases, herpes can infect the facial or eye nerves. This can cause outbreaks around the mouth, on the face, neck, and scalp, in and around the ear, or at the tip of the nose. Shingles outbreaks are almost always on just one side of the body. Within a few days, a rash appears on the skin area related to the inflamed nerve. Small blisters form and fill with fluid. Later they break open and develop crusty scabs. If the blisters are scratched, someone with shingles might develop a skin infection. This could require treatment with antibiotics and might cause scars. In most cases, the rash goes away within a few weeks, but in some cases, severe pain can last for months or even years. This condition is called post herpetic neuralgia.

SHINGLES AND HIV Shingles is not one of the infections that leads to a diagnosis of AIDS. Shingles can occur in people with HIV shortly after they start taking strong antiretroviral medications. These cases of shingles are believed to be a sign of immune restoration syndrome (see Fact Sheet 483). A recent study found that A CD4 cell count (see fact sheet 124) below 500 and a detectable viral load (see fact sheet 125) are risk factors for shingles in people with HIV. Having HIV increases the risk of complications from shingles. These include pain (post herpetic neuralgia.) Also, if you notice any blurred vision, see your health care provider immediately. Also, as more people with HIV reach higher ages, they may be more likely to develop shingles.

HOW IS IT TRANSMITTED? Shingles can only occur after someone has had chickenpox. If someone who has already had chickenpox comes into contact with the fluid from shingles blisters, they will not catch shingles. However, people who have not had chickenpox could become infected with herpes zoster and develop chickenpox. They should avoid contact with the shingles rash or with anything that may have touched the shingles rash or blisters.

HOW IS SHINGLES TREATED? Several types of drugs are used to treat shingles. They include anti-herpes drugs and several types of treatment for pain. Antiviral drugs: The standard treatment for shingles is the drug acyclovir, which can be given orally (in pill form) or intravenously in more severe cases. Two newer drugs have been approved for the treatment of shingles: famciclovir and valacyclovir. Both famciclovir and valacyclovir are taken three times each day, compared to five times for acyclovir. All of these drugs work best when they are started within the first three days after the shingles pain begins. Nerve blockers: Health care providers often prescribe various pain medications for people with shingles. Because the pain of shingles can be so intense, researchers have looked for other ways to block the pain. Injections of anesthetic drugs and/or steroids are being studied as nerve

blockers. These can be injected either into peripheral nerves, or into the spinal column (central nervous system). Skin Treatments: Several creams, gels and sprays are being studied. These provide temporary relief from pain. Capsaicin, the chemical that makes chili peppers hot, has shown good preliminary results. In addition, in 1999 the FDA approved a patch form of the anesthetic lidocaine. The patch, called Lidoderm, provides pain relief for some people with shingles. Because it is applied to the skin, it has less risk of side effects than pain medications taken in pill form. A newer skin treatment is Qutenza. It is a highly concentrated form of capsaicin. It is applied in a doctors office for 60 minutes. One application can provide 3 months of relief. Other Pain Medications: Some drugs normally used to treat depression, epilepsy, or severe pain are sometimes used for the pain of shingles. These can have a variety of side effects. Nortriptyline is the antidepressant most frequently used for shingles pain. Pregabalin is an epilepsy medicine also used for pain after shingles.

CAN SHINGLES BE PREVENTED? Currently, there is no way to predict an outbreak of shingles. Researchers have shown that giving older people a stronger form of the chickenpox vaccine used for children can boost the type of immunity believed necessary to hold the virus in check. Zostavax, a shingles vaccine developed by Merck, has been approved by the FDA. An initial study in people with HIV showed that Zostavax was safe and effective.

THE BOTTOM LINE Shingles is an unpredictable, very painful disease. It is caused by a re-activation of the virus that causes chickenpox. Although not directly linked to HIV, shingles seems to occur more frequently in people with AIDS. Although shingles may disappear within a couple of weeks, severe pain may continue for several months. A shingles vaccine has been approved by the FDA. An initial study in people with HIV found that Zostavax was safe and effective.

The disease has been treated with acyclovir, taken five times daily, or given intravenously in severe cases. Two newer drugs, famciclovir and galaciclovir, seem to be more effective against the pain of shingles and need to be taken only three times each day. It can be very difficult to deal with the pain of shingles. A newer treatment is an anesthetic patch that can be applied directly to the skin. WHAT IS HPV? There are over 100 viruses known as human papilloma virus (HPV). They are common. One study found HPV in 77% of HIV-positive women. HPV is transmitted easily during sexual activity. It is estimated that 50% of all sexually active people get at least one type of HPV infection. Some types of HPV cause common warts of the hands or feet. Infections of the hands and feet are usually not transmitted through sexual activity. Several types of HPV cause genital warts on the penis, vagina, and rectum. Those with HIV can get worse sores in the rectum and cervical area. HPV can also cause problems in the mouth or on the tongue or lips. Other types of HPV can cause abnormal cell growth known as dysplasia. Dysplasia can develop into various cancers in men and women. Dysplasia around the anus is called anal intraepithelial neoplasia (AIN). Anal intraepithelial neoplasia is the development of new abnormal cells in the lining of the anus. Dysplasia in the cervical region is called cervical intraepithelial neoplasia (CIN). AIN or CIN appear to be more common in people with HIV infection than those who are HIV negative.

HOW IS HPV DETECTED? Many people have HPV infections but don't know it. HPV can go away without causing any problems. To detect HPV, health care providers look for dysplasia or genital warts. A Pap test (or smear) is used to check a woman's cervix. It can also be used to check the anus of men and women. They are smeared on a glass slide or mixed into liquid and examined under a microscope. The cells are examined for abnormalities that may indicate abnormal cell changes, such as dysplasia or cervical cancer. In 2009 the FDA approved two tests that use the sample collected by a Pap test. These tests look for types of HPV that are linked to health problems. Dysplasia can be detected by Pap smears.

Some researchers believe that anal and cervical smears should be checked each year for people with elevated risk:

People who have had receptive anal intercourse Women who have had cervical intraepithelial neoplasia (CIN) Anyone with under 500 CD4 cells.

However, other researchers think that careful physical examination can detect as many cases of anal cancer as anal Pap testing. Genital warts can appear anywhere from a few weeks to a few months after you are exposed to HPV. The warts might look like small bumps. Sometimes they are fleshy and look like small cauliflowers. They can get bigger over time. Your health care provider can usually tell if you have genital warts by looking at them. Sometimes a tool called an anoscope is used to look at the anal area. If necessary, a sample of the suspected wart will be cut off and examined under a microscope. This is called a biopsy. Genital warts are not caused by the same HPV that causes cancer. However, if you have warts, you may have also been exposed to other types of HPV that could cause cancer.

