WHAT ARE TREATMENT INTERRUPTIONS? WHAT ARE THE RISKS? THE BOTTOM LINE WHAT ARE TREATMENT INTERRUPTIONS? Researchers have studied interruptions of antiretroviral therapy (ART) for various reasons. These treatment interruptions are usually called structured or strategic treatment interruptions (STIs), or structured intermittent therapy (SIT). During most treatment breaks, the viral load climbs very quickly and CD4 cell counts drop. Some people get the same symptoms as if they were newly infected with HIV. Fact Sheet 103 has more information on acute HIV infection. When people start medications again after taking a break, they might experience more side effects, like when they first started taking antiretroviral drugs (ARVs). They might also have difficulty with adherence (see fact sheet 405), taking all of their doses correctly. There were several reasons why treatment interruptions were studied: 1. People who started treatment as soon as they got infected. It seemed possible that if ARVs were started immediately after HIV infection, they could protect the immune system from damage. The hope was that in these rare cases, patients could stop taking medications. Unfortunately, this approach now does not seem to work. There are several reasons. First, most people aren’t aware that they have just been infected with HIV. Once HIV infection has continued for a few months, it’s too late for this approach. Also, researchers cannot predict which patients might be able to stop their therapy. But most important, newer research shows that the immune response in these patients does not continue to protect them against HIV disease. 2. People on therapy who don’t meet current treatment guidelines. During the past few years, HIV treatment guidelines have gotten more conservative. They recommend that people start treatment with lower CD4 cell counts than previous guidelines. See Fact Sheet 404 for more information on treatment guidelines for HIV. Some people started treatment with higher CD4 cell counts than today’s guidelines. In some cases, their doctors will recommend that they stop taking medications. They check their CD4 cell counts and their viral loads regularly. They go back on therapy when they meet the current guidelines. As more doctors follow the newer guidelines and delay treatment for their patients, there won’t be as many people who started treatment "too early." 3. Using "intermittent therapy" to reduce side effects and costs. Doctors have studied "cycling" people on and off of ART. Their goal was to give patients more time off of therapy, and reduce side effects, while still controlling HIV. Two major clinical studies of this type of treatment interruption were stopped. There were more cases of AIDS diseease progression and death among people who stopped treatment. Two types of "cycling" were studied. The first type put patients on a fixed schedule. They would start and stop therapy for a certain number of days or weeks. The second type of cycling uses CD4 cell counts and/or viral loads to decide when to end a treatment break and start medications again. Neither of these approaches seems to work. 4. Stopping treatment to deal with drug side effects. Some patients get very serious side effects. In some cases they can switch medications. However, if they have already used most antiretroviral drugs (ARVs), they might need to take a break from treatment to recover from the side effects before getting back on treatment. 5. Waiting for a new drug to be approved. Some doctors used to stop treatment for their patients when there wasn’t any treatment regimen that could control their virus. Maybe HIV had developed resistance to all of the available ARVs. Fact Sheet 126 has more information on resistance. During a treatment interruption, the "wild type" virus becomes more common. At first, researchers thought this was a good thing, because the wild type virus can be controlled by medications. However, most viral resistance doesn’t go away. It can come back quickly when drugs are re-started. Most patients do better if they keep taking medications, even if HIV is not totally controlled. Do not stop your ART without careful discussion with your doctor. Viral load and CD4 cell levels should be carefully monitored. Do not stop taking medications to prevent or treat opportunistic infections (see fact sheet 500) should not be interrupted. WHAT ARE THE RISKS? The biggest risks of an STI are that the viral load will climb and the CD4 cell count will drop. These risks are greatest for people whose virus is not under control or who have a low CD4 cell count. If you have only 50 CD4 cells, losing another 10 might have serious consequences. Stopping medications to prevent opportunistic infections can allow them to develop. People who stopped treatment have a much higher chance of developing an opportunistic infection. Stopping and re-starting medications could make it easier for the virus to develop resistance to medications. This has happened to some patients in STI studies. People ending a treatment interruption might have a hard time re-starting medications. This can be due to side effects, or due to psychological difficulties in getting back on treatment. THE BOTTOM LINE HIV patients stop ART for various reasons. If we can learn how to use treatment interruptions safely, patients might be able to take periods of time off of ARVs. This could mean fewer side effects and lower drug costs. However, we will have to learn how to avoid HIV disease progression, and minimize drug resistance and transmission of HIV. So far, large research studies have not shown any benefits to discontinuing therapy. source: The AIDS Infonet