CAN HPV INFECTION BE PREVENTED? There is no easy way to tell if someone is infected with an HPV. People who dont have any signs or symptoms of HPV infection can transmit the infection. Condoms do not totally prevent transmission of HPV. HPV can be transmitted by direct contact with infected areas that arent covered by a condom. Men and women with HIV who are sexually active may want to have a regular Pap smear, anal and/or vaginal, to check for abnormal cells or early signs of warts. A positive result can be followed up to see if treatment is needed. Two vaccines have been approved for use by men and women ages 9 to 26. The vaccine is given as a series of three injections over 6 months. They work best in people who have not yet been sexually active. They have not been tested in or approved for people already infected with HPV. For more information on vaccination against HPV, see http://www.immunize.org/vis/hpv.pdf. In 2011, the US Centers for Disease Control recommended that all boys be vaccinated against HPV at the age of 11 years.

HOW ARE HPV INFECTIONS TREATED? There is no direct treatment for HPV infection. Some people clear an HPV infection (are cured). They can later be infected with HPV again. Dysplasias and warts can be removed. There are several ways to do this:

Burning them with an electric needle (electrocautery) or a laser Freezing them with liquid nitrogen Cutting them out Treating them with chemicals. Trichloroacetic acid (TCA) is effective for some people.

Other, less common treatments for warts include the drugs 5-FU (5-fluorouracil) and Interferonalpha. A new drug, imiquimod (Aldara), has been approved for treatment of genital warts. Cidofovir (Vistide), originally developed to fight cytomegalovirus (CMV), might also help fight HPV. HPV infection can last for a long time, especially in people who are HIV-positive. tA 2012 study found that a high proportion of cases of anal cancer are found among HIV-positive men. Dysplasia and warts can return. They should be treated as soon as they are found to reduce the chances of the problem spreading or returning.

THE BOTTOM LINE Human papilloma viruses (HPV) are fairly common. Different types of HPV cause warts or abnormal cell growth (dysplasia) in or near the anus or cervix. This abnormal cell growth can result in cervical or anal cancer. Genital HPV infections are transmitted through sexual activity. HPV infection can last a long time, especially in people with HIV. A Pap smear can detect abnormal cell growth in the cervix. It can also be used to check the anus of men and women. Although Pap smears may be the best way to detect early cervical cancer, careful physical examination may be the best way to detect anal cancers. The signs of HPV infection warts or dysplasia should be treated as soon as they show up. Otherwise, the problem could spread and be more likely to return after treatment. For more information, see the web site http://www.thehpvtest.com/

WHAT IS KS? Kaposis sarcoma (KS) is a cancer-like disease. It originally was known as a disease affecting elderly men of Eastern European or Mediterranean background. KS also occurs in African men and people with a weakened immune system. The most common cause of KS now is HIV infection. KS is a sign of AIDS. KS usually shows up in the skin, or in the linings of the mouth, nose, or eye. KS can also spread to the lungs, liver, stomach and intestines, and lymph nodes. KS involves the development of many new, tiny blood vessels. This process is called angiogenesis. KS is caused by a herpes virus called Human Herpes Virus 8 (HHV-8). In a recent study, men with HHV-8 were nearly 12 times more likely to be diagnosed with KS than men who did not have HHV-8 KS affects about 20% of people with AIDS who arent taking anti-HIV drugs. The rate of KS has dropped by over 80%since the introduction of strong antiretroviral therapy (ART). However, in 2007, scientists reported finding new cases of KS in people whose HIV is under control. These new cases seem to be mild and not life-threatening. KS is mostly a disease of men: there are at least 8 men with KS for each woman. It is one of the most visible signs of AIDS, because it usually shows up as spots on the skin (lesions) that look red or purple on white skin, and bluish, brownish or black on dark skin. Lesions often occur on the face, arms and legs. KS on the skin is not life threatening. However, KS lesions on the feet and legs can make it difficult to walk. If KS spreads to other parts of the body, it can cause serious problems. In the mouth lining, it can cause trouble eating and swallowing. In the stomach or gut, it can cause internal bleeding and blockages. If KS blocks lymph nodes, it can cause severe swelling of the arms, legs, face, or scrotum. The most serious form of KS is in the lungs, where it can cause a serious cough, shortness of breath, or an accumulation of fluid that can be fatal. KS can often be diagnosed by looking at the skin lesions. They are usually flat, painless, and do not itch or drain. They can look like a bruise, but a bruise will lose its purple color if you push on it; a KS lesion wont. KS lesions can grow into raised bumps or patches and grow together. Your health care provider might take a small sample (a biopsy) from skin spots to examine under a microscope and confirm a diagnosis of KS.

HOW IS KS TREATED?

Strong ART is the best treatment for active KS. In many people, ART can stop the growth or even clear up skin lesions. In addition to ART, there are different treatments for KS in the skin or in other parts of the body. In the skin, KS may not have to be treated if there are only a few lesions. Skin lesions can be:

Frozen with liquid nitrogen, Treated with radiation, Cut out surgically, Injected with anti-cancer drugs or interferon alpha. Treated with Panretin gel (retinoic acid)

These treatments only deal with the skin lesions, not with KS overall. Skin lesions may come back after treatment. If KS has spread into internal organs, systemic (whole-body) drug treatment is used. If ART is not enough, the drugs doxorubicin (Doxil,) daunorubicin (DaunoXome) or paclitaxel (Taxol) may be added. Doxil and DaunoXome are anti-cancer drugs in liposomal form. Liposomal means that tiny amounts of drug are encased in small fat bubbles (liposomes). The drugs last longer in this form and seem to move to the areas where theyre needed. Some side effects are reduced with liposomal forms of drugs.

CAN KS BE PREVENTED? It is not clear how HHV-8 spreads. It might be spread through sexual activity and deep kissing. As with other opportunistic infections, a healthy immune system can control HHV-8 infection. The best way to prevent KS is by using strong anti-HIV medications to keep your immune system strong.

WHAT ELSE IS BEING STUDIED FOR KS? Anti-cytokine approaches: There is a lot of research on cytokines, proteins that the immune system uses to stimulate cells to grow. Researchers think that substances that can inhibit these (and similar) growth factors can also slow down the growth of KS.

Monoclonal antibodies: These drugs are produced through genetic engineering. Their names end in -mab, such as bevacizumab. Other drugs: Scientists are studying several drugs that slow down the development of new blood vessels (angiogenesis.)

THE BOTTOM LINE KS is a disease that affects up to 20% of people with AIDS who are not taking ART. It is partly caused by a herpes virus called HHV-8. The best treatment for KS is strong antiretroviral therapy (ART.) KS in the skin can be treated in several ways and is not a serious problem. KS in internal organs can be life threatening. Internal KS is usually treated with anti-cancer drugs. If you notice new dark spots on your skin, have your health care provider look at them to see if you might have KS.

WHAT IS LYMPHOMA? Lymphoma is a cancer of white blood cells called B-lymphocytes, or B-cells. They multiply rapidly and form tumors. Lymphoma of the brain or spinal cord is called central nervous system (CNS) lymphoma. AIDS-related lymphoma is sometimes called Non-Hodgkins Lymphoma (NHL). In 1985, the Centers for Disease Control added NHL to the list of diseases that define AIDS. Hodgkins Disease, another type of lymphoma, is rare in people with HIV. The longer you live with a suppressed immune system, the higher the risk of NHL. It can occur even with a high CD4 count. It can be serious and often fatal, sometimes within a year. The use of combination antiretroviral therapy (ART) cut the rates of most opportunistic infections by about 80%. At first, this did not appear to be true for NHL. However, newer studies show a decrease of about 50% in NHL rates, especially CNS lymphoma. NHL still accounts for about 20% of the deaths of people with HIV. Approximately 10% of people with HIV may eventually develop NHL.

HOW IS NHL DIAGNOSED?

NHL tumors can occur in the bone, abdomen, liver, brain or other parts of the body. The first signs of NHL are swollen lymph nodes, fever, night sweats, and weight loss of more than 10%. These symptoms occur with several AIDS-related illnesses. If health care providers cannot find another cause for these symptoms, they will test for NHL. NHL is usually diagnosed using imaging techniques or biopsies. The imaging techniques include various scans (CAT, PET, gallium, and thallium). A biopsy is an examination of cells from a suspected tumor. The cells are collected by a thin needle, or they are cut out surgically.

WHAT CAUSES NHL? NHL is caused by long-term stimulation of the immune system. When B-cells multiply quickly for many years, more mutations occur. Some of these mutations cause cancer. About 4% of people with symptoms of HIV disease develop NHL each year. The rate of NHL in people with HIV is over 80 times higher than for the general population. A recent study found higher rates for people with a CD4 count that ever dropped below 200, and the longer they had a high or uncontrolled viral load. The risk of NHL is increased by infection with Epstein-Barr virus and by genetic factors. The rate of NHL is twice as high in men as in women, and twice as high in Caucasians as in people of African or Caribbean ancestry. At the present time we dont know how to prevent NHL.

HOW IS NHL TREATED? Most cancers are treated by a combination of drugs (chemotherapy or chemo). Chemo is very toxic. It suppresses the immune system. It can cause nausea, vomiting, fatigue, diarrhea, swollen and sensitive gums, mouth sores, hair loss, and numbness or tingling in the feet or hands. Chemo also damages bone marrow. This can cause anemia (low red blood cells) and neutropenia (low white blood cells). Neutropenia increases the risk of bacterial infections. Additional drugs may be needed to fight these side effects. NHL in the central nervous system is very difficult to treat. Radiation therapy may be used instead of, or in addition to chemotherapy. ART makes it easier for HIV patients to tolerate strong chemotherapy for NHL. As a result, the death rate from NHL has dropped by over 80%. Seventy-four percent of patients recovered from NHL in a study using a newer combination of chemotherapy drugs known as EPOCH.

Since people started using strong ART, the types of NHL seen in people with HIV are easier to treat. As a result, people with HIV and NHL are living longer. Several types of chemo are used for NHL. Chemo clears up tumors in about 50% of patients. However, tumors return in many patients within a year. People diagnosed with NHL are at a higher risk of developing pneumocystis pneumonia (PCP) and should take medications to prevent it. See Fact Sheet 515 for more information on PCP. Monoclonal antibodies are being used against NHL, and researchers continue to study their use. These drugs are produced through genetic engineering. They attack the B-cells that are multiplying out of control. The names of monoclonal antibodies end in -mab, such as rituximab. They shrink tumors and increase the time before tumors return.

THE BOTTOM LINE NHL, a cancer involving B-cells, affects people with advanced AIDS. It is serious and often fatal. The use of ART has reduced the number of new cases. This is especially true for NHL in the central nervous system (CNS). NHL is treated with chemotherapy drugs. In the CNS, radiation therapy is also used. Even if NHL tumors are cleared up, they tend to return in many people. Treatment of NHL is difficult. People who get it often have very weak immune systems. ART strengthens the immune system and permits the use of stronger chemotherapy. It also seems to make NHL easier to treat. Additional drugs are often needed to deal with the side effects of chemo. New genetically engineered drugs called monoclonal antibodies are now being used against NHL. Studies of the use of monoclonal antibodies and new combinations of chemo drugs are continuing.

WHAT IS MOLLUSCUM? Molluscum contagiosum is a skin infection. It is caused by a virus. Molluscum causes small bumps (lesions) to appear on the skin. Most of them are less than half an inch in diameter. They have a hard white core. Some lesions have a small dent or dimple in the center. The lesions are the same color as normal skin, but they look waxy. They usually dont hurt or itch.

The molluscum virus is very common, and almost everyone has it in his or her body. A healthy immune system will control molluscum so that if lesions appear, they do not last a long time. People with weakened immune systems can develop molluscum lesions that spread, last a long time, and are very difficult to treat. About 20% of people with AIDS will develop molluscum. Molluscum is not a serious health problem. However, many people find the molluscum lesions to be very unattractive. This can cause serious emotional or psychological problems.

HOW DOES MOLLUSCUM SPREAD? Molluscum can be spread by direct skin contact. It often spreads through sexual activity. Molluscum can infect any part of the skin, but it is especially common on the face or in the groin and pubic areas. It can be spread from existing lesions to other parts of the body or to other people. It can also be spread by objects (or clothing) that came in contact with a lesion. Men with HIV often develop molluscum on their face. Shaving with a razor blade can spread it.

HOW DO I KNOW IF I HAVE MOLLUSCUM? A health care provider can easily identify molluscum lesions. They are waxy, flesh-colored bumps that dont hurt or itch. There are only one or two other infections that cause skin problems that look at all similar to molluscum.

HOW IS MOLLUSCUM TREATED? Molluscum lesions are treated the same way as warts. Unfortunately, the lesions often return and need to be treated again.

They can be frozen with liquid nitrogen. This is the most common method of treatment. They can be burned with an electric needle (electrocautery) or a laser. This treatment can be painful and sometimes leaves scars.

They can be treated with chemicals used on warts such as trichloroacetic acid (TCA), podophyllin, or podofilox. These chemicals can not be used on sensitive skin or near the eyes. They can be cut or scooped out surgically. This treatment can be painful and can leave scars. They can be treated with drugs used to treat acne such as tretinoin (Retin-A) or isotretinoin (Accutane). This is a newer approach. These drugs reduce the amount of oil in the skin. The top layer of skin dries out and peels off. These drugs can cause redness and soreness. Retin-A is a cream that is put onto the lesions. Accutane is taken in pill form. Another approach is to use the antiviral medications cidofovir, cantharidin or imiquimod. These drugs are applied directly onto the lesions. They can cause local skin irritation.