The full text of these guidelines is available on the Internet. WHY DO THE GUIDELINES KEEP CHANGING? VIRAL LOAD AND CD4 CELL TESTING RESISTANCE TESTING WHEN TO START TREATMENT GOALS OF THERAPY WHAT DRUGS SHOULD BE USED FIRST? INTERRUPTING TREATMENT WHEN TO CHANGE WHAT TO CHANGE TO? WHY DO THE GUIDELINES KEEP CHANGING? We keep learning more about the best way to fight HIV. In 1998, the US Department of Health and Human Services created a panel of physicians, researchers, and consumers to develop treatment guidelines. They constantly review AIDS research results. The guidelines are updated about once each year. The panel released the latest guidelines in October 2006. NOTE: These are guidelines, not rules. Patients should receive individualized care from a health care provider with experience treating HIV infection. The full text of these guidelines is available on the Internet at https://www.aidsinfo.nih.gov/guidelines VIRAL LOAD AND CD4 CELL TESTING Viral load and CD4 cell tests provide critical information for decisions on antiretroviral therapy (ART). Before changing treatment, the tests should be repeated to confirm the results. Fact Sheet 124 has more information on CD4 cell tests and Fact Sheet 125 covers viral load testing. Viral load should be tested: Before starting or changing medications. This provides a reference value; About 2 to 8 weeks after starting or changing medications. This shows whether the new drugs are working; Every 3 or 4 months. This helps make sure the medications are still working. For patients who haven’t started taking medications, it helps decide when to start. CD4 cell counts should be done: When someone first tests HIV-positive Every 3 to 6 months to monitor the strength of the immune system RESISTANCE TESTING Viral resistance testing helps health care providers choose the most effective drugs. See Fact Sheet 126 for more information. Resistance testing is recommended when viral load is not controlled by new medications, or when it “breaks through” a regimen that used to work. The guidelines recommend resistance testing before starting antiretroviral treatment (ART). It can also make sense for people who don’t need to start ART yet. This can show if the person got infected with drug-resistant virus. WHEN TO START TREATMENT Patients with symptoms of HIV disease or with less than 200 CD4 cells should all be treated. Patients with no symptoms who have less than 350 CD4 cells OR viral load over 100,000 should be offered treatment. Consider the risk of disease progression and the patient’s willingness to start therapy. Some experts would delay treatment for patients with 200 to 350 CD4 cells and viral loads under 100,000. Patients with no symptoms, more than 350 CD4 cells AND a viral load below 100,000 do not need to start treatment. They should get regular viral load and CD4 tests. However, some experts would treat these patients. GOALS OF THERAPY The guidelines list the following goals for HIV therapy: Reduce viral load as much as possible for as long as possible Restore or preserve the immune system Improve the patient’s quality of life Reduce sickness and death due to HIV The following tools are suggested to help achieve these goals: Maximize adherence. Help the patient take medications correctly. Think about future regimens when choosing drugs. Keep future options open Use resistance testing when it will help. WHAT DRUGS SHOULD BE USED FIRST? The guidelines list several preferred regimens for people starting anti-HIV treatment. They include efavirenz (Sustiva) or atazanavir (Reyataz), or lopinavir (Kaletra), each boosted with ritonavir, plus Truvada or Combivir (each of which contains two nucleoside analog drugs in a single pill). Many other combinations are listed as “alternative regimens.” They include nevirapine (Viramune), Kaletra, fosamprenavir boosted or unboosted, or atazanavir unboosted, together with Truvada, Combivir, or Epzicom (abacavir plus lamivudine in a single pill). Other combinations are listed for use only when a preferred or alternative NNRTI- or PI-containing regiment cannot or should not be used. Several drugs or combinations are listed as “Not Recommended.” Some are not recommended for initial therapy due to low anti-HIV activity or inconvenience. Others are not recommended at any time. These include any nuke or non-nuke by itself (monotherapy) or just two nukes because these treatments generally have only limited benefits for a short period of time. Also, the guidelines recommend not using the triple-nuke regimens except for Trizivir (abacavir + zidovudine + lamivudine) or possibly tenofovir + Combivir (zidovudine + lamivudine). There are special considerations for the treatment of pregnant women (Fact Sheet 611), adolescents, drug users, people also infected with hepatitis B (Fact Sheet 506) or hepatitis C(Fact Sheet 506) or with tuberculosis (Fact Sheet 518). INTERRUPTING TREATMENT A patient may need to interrupt treatment for several reasons: side effects are intolerable there’s a drug interaction if they run out of any of their medications or if they have surgery scheduled women might choose to stop treatment during the first 3 months of pregnancy. Treatment interruptions are not recommended in response to treatment failure. ART should only be stopped if your health care provider recommends it. Two large studies showed that people who interrupted treatment had a higher rate of HIV-related health problems or death. For more information, see Fact Sheet 406 on treatment interruptions. WHEN TO CHANGE Treatment should be changed due to treatment failure, or intolerance of current drugs. Treatment failure: Within 6 months after starting a treatment, the viral load should drop below 400 copies. Within 1 year, it should be less than 50 copies. If the viral load does not drop this much, change the treatment. Other signs of treatment failure include: An increase in viral load from undetectable to detectable levels; Failure to increase CD4 cells by 25 to 50 during the first year; or A new AIDS-related illness. Intolerance: If a patient cannot take the prescribed drugs because of their side effects or interactions with other needed medications, the drugs should be changed. WHAT TO CHANGE TO? Decisions to change ART should include a review of prior treatments, physical exam, resistance testing, adherence

Coming soon.