CAN MOLLUSCUM BE PREVENTED? Because the virus that causes molluscum is so common, it is not possible to avoid being exposed to it. However, if you have molluscum you should make sure that the lesions dont touch anyone else. You should also be careful not to spread molluscum to different parts of your body. Be careful not to scratch the lesions or to cut them while shaving. Some health care providers think that using an electric shaver helps prevent the spread of molluscum.

DRUG INTERACTION PROBLEMS The acne drugs tretinoin (Retin-A) and isotretinoin (Accutane) tend to dry out the skin. Dry skin is also a side effect of the protease inhibitor indinavir (Crixivan) and some other antiretroviral medications (ARVs). If you take use Retin-A or Accutane to treat molluscum along with ARVs that can cause dry skin, your skin problems could get worse.

THE BOTTOM LINE Molluscum is a viral infection that can produce skin lesions. Although they are not medically dangerous, the lesions can cause serious emotional and psychological problems.

Molluscum can be spread from person to person by direct skin contact. It can be spread during sexual activity. If you have molluscum, you can spread the lesions to new areas if you shave with a blade. Molluscum lesions are removed in the same ways as warts. Unfortunately, they often return and have to be treated again.

WHAT IS MAC? Mycobacterium Avium Complex (MAC) is a serious illness caused by common bacteria. MAC is also known as MAI (Mycobacterium Avium Intracellulare). MAC infection can be localized (limited to one part of your body) or disseminated (spread through your whole body, sometimes called DMAC). MAC infection often occurs in the lungs, intestines, bone marrow, liver, and spleen. The bacteria that cause MAC are very common. They are found in water, soil, dust, and food. Almost everyone has them in their body. A healthy immune system will control MAC, but people with weakened immune systems can develop MAC disease. Up to 50% of people with AIDS may develop MAC, especially if their CD4 cell count is below 50. MAC almost never causes disease in people with more than 100 CD4 cells.

HOW DO I KNOW IF I HAVE MAC? The symptoms of MAC can include high fevers, chills, diarrhea, weight loss, stomach aches, fatigue, and anemia (low numbers of red blood cells). When MAC spreads in the body, it can cause blood infections, hepatitis, pneumonia, and other serious problems. Many different opportunistic infections can cause these symptoms. Therefore, your health care provider will probably check your blood, urine, or saliva to look for the bacteria that causes MAC. The sample will be tested to see what bacteria are growing in it. This process, called culturing, can take several weeks. Even if you are infected with MAC, it can be hard to find the MAC bacteria. If your CD4 cell count is less than 50, your health care provider might treat you for MAC, even without a definite diagnosis. This is because MAC infection is very common but can be difficult to diagnose.

HOW IS MAC TREATED? The MAC bacteria can mutate and develop resistance to some of the drugs used to fight it. Health care providers use a combination of antibacterial drugs (antibiotics) to treat MAC. At least two drugs are used: usually azithromycin or clarithromycin plus up to three other drugs. MAC treatment must continue for life, or else the disease will return. People react differently to anti-MAC drugs. You and your health care provider may have to try different combinations before you find one that works for you with the fewest side effects. The most common MAC drugs and their side effects are:

Amikacin (Amkin): kidney and ear problems; taken as an injection. Azithromycin (Zithromax, see fact sheet 530): nausea, headaches, vomiting, diarrhea; taken as capsules or intravenously. Ciprofloxacin (Cipro or Ciloxan, see fact sheet 531): nausea, vomiting, diarrhea; taken as tablets or intravenously. Clarithromycin (Biaxin, see fact sheet 532): nausea, headaches, vomiting, diarrhea; taken as capsules or intravenously. Note: The maximum dose is 500 milligrams twice a day. Ethambutol (Myambutol): nausea, vomiting, vision problems. Rifabutin (Mycobutin): rashes, nausea, anemia. Many drug interactions. Rifampin (Rifampicin, Rifadin, Rimactane): fever, chills, muscle or bone pain; can turn urine, sweat, and saliva red-orange (may stain contact lenses); can interfere with birth control pills. Many drug interactions.

CAN MAC BE PREVENTED? The bacteria that cause MAC are very common. It is not possible to avoid being exposed. The best way to prevent MAC is to take strong antiretroviral medications (ARVs). Even if your CD4 cell count drops very low, there are drugs that can stop MAC disease from developing in up to 50% of people. The antibiotic drugs azithromycin, rifabutin, and clarithromycin have been used to prevent MAC. These drugs are usually prescribed for people with less than 50 CD4 cells. Combination antiretroviral therapy can make your CD4 cell count go up. If it goes over 100 and stays there for 3 months, it may be safe to stop taking medications to prevent MAC. Be sure to

talk with your health care provider before you stop taking any of your prescribed medications.

DRUG INTERACTION PROBLEMS Several drugs used to treat MAC interact with many other drugs, including ARVs, antifungal drugs, and birth control pills. This is especially true for rifampin, rifabutin, and rifapentine. Be sure your health care provider knows about all the medications that you are taking so that all possible interactions can be considered.

THE BOTTOM LINE MAC is a serious disease caused by common bacteria. MAC can cause serious weight loss, diarrhea, and other symptoms. If you develop MAC, you will probably be treated with azithromycin or clarithromycin plus one to three other antibiotics. You will have to continue taking these drugs for life to avoid a recurrence of MAC. People with 50 CD4 cells or less should talk with their health care providers about taking drugs to prevent MAC.

WHAT IS PCP? Pneumocystis pneumonia (PCP or pneumocystis) is the most common opportunistic infection in people with HIV. Without treatment, over 85% of people with HIV would eventually develop PCP. It has been the major killer of people with HIV. Although PCP is now almost entirely preventable and treatable, it still causes death in about 10% of cases.

Currently, with strong antiretroviral therapy (ART, see fact sheet 403) available, PCP rates have dropped dramatically. Unfortunately, PCP is still common in people who are infected with HIV for a long time before getting treatment. In fact, 30% to 40% of people with HIV develop PCP if they wait to get treatment until their CD4 cell counts are around 50. The best way to reduce cases of PCP is testing for HIV to identify cases sooner. PCP is caused by a fungus. It used to be called pneumocystis carinii, but scientists now call it pneumocystis jiroveci. A healthy immune system can control the fungus. However, PCP causes illness in children and in adults with a weakened immune system. Pneumocystis almost always affects the lungs, causing a form of pneumonia. People with CD4 cell counts (see Fact Sheet 124) under 200 have the highest risk of developing PCP. People with counts under 300 who have already had another opportunistic infection are also at risk. Most people who get PCP become much weaker, lose a lot of weight, and are likely to get PCP again. The first signs of PCP are difficulty breathing, fever, and a dry cough. Anyone with these symptoms should see a health care provider immediately. However, everyone with CD4 counts below 300 should discuss PCP prevention with their health care provider, before they experience any symptoms.

HOW IS PCP TREATED? For many years, antibiotics were used to prevent PCP in cancer patients with weakened immune systems. In 1985 a study showed that these drugs would also prevent PCP in people with AIDS. The drugs used to treat PCP include TMP/SMX, dapsone, pentamidine, and atovaquone. TMP/SMX (Bactrim or Septra, see Fact Sheet 535) is the most effective anti-PCP drug. Its a combination of two antibiotics: trimethoprim (TMP) and sulfamethoxazole (SMX). Dapsone (see Fact Sheet 533) is similar to TMP/SMX. Dapsone seems to be almost as effective as TMP/SMX against PCP. Pentamidine (NebuPent, Pentam, Pentacarinat) (see Fact Sheet 537) is a drug that is usually inhaled in an aerosol form to prevent PCP. Pentamidine is also used intravenously (IV) to treat active PCP. Atovaquone (Mepron) (see Fact Sheet 538) is a drug used in people with mild or moderate cases of PCP who cannot take TMP/SMX or pentamidine. Based on a small study, if standard therapy doesnt work, patients might be able to use Neutrexin (trimetrexate) combined with Leucovorin (folinic acid.)

CAN PCP BE PREVENTED? The best way to prevent PCP is to use strong ART. People who have less than 200 CD4 cells can prevent PCP by taking the same medications used for PCP treatment. Another way to reduce the risk of PCP is not to smoke, or to stop smoking. HIV-positive smokers develop PCP two to three times faster than HIV-positive people who do not smoke. One study found that ex-smokers who stopped for at least a year developed PCP no quicker than nonsmokers. Combination ART can make your CD4 cell count go up. If it goes over 200 and stays there for 3 months, it may be safe to stop taking PCP medications. However, because PCP medications are inexpensive and have mild side effects, some researchers think they should be continued until your CD4 cell count reaches 300. Be sure to talk with your health care provider before you stop taking any of your prescribed medications.

WHICH DRUG IS BEST? Bactrim or Septra (TMP/SMX) is the most effective drug against PCP. It is also inexpensive, costing only about $10 per month. It is taken in pill form, not more than one pill daily. Cutting back from one pill a day to three pills a week reduces the allergy problems of Bactrim and Septra, and seems to work just as well. However, the SMX part is a sulfa drug and almost half of the people who take it have an allergic reaction. This usually is a skin rash, sometimes a fever. Allergic reactions can be overcome using a desensitization procedure. Patients start with a very small amount of the drug and take increasing amounts until they can tolerate the full dose. Dapsone causes fewer allergic reactions than TMP/SMX. It is also fairly inexpensive - about $30 per month. It also is taken as a pill and, like Bactrim or Septra, not more than one pill daily. Pentamidine involves a monthly visit to a clinic with a nebulizer, the machine that produces a very fine mist of the drug. The mist is inhaled directly into the lungs. The procedure takes about 30 to 45 minutes. You pay for the drug plus the clinic costs, between $120 and $250 per month. Patients using aerosol pentamidine get PCP more often than people taking the antibiotic pills.

THE BOTTOM LINE PCP is now almost totally treatable and preventable. However, it is still common in people who do not know they are infected with HIV. Strong antiretroviral drugs (ARVs) can keep the CD4 cell count from dropping. If your CD4 cell count is below 300, talk to your health care provider about taking drugs to prevent PCP. Everyone whose CD4 cell count is below 200 should be taking anti-PCP medication.

WHAT IS PML? Progressive multifocal leucoencephalopathy is a serious viral infection of the brain. Encephalo means brain. Pathy means disease. Encephalopathy is a disease of the brain. Leuco- (or "leuko") means pale or white. Leucoencephalopathy is a disease of the white matter of the brain. Progressive means that this disease gets worse in a short time. Multifocal means that it shows up in several places at the same time. Researchers estimate that about 6% of people with AIDS develop PML. Most cases of PML show up in people with CD4 cell counts below 100. The exact rate is hard to know because PML is difficult to diagnose. Most cases of PML used to be fatal. People diagnosed with PML lived an average of 6 months, and most died within 2 years. However, if people with PML start taking strong antiretroviral medications (ARVs) to control their HIV, they can survive much longer. Now more than half of people with HIV and PML survive for at least two years. The JC virus causes PML. Between 8085% of all adults are exposed to this virus worldwide. In people with weakened immune systems, JC virus can become active.

HOW CAN PML BE DETECTED? The first symptoms of PML are weakness or coordination problems in an arm or leg. There may be difficulty thinking or speaking. Vision and memory problems, seizures, and headaches can occur.

These symptoms can also occur with other opportunistic infections, including toxoplasmosis, lymphoma, inner ear infections, or cryptococcal meningitis. It is important to rule out these other diseases. PML can be diagnosed using a scan of the brain by magnetic resonance imaging (MRI). Another way to test for PML is by checking spinal fluid. The sample is taken by inserting a needle into the spinal canal. This procedure is called a spinal tap.

HOW IS PML TREATED? A major problem with treating any brain infection is the blood-brain barrier. The blood vessels around the brain are different from the rest of the body. They are tightly woven to protect the brain from toxic substances. Chemicals that dissolve in fat can get through. Those that dissolve in water cant. Unfortunately, this includes most antibiotics and many other medications. There is currently no proven treatment for PML. Research studies have had conflicting results. Some possible treatments have not been carefully studied. However, PML has slowed down or stopped in some patients taking strong ARVs to fight HIV.Strengthening the immune system is currently the best way to treat PML. This approach might trigger immune reconstitution inflammatory syndrome (IRIS, see fact sheet 483.) Ara-C (Cytosine arabinoside or cytarabine) has been tried against PML. It was given intravenously, or pumped directly into the brain. It seemed to work in one small study, but not in later ones. Ara-C is very toxic, and damages bone marrow. High-dose AZT has been tried against PML, because it crosses the blood-brain barrier. Other substances that have been tried with different degrees of success include acyclovir, heparin, peptide-T, beta interferon, dexamethasone, mefloquine, n-acetylcysteine, topotecan and cidofovir. Because PML can progress rapidly, it is important to begin treatments quickly.

THE BOTTOM LINE PML is a viral infection of the brain caused by the JC virus. It is fatal in about 50% of cases. It can be confused with other medical conditions.

There is no approved treatment for PML, although several treatments may be helpful. Strengthening the immune system using antiretroviral therapy is currently the best approach. Any treatment must be started as early as possible. Combination antiretroviral therapy (ART) may slow the progress of PML.