WHAT IS RESISTANCE? HOW DOES RESISTANCE DEVELOP? TYPES OF RESISTANCE PHENOTYPIC TESTING GENOTYPIC TESTING VIRTUAL PHENOTYPE CROSS RESISTANCE PROBLEMS WITH RESISTANCE TESTING WHAT IS RESISTANCE? HIV is "resistant" to a drug if it keeps multiplying rapidly while you are taking the drug. Changes (mutations) in the virus cause resistance. HIV mutates almost every time a new copy is made. Not every mutation causes resistance. The "wild type" virus is the most common form of HIV. Anything different from the wild type is considered a mutation. An antiretroviral drug (ARV) won?t control a virus that is resistant to it. It can "escape" from the drug. If you keep taking the drug, the resistant virus will multiply the fastest. This is called "selective pressure." If you stop taking medications, there is no selective pressure. The wild type virus will multiply the fastest. Although tests may not detect any drug resistance, it might come back if you re-start the same drugs. Resistance testing helps health care providers make better treatment decisions for their patients. HOW DOES RESISTANCE DEVELOP? HIV usually becomes resistant when it is not totally controlled by drugs someone is taking. However, more people are getting infected with HIV that is already resistant to one or more ARVs. The more that HIV multiplies, the more mutations show up. These mutations happen by accident. The virus doesn’t "figure out" which mutations will resist medications. Just one mutation can make HIV resistant to some drugs. This is true for 3TC (Epivir) and the non-nucleoside reverse transcriptase inhibitors (NNRTIs). However, HIV has to go through a series of mutations to develop resistance to other drugs, including most protease inhibitors. The best way to prevent resistance is to control HIV by taking strong ARVs. If you miss doses of your medications, HIV will multiply more easily. More mutations will occur. Some of them could cause resistance. If you have to stop taking any ARV, talk to your health care provider. You may have to stop some drugs sooner than others. If you stop taking drugs while the virus is under control, you should be able to use them again. TYPES OF RESISTANCE There are three types of resistance: Clinical resistance: HIV multiplies rapidly in your body even though you’re taking ARVs. Phenotypic resistance: HIV multiplies in a test tube when ARVs are added. Genotypic resistance: The genetic code of HIV has mutations that are linked to drug resistance. Clinical resistance shows up as a higher viral load, lower CD4 count, or opportunistic infections (see Fact Sheet 500). Laboratory tests can measure phenotypic and genotypic resistance. PHENOTYPIC TESTING A sample of HIV is grown in the laboratory. A dose of one ARV is added. The growth rate of the HIV is compared to the rate of wild type virus. If the sample grows more than normal, it is resistant to the medication. Phenotypic resistance is reported as "fold" resistance. If the test sample grows twenty times as much as normal, it has "20-fold resistance". Phenotypic tests cost about $800. It used to take over a month to get the results. New phenotypic tests are somewhat quicker. GENOTYPIC TESTING The genetic code of the sample virus is compared to the wild type. The code is a long chain of molecules called nucleotides. Each group of three nucleotides, called a "codon", defines a particular amino acid used to build a new virus. Mutations are described by a combination of letters and numbers, for example K103N. The first letter (K) is the code for the amino acid in the wild type virus. The number (103) identifies the position of the codon. The second letter (N) is the code for the "changed" amino acid in the mutant sample. Genotypic testing costs about $250. Results come back in about two weeks. VIRTUAL PHENOTYPE This test is really a method of interpreting genotypic test results. First, genotypic testing is done on the sample. Phenotypic test results for other virus samples with a similar genotypic pattern are taken from a database. These matched samples tell you how the virus is likely to behave. The virtual phenotype is faster and less expensive than a phenotypic test. CROSS-RESISTANCE Sometimes a mutant version of HIV is resistant to more than one drug. When this happens, the drugs are called "cross-resistant". For example, most HIV that is resistant to nevirapine (Viramune) is also resistant to efavirenz (Sustiva). This means that nevirapine and efavirenz are cross-resistant. Cross-resistance is important when you change medications. You need to choose new drugs that are not cross-resistant to drugs you’ve already taken. We do not totally understand cross-resistance. However, many drugs are at least partly cross-resistant. As HIV develops more mutations, it gets harder to control. Take every dose of your ARVs according to instructions. This reduces the risk of resistance and cross-resistance. It saves the most options for changing medications in the future. PROBLEMS WITH RESISTANCE TESTING Resistance tests are not available everywhere. They are expensive. However, they are becoming more common, faster and cheaper. The tests aren’t good at detecting "minority" mutations (less than 20% of the virus population.) Also, they work better when the viral load is higher. If your viral load is very low, the tests might not work. Tests usually cannot be run if the patient’s viral load is less than 500 to 1,000 copies per ml. Test results can be difficult to understand. Drugs that should work according to the tests sometimes don’t work, and vice versa. Sometimes genotypic and phenotypic tests give conflicting results for the same patient. Some mutations can "reverse" or reduce resistance to some medications. Recent research suggests that a genotypic resistance test should be done for every patient before they start taking ARVs. This saves money by avoiding putting someone on ARVs that will not work for them. source: The AIDS Infonet

WHAT IS ART? WHAT IS THE HIV LIFE CYCLE? APPROVED ARV DRUGS HOW ARE THE DRUGS USED? CAN THESE DRUGS CURE AIDS? WHEN DO I START? WHICH DRUGS DO I USE? WHAT’S NEXT? WHAT IS ARV THERAPY? ARV therapy means treating viral infections like HIV with drugs. The drugs do not kill the virus. However, they slow down the growth of the virus. When the virus is slowed down, so is HIV disease. Antiretroviral drugs are referred to as ARV. ARV therapy is referred to as ART. WHAT IS THE HIV LIFE CYCLE? There are several steps in the HIV life cycle. See Fact Sheet 400 for a diagram. Free virus circulates in the bloodstream. HIV attaches to a cell. HIV empties its contents into the cell (infects the cell). The HIV genetic code (RNA) is changed into DNA by the reverse transcriptase enzyme. The HIV DNA is built into the infected cell’s DNA by the integrase enzyme. When the infected cell reproduces, it activates the HIV DNA, which makes the raw material for new HIV viruses. Packets of material for a new virus come together. The immature virus pushes out of the infected cell in a process called "budding." The immature virus breaks free of the infected cell. The new virus matures: raw materials are cut by the protease enzyme and assembled into a functioning virus. APPROVED ARV DRUGS Each type, or "class", of ARV drugs attacks HIV in a different way. The first class of anti-HIV drugs was the nucleoside reverse transcriptase inhibitors, also called "nukes". These drugs work by blocking Step 4, where the HIV genetic material is converted from RNA into DNA. Drugs in use in this class include: AZT (ZDV, zidovudine, Retrovir®) ddI (didanosine, Videx®) d4T (stavudine, Zerit®) 3TC (lamivudine, Epivir®) Abacavir (Ziagen®) Tenofovir (Viread®) Combivir® (AZT/3TC combination) Trizivir® (AZT/3TC/Abacavir combination) Emtricitabine (FTC, Emtriva®) Epzicom? (3TC/abacavir combination) Truvada? (tenofovir/emtricitabine combination) Another class of drugs blocks the same step of the life cycle, but in a different way. This class is the non-nucleoside reverse transcriptase inhibitors, or NNRTIs. Three NNRTIs have been approved: Nevirapine (NVP, Viramune®) Delavirdine (DLV, Rescriptor®) Efavirenz (EFV, Sustiva®) The third class of antiviral drugs block Step 10, where the raw material for new HIV virus is cut into specific pieces. Ten protease inhibitors are being used: Saquinavir (SQV, Invirase®) Indinavir (IDV, Crixivan®) Ritonavir (RTV, Norvir®) Nelfinavir (NFV, Viracept®) Amprenavir (APV, Agenerase®) Lopinavir (LPV, Kaletra®) Atazanavir (TAZ, Reyataz®) Fosamprenavir (908, Lexiva®) Tipranavir (PNU140690, Aptivus®) Darunavir (TMC114, Prezista®) The newest class of ARV drugs includes fusion inhibitors. They prevent HIV from attaching to a cell by blocking Step 2 of the life cycle. One fusion inhibitor has been approved: Enfuvirtide (T-20, Fuzeon®) HOW ARE THE DRUGS USED? When HIV multiplies, most of the new copies are mutations: they are slightly different from the original virus. Some mutations keep multiplying even when you are taking an ARV drug. When this happens, the drug will stop working. This is called "developing resistance" to the drug. If only one ARV drug is used, it is easy for the virus to develop resistance. But if two drugs are used, a successful mutant would have to "get around" both drugs at the same time. And if three drugs are used, especially if they attack HIV at different points in its life cycle, it’s very hard for a mutation to show up that can resist all three drugs at the same time. Using a triple-drug combination means that it takes much longer for resistance to develop. For this reason, using just one ARV drug (monotherapy) is not recommended. CAN THESE DRUGS CURE AIDS? A blood test called the "viral load" measures the amount of HIV virus in your bloodstream. People with lower viral loads stay healthier longer. See Fact Sheet 125 for more information on the viral load test. Some people’s viral load is so low that it is "undetectable" by the viral load test. This does not mean that all the virus is gone. Researchers used to believe that ARV therapy could eventually kill off all of the HIV virus in the body. Now this seems unlikely. The drugs do not "cure" AIDS. However, they make it possible for people with AIDS to live a long time. WHEN DO I START? There is not a clear answer to this question. Most doctors will consider three things: 1) your viral load; 2) your CD4 cell count; and 3) any symptoms you’ve had. ART is usually started if your viral load is over 100,000, if your CD4 cell count is below 350, or if you?ve had any symptoms of HIV disease. See fact sheet 404 for more information on treatment guidelines. This is an important decision you should discuss with your doctor. WHICH DRUGS DO I USE? Each ARV drug has side effects. Some are serious. Refer to the fact sheet for each individual drug. Some combinations of drugs are easier to tolerate than others, and some seem to work better than others. Each person is different, and you and your doctor will have to decide which drugs to use. The viral load test is now being used to see if ARV drugs are working. If the viral load does not go down, or if it goes down but comes back up, it might be time to change ARV drugs. WHAT’S NEXT? New drugs are being developed in all four of the existing classes. Researchers are also trying to develop new types of drugs, such as drugs that will block other steps in the HIV life cycle, and drugs that will strengthen the body’s immune defenses. See fact sheets 460, 470 and 480 for more information on newer classes of drugs. source: The AIDS Infonet

WHAT IS DIDANOSINE? WHO SHOULD TAKE DIDANOSINE? WHAT ABOUT DRUG RESISTANCE? HOW IS DIDANOSINE TAKEN? WHAT ARE THE SIDE EFFECTS? HOW DOES DIDANOSINE REACT WITH OTHER DRUGS? WHAT IS DIDANOSINE? Didanosine (Videx®, ddI), is a drug used as part of antiretroviral therapy (ART). It is manufactured by Bristol-Myers Squibb and by Barr Laboratories. Didanosine is also known as ddI or dideoxyinosine. Didanosine is a nucleoside analog reverse transcriptase inhibitor, or nuke. These drugs block the reverse transcriptase enzyme. This enzyme changes HIV’s genetic material (RNA) into the form of DNA. This has to occur before HIV’s genetic code gets inserted into an infected cell’s own genetic codes. WHO SHOULD TAKE DIDANOSINE? Didanosine was approved in 1991 as an antiretroviral drug (ARV) for people with HIV infection. The generic version was approved in 2004. It has been studied in adults and children more than 2 weeks old. There are no absolute rules about when to start ART. You and your health care provider should consider your CD4 cell count, your viral load, any symptoms you are having, and your attitude