WHAT IS TOXOPLASMOSIS? Toxoplasmosis (toxo) is an infection caused by the single-celled parasite toxoplasma gondii. A parasite lives inside another living organism (the host) and takes all of its nutrients from the host. The most common illness caused by toxo is an infection of the brain (encephalitis). Toxo can also infect other parts of the body. Toxo can lead to coma and death. The risk of toxo is highest when your CD4 cell (T-cell) counts are below 100.

HOW COMMON IS TOXO? The toxo parasite is very common in cat feces, raw vegetables, and the soil. It is also common in raw meat, especially pork, lamb, or deer meat. It can get into your body when you breathe in dust. Up to 50% of the population is infected with toxo. A healthy immune system will keep toxo from causing any disease. It does not seem to spread from person to person. In the early years of the HIV epidemic, toxo was a common disease. With better treatments, it has become uncommon. In 1995, 10,000 people were hospitalized for toxo. By 2008 that number dropped to less than 3,000. However, toxo still occurs in people with HIV, especially if they are not tested and receiving medical care. Rates of toxo are higher in blacks and Hispanics than in whites.

HOW IS TOXO DIAGNOSED?

The most common illness caused by toxo is an infection of the brain (encephalitis). Toxo can also infect other parts of the body. Toxo can lead to coma and death. The risk of toxo is highest when your CD4 cell (T-cell) counts are below 100.

The first signs of toxo include fever, confusion, headache, disorientation, personality changes and tremor. Other symptoms include seizures, poor coordination, and nausea. Toxo is usually diagnosed by testing for antibodies to toxoplasma gondii. Pregnant women who are exposed to toxo may pass it to their newborn child. The toxo antibody test shows whether you have been exposed to toxo. A positive test does not mean that you have toxo encephalitis. However, a negative antibody test means that you are not infected with toxo. Brain scans by computerized tomography (CT scan) or magnetic resonance imaging (MRI scan) are also used to diagnose toxo. A CT scan for toxo can look very similar to scans for other opportunistic infections. An MRI scan is more sensitive and can make it easier to diagnose toxo.

HOW IS TOXO TREATED? Toxo is treated with a combination of pyrimethamine (Daraprim) and sulfadiazine. Both drugs can cross the blood-brain barrier. The toxoplasma gondii parasites need vitamin B to live. Pyrimethamine stops toxo from getting vitamin B. Sulfadiazine prevents toxo from using it. The normal dosage of these drugs is 50 to 75mg of pyrimethamine with 2 to 4 grams per day of sulfadiazine. These drugs both interfere with vitamin B and can cause anemia. People with toxo usually take leucovorin, a form of folic acid (a B vitamin), to prevent anemia. This combination of drugs is very effective against toxo. Over 80% of people show improvement within 2 to 3 weeks. Toxo usually comes back after the first episode. People who have had toxo should keep taking the anti-toxo drugs at a lower, maintenance dose.

HOW DO I CHOOSE A TREATMENT FOR TOXO? If you are diagnosed with toxo, your health care provider will probably prescribe pyrimethamine and sulfadiazine. This combination can cause a drop in white blood cells, and kidney problems. Also, sulfadiazine is a sulfa drug. Almost half the people who take it have an allergic reaction. This usually is a skin rash, and sometimes a fever.

Allergic reactions can be overcome using a desensitization procedure. Patients start with a very small amount of the drug. They get increasing amounts until they can tolerate the full dose. People who cannot tolerate sulfa drugs can use clindamycin (Cleocin) instead of sulfadiazine in the combination.

CAN TOXO BE PREVENTED? The best way to prevent toxo is to take strong antiretroviral medications (ARVs). You can be tested to see if you have been exposed to toxo. If not, you can reduce your risk of infection by not eating undercooked meat or fish, and by wearing gloves and a face mask and washing thoroughly if you clean a cat box. If you have less than 100 CD4 cells, you should take medication to prevent toxo. People with less than 200 CD4 cells usually take Bactrim or Septra (see Fact Sheet 535) to prevent pneumocystis pneumonia (PCP). These drugs also protect you against toxo. See Fact Sheet 515 for more information on PCP. If you cant tolerate Bactrim, your health care provider can use other drugs.

THE BOTTOM LINE Toxoplasmosis is a serious opportunistic infection. If you have not been exposed, you can reduce your risk of exposure by not eating undercooked meat or fish, and taking extra precautions if you clean a cat box. You can take strong ARVs to keep your CD4 cell count up. This should prevent toxoplasmosis from causing health problems. If your CD4 cell count falls below 100, talk with your health care provider about taking drugs to prevent toxo. If you develop headaches, disorientation, seizures, or other possible signs of toxo, see your health care provider immediately. With early diagnosis and treatment, toxo can be treated effectively. If you do develop toxo, you should continue to take the anti-toxo drugs to prevent another episode.

WHAT IS TB? Tuberculosis (TB) is an infection caused by bacteria. TB usually affects the lungs, but sometimes can affect other organs, especially for people with HIV and a CD4 cell count under 200. TB is a very serious disease worldwide. Almost one-third of the world's population, and one third of people with HIV are infected with TB. A healthy immune system can usually prevent active disease. TB is a major cause of death for people with HIV worldwide, according to the World Health Organization. The name tuberculosis comes from tubercles. These are small, hard lumps that form when the immune system builds a wall around the TB bacteria in the lungs. TB in the lungs is called pulmonary TB. The infection can spread from the lungs to the kidneys, spine and brain. This is called extrapulmonary TB. It only shows up in people who have already been infected with TB but who have not been treated. People with HIV who live in areas where TB is common might develop extrapulmonary TB. Active TB in the lungs can cause coughing for more than 3 weeks, weight loss, constant fatigue, night sweats, and fevers, especially in the evening. These are like the symptoms caused by Pneumocystis pneumonia (PCP, see fact sheet 515). The symptoms can vary if TB is in other parts of the body. If people with HIV and TB have unexplained symptoms, they should rule out active TB disease. TB is transmitted through the air, when someone with active TB of the lung coughs, sneezes, or talks. The ultraviolet rays in sunlight can kill TB. Good ventilation reduces the risk of TB infection. However, people who live in close contact with people who have active TB become infected easily. This is especially true if you have advanced HIV disease. You can become infected with TB at any CD4 level.

TB AND HIV: A BAD PAIR Many viruses and bacteria live in our bodies. A healthy immune system will control these germs so they won't make us sick. If HIV weakens our immune system, they can cause opportunistic infections.

The rate of TB for people with HIV in the United States is 40 times the rate for people who aren't HIV-infected. TB rates all over the world are increasing because of HIV disease. TB can make HIV multiply faster, lower the CD4 cell count, and make HIV disease worse. This makes it important for people with HIV to prevent and treat TB.