about taking ART. Fact Sheet 404 has more information about guidelines for the use of ART. If you take didanosine with other ARVs, you can reduce your viral load to extremely low levels, and increase your CD4 cell counts. This should mean staying healthier longer. WHAT ABOUT DRUG RESISTANCE? Many new copies of HIV are mutations. They are slightly different from the original virus. Some mutations can keep multiplying even when you are taking an ARV. When this happens, the drug will stop working. This is called "developing resistance" to the drug. See Fact Sheet 126 for more information on resistance. Sometimes, if your virus develops resistance to one drug, it will also have resistance to other ARVs. This is called "cross-resistance." Resistance can develop quickly. It is very important to take ARVs according to instructions, on schedule, and not to skip or reduce doses. HOW IS DIDANOSINE TAKEN? Didanosine is available as a 200 mg chewable tablet (which can also be dissolved in water) and as a powder that is dissolved in water. Note: the 200 mg tablets became unavailable in October 2005. There is also an ?enteric coated? version of didanosine called Videx EC. It can be taken as a single capsule once a day. Videx EC does not contain a buffer, so side effects and drug interactions might be reduced. Videx EC should be taken with an empty stomach. Do not chew it; swallow it whole. The recommended dose of didanosine for adults is based on weight. For people weighing more than 132 pounds, the dose is 200mg (milligrams) in tablet form, or 250mg of powder, twice a day. For those weighing less than 132 pounds, the dose is 125mg in tablet form, or 167mg of powder, twice a day. Another formulation of didanosine can be taken just once a day. The dosage is two 200 mg tablets taken at the same time. However, the FDA said that twice-daily dosing of didanosine is preferred. Once-daily dosing should only be used by adults with a special need to take their medications just once a day. If you want to change how often you take didanosine, talk to your health care provider. If you have had liver or kidney problems, the dose of didanosine may need to be reduced. Didanosine cannot be absorbed in an acid environment. Didanosine contains a buffer to reduce the effects of stomach acid. Didanosine is taken on an empty stomach, 30 minutes before eating or two hours after a meal. Taking didanosine with food may reduce blood levels by as much as 50%. WHAT ARE THE SIDE EFFECTS? When you start any ART you may have temporary side effects such as headaches, high blood pressure, or a general sense of feeling ill. These side effects usually get better or disappear over time. The most common side effects of didanosine are diarrhea, headaches, vomiting and rash. Diarrhea, caused by the buffer in the tablets, is sometimes severe. Side effects are less common with the EC version of didanosine. The most serious side effects of didanosine are peripheral neuropathy, pancreatitis, and lactic acidosis: Peripheral neuropathy is a form of nerve damage. It occurs in up to 20% of people who take didanosine. It usually shows up as tingling, numbness, or a sharp burning sensation in the feet, legs, or hands. The nerve damage is usually temporary and will go away if you stop taking didanosine, or reduce the dose. If you continue to take didanosine after nerve damage shows up, it may become permanent. See Fact Sheet 555 for more information. Pancreatitis is an inflammation of the pancreas, a large gland located behind the stomach. Less than 7% of people get it, usually after taking didanosine for a few months. Pancreatitis can be fatal. If you are taking didanosine and have sharp pain near your stomach, back, or sides, with nausea and vomiting, stop taking didanosine immediately and call your health care provider. Pancreatitis is more common in older patients, people who have had it before, and those with kidney problems. Lactic acidosis is a buildup of lactic acid in the blood. This is a by-product of abnormal energy production by the cells. It may be caused by damage to the mitochondria. See Fact Sheet 556 for more information on mitochondrial toxicity. Lactic acidosis can cause severe damage to the pancreas and liver. Symptoms of lactic acidoss can include weight loss, abdominal pain, and severe fatigue. HOW DOES DIDANOSINE REACT WITH OTHER DRUGS? Didanosine can interact with other drugs or supplements you are taking. These interactions can change the amount of each drug in your bloodstream and cause an under- or overdose. New interactions are constantly being identified. Make sure that your health care provider knows about ALL drugs and supplements you are taking. Didanosine may be more effective if taken with hydroxyurea. However, this increases the risk of developing pancreatitis. Methadone decreases blood levels of

WHAT IS DIARRHEA? Diarrhea is an increase in the water content, frequency, and volume of bowel movements. It is frequent in people with HIV disease. Diarrhea can be a serious problem. Mild cases disappear within a few days. Severe cases can cause serious dehydration or nutritional problems. IS DIARRHEA DANGEROUS? The greatest risk of diarrhea is dehydration. You can lose up to a gallon of water each day. Along with the water, you lose minerals (electrolytes) that are important for normal body functions. The main electrolytes are sodium and potassium. Severe dehydration can cause the body to go into shock and is potentially fatal. Dehydration is more serious for infants and children than for adults. Anyone with diarrhea should drink plenty of clear liquids. Tea, chicken broth, ginger ale, or soda are good choices. These are better than plain water, which does not replace any electrolytes. Diarrhea that continues over a long period of time can cause poor absorption of nutrients. This can lead to wasting (see Fact Sheet 519). Diarrhea can be dangerous. Be sure your health care provider knows if your diarrhea lasts more than a few days. WHAT CAUSES DIARRHEA? It can be difficult to find out what is causing diarrhea. Diarrhea is sometimes caused by an infection in the stomach or intestines. It can also be caused by an inability to digest milk products (lactose intolderance), by problems with the pancreas, or by emotional stress. Bacteria, parasites, fungi, or viruses can cuase the infection. Parasites: The parasites cryptosporidium or microsporidium used to cause diarrhea in many people with HIV. The use of combination antiretroviral therapy has greatly reduced the rates of these problems. Antiretroviral medications: These can cause diarrhea. This is often true with nelfinavir (Viracept), ritonavir (Norvir), Kaletra, ddI (Videx), tipranavir (Aptivus), foscarnet (Foscavir), and interferon alfa (Roferon or Intron). Other causes: Taking antibiotics can kill off "good" bacteria in your gut and may cause diarrhea. Diarrhea can also be caused by an inability to digest milk products (lactose intolerance), by problems with the pancreas, or by emotional stress. HOW DO I KNOW WHAT IS CAUSING MY DIARRHEA? It can be difficult to find out what is causing diarrhea. Your health care provider will ask you what you have been eating and drinking recently, and whether you have been traveling. Samples of your bowel movement (or "stool") may be tested for signs of bacteria or parasites. Your health care provider may repeat this test if nothing shows up the first time. In some cases your blood or urine will also be tested. If these tests do not show the cause of diarrhea, your health care provider may look inside your digestive tract with a special tool or scope. The name of this procedure depends on where the health care provider is looking. "Endoscopy" is a general term that means "to look inside". A colonoscopy is a procedure where the health care provider examines the colon, and so on. The cause of about one third of all cases of diarrhea cannot be determined. HOW IS DIARRHEA TREATED? 1. CHANGE WHAT YOU EAT: Some foods can cause diarrhea, and others can help stop it. Don’t eat: dairy products (milk or cheeses) greasy or fried food fatty foods including butter, margarine, oils, or nuts spicy foods foods high in "insoluble" fiber. This includes raw fruits or vegetables, whole wheat bread, corn, or any fruit or vegetable skins or seeds. Do eat: bananas plain white rice applesauce cream of wheat or farina cereal toasted white bread or plain crackers plain macaroni or noodles boiled eggs oatmeal mashed potatoes yogurt (This is a dairy product, but it’s partially "digested" by the bacteria used to make it.) 2. DRUG TREATMENTS: Different medications are used to treat different types of diarrhea. Your health care provider will not be able to prescribe a medication without some idea of what is causing your diarrhea. You do not need a prescription for over-the-counter treatments. Some of these work very well for diarrhea, including: The amino acid L-glutamine Pepto-Bismol (Bismuth subsalicylate) Kaopectate (attapulgite) Imodium AD (loperamide) Some other products that are usually sold to treat constipation can also help with diarrhea. These products contain "soluble" fiber that adds bulk and absorbs water. This includes products like Metamucil, Citrucel, or other products that contain psyllium. 3. ALTERNATIVE THERAPIES FOR DIARRHEA Acidophilus capsules (which contain helpful bacteria) can help restore normal digestion, especially when you are taking antibiotics. Some types of yogurt contain "live cultures" of acidophilus that work the same way. Peppermint, ginger and nutmeg are believed to help with digestive problems. Peppermint or ginger tea or ginger ale would be good choices for "clear liquids". Try adding nutmeg to your food or drinks. Studies have shown that calcium supplements helped relieve diarrhea in people taking nelfinavir (Viracept). This might work for diarrhea caused by other medications. THE BOTTOM LINE Diarrhea is a common problem for people with HIV. It is usually caused by an infection in the digestive system. Stress, some medications, or problems digesting milk products can also cause diarrhea. The most serious result is dehydration. This is more of a problem for children than for adults. If you have diarrhea, you should drink plenty of clear liquids. Some simple changes in your food can help with diarrhea. So can some over the counter medications or acidophilus. Be sure you tell your health care provider if your diarrhea lasts more than a few days. source: The AIDS Infonet

WHY IS NUTRITION IMPORTANT? NUTRITION GUIDELINES FOR PEOPLE WITH HIV PRACTICE FOOD SAFETY WHAT ABOUT SUPPLEMENTS? THE BOTTOM LINE FOR MORE INFORMATION WHY IS NUTRITION IMPORTANT? Good nutrition means getting enough macronutrients and micronutrients. Macronutrients contain calories (energy): proteins, carbohydrates, and fats. They help you maintain your body weight. Micronutrients include vitamins and minerals. They keep your cells working properly, but will not prevent weight loss. Good nutrition can be a problem for many people with HIV. When your body fights any infection, it uses more energy and you need to eat more than normal. But when you feel sick, you eat less than normal. Some medications can upset your stomach, and some opportunistic infections can affect the mouth or throat. This makes it difficult to eat. Also, some medications and infections cause diarrhea. If you have diarrhea, your body actually uses less of what you eat. When you lose weight, you might be losing fat, or you might be losing lean body weight like muscle. If you lose too much lean weight, your body chemistry changes. This condition is called wasting syndrome or cachexia. Wasting can kill you. If you lose more than 5% of your body weight, it could be a sign of wasting. Discuss it with your doctor. NUTRITION GUIDELINES FOR PEOPLE WITH HIV First, eat more. Extra muscle weight will help you fight HIV. This is very important. Many people want to lose weight, but for people with HIV, it can be dangerous. Make sure you eat plenty of protein and starches, with moderate amounts of fat. Protein helps build and maintain your muscles. Meats, fish, beans, nuts, and seeds are good sources. Carbohydrates give you energy. Complex carbohydrates come from grains, cereals, vegetables, and fruits. They are a "time release" energy source and are a good source of fiber and nutrients. Simple carbohydrates, or sugars give you quick energy. You can get sugars in fresh or dried fruit, honey, jam, or syrups. Fat gives you extra energy. You need some – but not too much. The "monounsaturated" fats in nuts, seeds, canola and olive oils, and fish are considered "good" fats. The "saturated" fats