HOW IS TB DIAGNOSED? There is a simple skin test for TB infection. A protein found in TB bacteria is injected into the skin of your arm. If your skin reacts with swelling more than a certain size, you have probably been infected with the TB bacteria. People with HIV should get a TB skin test to find out if they were exposed to TB in the past. If HIV or another disease has damaged your immune system, you might not show any reaction to the skin test, even if you're infected. This condition is called "anergy". If you have anergy, the most common way to test for TB is a sputum culture (see next paragraph.) A positive skin test usually doesn't mean you have active TB. Your health care provider will check x-rays of your lungs, ask you about other symptoms, examine samples of your sputum (fluid produced in the airways and lungs) and try to grow TB bacteria from those samples. They might also try to grow TB from samples taken from other parts of your body where TB can show up. This can take from two to four weeks depending on what method is used. It is difficult to diagnose active TB, especially in people with HIV, because it can look like pneumonia, other lung problems, or other infections. It can show up outside of the lungs. However, newer, faster tests are being developed.

HOW IS TB TREATED? If you are infected with TB, but don't have the active disease, you should be treated with an antibiotic called isoniazid (INH) for at least 6 months, or with INH plus one or two other drugs for 3 months. INH can cause liver problems, especially for black or Hispanic women. In 2011 a large study showed that using a once a week dose of INH with rifapentine for 3 months was equally effective. The US Centers for Disase Control now recommends this shorter course of treatment. Unfortunately, rifapentine interacts with some protease inhibitors. Dosage adjustments may be required but have not yet been studied. If you have active TB disease, you will be treated with antibiotics. Because the TB bacteria can develop resistance to individual drugs, you will be given a combination of antibiotics. TB drugs

must be taken for at least 6 months. but most cases of TB can be cured with existing antibiotics. If you don't keep taking the medications, the TB in your body might become resistant and the anti-TB drugs will stop working. There are types of TB that are resistant to some antibiotics. These are called multi-drug resistant TB (MDR-TB) or extensively drug resistant TB (XDR-TB). These types of TB are much harder to treat. More medications have to be taken for a longer period of time. Cure rates are lower than for regular TB. Sirturo (bedaquiline) is the first new TB drug in over 40 years. The FDA approved it at the end of 2012. It works against TB with resistance to current drugs.

MEDICATION PROBLEMS Some of the antibiotics used to treat TB can damage your liver or kidneys; so can some antiretroviral medication (ARVs. see fact sheet 403.) It can be difficult to take drugs for both TB and HIV at the same time. INH can cause peripheral neuropathy (see Fact Sheet 555), as can several ARVs, so there can be problems if these drugs are taken together. TB treatment can cause "immune restoration syndrome." (see fact sheet 483. Also, many ARVs interact with rifampin or rifabutin, which are commonly used to fight TB. They can drop the levels of ARVs in your blood too low to control HIV. ARVs can raise the levels of these TB drugs high enough to cause serious side effects. Rifampin should not be used with most protease inhibitors or non-nucleoside reverse transcriptase inhibitors. Rifabutin can be used in some cases, but drug doses might have to be changed. There are special guidelines if you take drugs to fight TB and HIV at the same time. They are available on the Internet at http://www.cdc.gov/tb/publications/factsheets/treatment/treatmentHIVpositive.htm. Also, people with a CD4 cell count below 100 should take rifabutin at least 3 times a week. This reduces the risk of their TB becoming resistant to rifabutin. For these reasons, TB should usually be cured first before ART is started. However, this may not be possible if CD4 cell counts are low.

THE BOTTOM LINE TB is a very serious disease worldwide and kills more people with HIV than any other disease. TB and HIV both make each other worse.

There are effective treatments for TB infection, and for active TB disease. If you are exposed to TB, or have signs of TB, get tested and treated. The treatments for TB take a long time, and can be difficult to take at the same time as ARVs, but they can cure TB. Some TB drugs interact with ARVs, so treatment has to be carefully planned if you have both HIV and TB. Be sure you understand how important it is to take TB medications for the complete length of time they are prescribed.

WHAT IS AIDS WASTING? AIDS wasting is the involuntary loss of more than 10% of body weight, plus more than 30 days of either diarrhea, or weakness and fever. Wasting is linked to disease progression and death. Losing just 5% of body weight can have the same negative effects.Although the incidence of wasting syndrome has decreased dramatically since 1996, wasting is still a problem for people with AIDS, even people whose HIV is controlled by medications. Part of the weight lost during wasting is fat. More important is the loss of muscle mass. This is also called lean body mass, or body cell mass. Lean body mass can be measured by bioelectrical impedance analysis (BIA) or by a full body x-ray (DEXA) scan. These are simple, painless office procedures. AIDS wasting and lipoatrophy can both cause some body shape changes. See Fact Sheet 553 for more information on lipodystrophy. Wasting is the loss of weight and muscle. Lipoatrophy can cause a loss of fat under the skin. Wasting is not the same as fat loss caused by lipodystrophy. However, wasting in women can start with a loss of fat.

WHAT CAUSES AIDS WASTING? Several factors contribute to AIDS wasting:

Low food intake: Low appetite is common with HIV. Also, some AIDS drugs have to be taken with an empty stomach, or with a meal. It can be difficult for some people with AIDS to eat when theyre hungry. Drug side effects such as nausea, changes in the sense of taste, or tingling around the mouth also decrease appetite. Opportunistic infections in the mouth or throat can make it painful to eat. Infections in the gut can make people feel full after eating just a little food. Depression can also lower appetite. Finally, lack of money or energy may make it difficult to shop for food or prepare meals.

Poor nutrient absorption: Healthy people absorb nutrients through the small intestine. In HIV disease, several infections (including parasites) can interfere with this process. HIV may directly affect the intestinal lining and reduce nutrient absorption. Diarrhea causes loss of calories and nutrients. Altered metabolism: Food processing and protein building are affected by HIV disease. Even before any symptoms show up, you need more energy. This might be caused by the increased activity of the immune system. People with HIV need more calories just to maintain their body weight.

Hormone levels can affect the metabolism. HIV seems to change some hormone levels including testosterone and thyroid. Also, cytokines play a role in wasting. Cytokines are proteins that produce inflammation to help the body fight infections. People with HIV have very high levels of cytokines. This makes the body produce more fats and sugars, but less protein. Unfortunately, these factors can work together to create a downward spiral. For example, infections may increase the bodys energy requirements. At the same time, they can interfere with nutrient absorption and cause fatigue. This can reduce appetite and make people less able to shop for or cook their meals. They eat less, which accelerates the process.

HOW IS WASTING TREATED? There is no standard treatment for AIDS Wasting. However, successful antiretroviral treatment usually leads to healthy weight gain. Treatments for wasting deal with each of the causes mentioned above. .Decreasing viral load to undetectable levels usually leads to increased weight (average 10-25% increase in a year).

Reducing nausea and vomiting helps increase food intake. Also, appetite stimulants including Megace and Marinol have been used. Megace, unfortunately, is associated with increases in body fat, blood clots, bone problems, and diabetes. Marinol (dronabinol) is sometimes used to increase appetite. It is a synthetic form of a substance found in marijuana. Medications that fight nausea can also help. AIDS activists have long urged the legalization of marijuana. It reduces nausea and stimulates the appetite. From the late 1990s to the present, 15 states and the District of Columbia legalized the medical use of marijuana. See Fact Sheet 731 for more information on marijuana. Treating diarrhea and opportunistic infections in the intestines helps alleviate poor nutrient absorption. There has been a lot of progress in this area. However, two parasitic infections cryptosporidiosis and microsporidiosis are still extremely difficult to treat.Another approach is the use of nutritional supplements like Ensure and Advera. These have been specifically designed to provide easy-to-absorb nutrients. However, they have not been carefully studied and contain a lot of sugar. Nutritional supplements like

Juven or whey protein may also help increase weight. However, some people are allergic to whey. Consult with your health care provider before using nutritional supplements. Supplements should be used in addition to a balanced diet. Treating changes in metabolism: Hormone treatments are being examined. Human growth hormone (Serostim) increases weight and lean body mass, while decreasing fat mass. However, it is extremely expensive, can cause serious side effects, and can cost over $40,000 per year. Some nutritional experts believe it can be effective at doses lower than the FDA-approved dose. Testosterone and anabolic (muscle building) agents like oxandrolone or nandrolone might also help treat wasting. They have being studied alone and in combination with exercise.

Testosterone and anabolic (muscle building) agents like oxandrolone or nandrolone might also help treat wasting. They have been studied in HIV by themselves and in combination with exercise. Progressive resistance training (PRT) is a form of exercise using weights and machines. A recent study found that PRT gave results like oxandrolone (an anabolic steroid) in increasing lean body mass. PRT was also more effective than oxandrolone in increasing physical functioning. It is also less expensive. Exercise can also improve mood and cholesterol, and can strengthen bone. See fact sheet 802 for more information on exercise and HIV.

THE BOTTOM LINE AIDS wasting is not well understood. However, it is clear that people with HIV disease need to avoid the loss of lean body mass. Various treatments for wasting are being studied. Be sure to monitor your weight. Maintain your intake of nutritious foods even if your appetite is low. Get treatment right away for serious diarrhea or any infection of your digestive system. These might cause problems with the absorption of nutrients.

WHICH CANCERS AFFECT PEOPLE WITH HIV?

Cancer is the uncontrolled growth of abnormal cells in the body. Cancer cells are called malignant cells. Malignant means bad and getting worse.Cancer is the uncontrolled growth of abnormal cells in the body. Cancer cells are called malignant cells. Malignant means bad and getting worse. Cancer has been associated with AIDS from the beginning of the epidemic. A group of unusual cases of Kaposis sarcoma (KS) which normally shows up in older men was identified in young men in Los Angeles. See fact sheet 511 for more information on KS.

Many types of cancer occur in people with HIV. Some cancers, called AIDS-defining cancers, are part of the official definition of AIDS. They include KS, Non-Hodgkins Lymphoma (see fact sheet 512), and severe cervical cancer. The official Centers for Disease Control definition of AIDS includes people who test positive for HIV and who have one of the following cancers: invasive cervical cancer (see fact sheet 510), non-Hodgkin lymphoma, or KS. With the use of antiretroviral therapy, the rates of these AIDS-related cancers have dropped significantly. At the same time, people with HIV are at higher than average risk for several other cancers, including Hodgkin lymphoma and cancers of the anus, lung, liver, and skin, The number of cases of these other cancers is increasing in people with HIV.

DOES HIV INCREASE THE RISK OF CANCER?

Several studies found higher rates of some cancers in people with HIV, compared to the general population. Many factors could explain this: People with HIV are living longer. Older age is linked to higher rates of cancer. People with HIV have a high rate of smoking, which contributes to several types of cancer HIV infection weakens the immune system. This might allow some cancer cells to multiply. HIV also causes ongoing activation of the Immune system. This may increase some cancers. Some cancers (such as KS and non-Hodgkins lymphoma) appear to be linked to the lowest (nadir) CD4 count a person had. Several cancers are linked to viral infections. These are shown in the following table. CANCERS Kaposi's Sarcoma (see fact sheet 508) Non-Hodgkin's Lymphoma (fact sheet 512) Cervical and anal cancers (fact sheet 510) Hodgkin's Disease Skin cancers (some) Liver cancer VIRUSES Human herpes virus 8 Human herpes virus 8, Epstein-Barr virus Human papilloma virus (HPV) Epstein-Barr Virus Human papilloma virus Hepatitis B, Hepatitis C

People with HIV have higher rates of these infections than the general population.

IS CANCER A SIGN OF ACCELERATED AGING IN PEOPLE WITH HIV?

Some cancers appear in people with HIV at a younger age than in the general population. Some people think that HIV accelerates aging, and that cancers are one sign of this..A careful study suggested that this is not true for most cancers. The study found that most people with HIV are studied at younger ages than the general population. Most people with HIV are between ages 30 and 55, so cancers seem to occur at younger ages. For the general population, increasing age is linked to higher rates of cancer. As the AIDS population ages, the age of cancer cases will increase. However, people with HIV do appear to develop anal cancer, lung cancer, and Hodgkin lymphoma at a younger age. This may be due to the effects of HIV on these cancers. It could also be caused by early exposure to risk factors for these types of cancer, such as earlier age of starting smoking or sexual activity (leading to HPV infection). Also, people with HIV are monitored more carefully from a younger age, so cancers may be detected earlier.

HOW CAN PEOPLE WITH HIV REDUCE THEIR RISK OF CANCER?

1. Stop smoking. Smoking is linked to lung cancer, but also to head and neck cancers, kidney and colon cancer. It may also increase the risk of cervical cancer. 2. Reduce consumption of alcohol, which can contribute to liver cancer. 3. If appropriate, get vaccinated against human papillomavirus (HPV), and hepatitis A & B. 4. Get tested for hepatitis B and C, which increase the risk of liver cancer. If you are infected, be sure your health care provider monitors these infections. 5. Get annual cervical and anal Papanicolaou (PAP) tests. Anal testing should be done for both men and women. However, it is not generally available. Talk to your health care provider, 6. Follow standard guidelines for breast, colon, and prostate exams. 7. Use sunscreen and avoid overexposure to the sun.