in butter and animal products are "bad" fats. A moderate exercise program will help your body turn your food into muscle. Take it easy, and work exercise into your daily activities. Drinking enough liquids is very important when you have HIV. Extra water can reduce the side effects of medications. It can help you avoid a dry mouth and constipation. Remember that drinking tea, coffee, colas, chocolate, or alcohol can actually make you lose body liquid. PRACTICE FOOD SAFETY It’s very important to protect yourself against infections that can be carried by food or water. Be sure to wash your hands before preparing food, and keep all of your kitchen tools and work areas clean. Wash all fruits and vegetables carefully. Don’t eat raw or undercooked eggs or meat, and clean up juices from raw meat quickly. Keep leftovers refrigerated and eat them within three days. Check the expiration date on foods. Don’t buy them or eat them if they’re outdated. Some germs are spread through tap water. If your public water supply isn’t totally pure, drink bottled water. WHAT ABOUT SUPPLEMENTS? Some people find it difficult to go shopping and prepare meals all the time. Supplements can help you maintain your body weight and get the vitamins and minerals you need. Don’t use a product designed to help you lose weight, even if it says it contains everything needed for good nutrition! Your health care provider can help you choose a supplement that’s right for you. Vitamin and mineral supplements can be very helpful. They are discussed in Fact Sheet 801. THE BOTTOM LINE Good nutrition is very important for people with HIV. When you are HIV-positive, you will need to increase the amount of food you eat and maintain your lean body weight. Be sure to eat a balanced diet, including plenty of protein and whole grain foods, with some sugar and fat. An exercise program will help build and maintain muscle. Drink plenty of liquids to help your body deal with any medications you are taking. Practice food safety. Keep your kitchen clean, wash foods, and be careful about food preparation and storage. If your tap water isn’t pure, drink bottled water. If you feel you need to use nutritional supplements, be sure to get some expert advice from your health care provider. FOR MORE INFORMATION You can get more information on nutrition and HIV from the following: A Clinician’s Guide To Nutrition In HIV and AIDS, by Cade Fields-Gardner and others, published by the American Dietetic Association, $26 plus $5 shipping and handling: The American Dietetic Association, P.O. Box 97215, Chicago IL 60678-7215; or 800-877-1600, ext. 5000. Eat Up! Nutrition Advice and Food Ideas for People Living with HIV and AIDS by Charlie Smigelski, RD, $10.00, https://www.eatupbooks.com/hivbooks.html Nutrition and HIV: A New Model for Treatment by Mary Romeyn, MD, $18.95, published by Jossey-Bass, Inc, telephone 415 433 1740. Fact sheets on HIV nutrition are available at https://www.larklands.net source: The AIDS Infonet

WHAT IS FATIGUE? IS FATIGUE IMPORTANT? HOW DO I KNOW IF I HAVE FATIGUE? WHAT CAUSES FATIGUE, AND HOW IS IT TREATED? THE BOTTOM LINE WHAT IS FATIGUE? Fatigue is tiredness that does not go away when you rest. It can be physical or psychological. With physical fatigue, your muscles cannot do things as easily as they used to. You might notice this when you climb stairs or carry bags of groceries. With psychological fatigue, it may be difficult to concentrate for as long as you used to. In severe cases, you might not feel like getting out of bed in the morning and doing your regular daily activities. IS FATIGUE IMPORTANT? Fatigue is one of two main ways the body warns you about a problem. The other warning is pain. Most of us pay attention to pain, and stop whatever causes us pain. We don’t pay as much attention to fatigue. One reason might be that fatigue sneaks up on us: it usually gets worse so slowly that we don’t even notice. People with HIV and fatigue tend to get sicker faster than people without fatigue. Also, ongoing fatigue can weaken the immune system. People with HIV should find out what is causing their fatigue and treat it. HOW DO I KNOW IF I HAVE FATIGUE? Fatigue can start and increase very slowly. If you feel tired even after you rest, talk with your health care provider about fatigue. Give your health care provider as much information as possible. This will make it easier to know if you are fatigued, and what might be causing it. The following questions are good to think about before you talk to your health care provider about fatigue: How long have you been tired? Compared to a few months ago, how has your activity level changed? When are you tired? Is it after certain activities, like climbing stairs? Do you wake up tired? How do you feel when you are tired? Are you short of breath? Are your muscles sore? Is it difficult to concentrate or remember? Is it hard to get interested in your daily activities? Are you sleeping well? How long do you sleep each night? How many times do you get up? Is it hard to fall asleep or stay asleep because of itching, pain, or other problems? WHAT CAUSES FATIGUE, AND HOW IS IT TREATED? Fatigue can be caused by many different factors. Work with your health care provider to find the cause of your fatigue and the best way to treat it. Active HIV infection. When HIV multiplies rapidly, your body uses a lot of energy trying to fight it. Most people have more energy after they start taking antiretroviral medications (ARVs). Other active infections. Other infections can tire you out, even without obvious symptoms. Parasites in your digestive system, bronchitis, other infections or allergies can cause fatigue. If these infections are treated, your energy should improve. Poor nutrition. People with HIV need more energy than healthy people. If you are not getting enough nutrients, your energy level will be low. Diarrhea can rob your body of nutrients and cause fatigue. See Fact Sheet 554 on diarrhea, 800 on nutrition, and 801 on vitamins. If possible, meet with a dietitian who knows about HIV disease to discuss your eating habits. For some people, vitamin B12 supplements or better nutrition can eliminate fatigue. Anemia (see Fact Sheet #552). The main job of the red blood cells is to carry oxygen from the lungs to the rest of the body. If you don’t have enough red blood cells, or if they aren’t carrying enough oxygen, your fatigue may be caused by anemia. A simple blood test will show whether you have anemia. If you do, your health care provider will determine what is causing anemia. It could be due to blood loss, damage to your bone marrow caused by ARVs or vitamin deficiencies, or by a low level of the hormone erythropoietin which helps make red blood cells. Low hormone levels. Especially in men, low levels of the sex hormone testosterone can cause fatigue and lack of interest in sex and other normal activities. Low levels of other important hormones such as DHEA (see Fact Sheet 724), cortisol or thyroid can cause similar problems. Hormone levels can be checked with blood tests. Pills, patches, creams, or injections can restore hormone levels to normal. Depression (see fact sheet 558). This is more than just feeling sad. Chemical changes in the brain can cause fatigue and a lack of interest in daily activities. There is no blood test for depression. The chances that you are depressed are higher if you have previously been diagnosed with depression, if you have a history of heavy alcohol or recreational drug use, or if you have a family history of emotional disorders. Depression can be treated with medications. However, some antidepressants can cause problems with sexual functioning. Also, some antidepressants interact with some ARVs, so they must be used very carefully. Lifestyle. Getting enough sleep is important. Habits like smoking or drinking a lot of coffee can make it harder to sleep. Regular exercise can make it easier to sleep. THE BOTTOM LINE Fatigue is a very common condition for people with HIV. Untreated fatigue can make HIV disease progress faster. It can be very difficult to figure out the cause of fatigue. Several different factors can cause the same symptoms. Blood tests can identify some causes but not others. The more information you can give your health care provider, the easier it will be to determine what is causing your fatigue and how to treat it. source: The AIDS Infonet

SIDE EFFECTS OF ANTIRETROVIRAL MEDICATIONS (ARVs)? BLOOD SUGAR BLOOD FATS See Fact Sheet 121 for information on the Complete Blood Count and Fact Sheet 122 for tests included in the Chemistry Panel. For information on normal laboratory values, see Fact Sheet 120. SIDE EFFECTS OF ANTIRETROVIRAL MEDICATIONS (ARVs)? Standard blood tests measure blood sugar (glucose) but not blood fats. People with HIV are testing their blood sugar and blood fat levels more frequently because ARVs seem to cause abnormally high levels. This is especially true for the ARVs called protease inhibitors. For more information, see Fact Sheet 553 on lipodystrophy (body shape changes). BLOOD SUGAR Glucose is sugar. It is broken down in the cells to provide energy. Blood sugar increases after you eat or drink anything besides water. A high glucose level (hyperglycemia) can be a sign of the disease diabetes mellitus. High blood sugar levels can eventually damage your eyes, nerves, kidneys or heart. High blood sugar can be a side effect of the HIV protease inhibitors. Low blood sugar (hypoglycemia) can cause fatigue, but there are other more common causes of fatigue for people with HIV. In a healthy person, blood sugar is controlled by insulin. Insulin is a hormone produced by the pancreas. It helps glucose move from your blood into your cells to produce energy. High blood sugar levels could mean that your pancreas is not making enough insulin. However, some people make plenty of insulin, but their bodies don’t respond normally. This is called "insulin resistance." In either case, the cells don’t get enough glucose to use for energy, and glucose builds up in your blood. Some people who take HIV protease inhibitors develop insulin resistance and can have high blood glucose levels. This condition is sometimes treated with the same medications used to treat diabetes. There is no simple blood test for insulin resistance. There are three ways to test for blood glucose levels: A random blood glucose test. This measures the glucose in a sample taken when you have been eating on your usual schedule. A fasting glucose test. This uses a blood sample taken when you have not had anything to eat or drink (except water) for at least 8 hours. A glucose tolerance test. This starts with a fasting glucose test. Then you are given a measured amount of glucose in a sweet drink. Glucose is measured in several more blood samples taken at specific time intervals. If your blood glucose is too high, you might have diabetes. Treatment for diabetes involves weight loss, diet and exercise. It can also involve medications or insulin shots. BLOOD FATS Fat is a source of energy. It carries some vitamins around the body. It is used to make hormones and cell membranes, to protect organs and to lubricate some moving body parts. However, too much fat in the blood increases the risk of heart disease or pancreatitis. Triglycerides are the most common form of fat in the body. Cholesterol is another form of fat. In order for fats to be carried in the blood, they are wrapped in protein molecules. These bundles of protein-wrapped fat are called lipoproteins. Lipoproteins come in different sizes. Smaller ones are called low-density lipoproteins (LDL) or very-low-density lipoproteins (VLDL). These molecules carry fats from the liver to other parts of the body. Too much LDL or VLDL can cause fat to build up on the walls of your arteries. This can reduce the oxygen supply to your heart muscle and cause heart disease or a heart attack. Larger lipoproteins are called high-density lipoproteins (HDL). These are called "good" lipoproteins because they remove fats from your arteries and return them to the liver for more processing. High levels of HDL seem to protect people from heart disease. Blood fats are measured as the amount (in milligrams) contained in one tenth of a liter (a deciliter) of blood, or mg/dL. Measuring Triglycerides Triglyceride levels in the blood rise quickly after you eat. You cannot eat for at least 8 hours before you give a blood sample. Many people with HIV disease have unusually high levels of triglycerides. This is especially true for people taking protease inhibitor drugs. Triglyceride levels under 150 are considered normal. Levels greater than 1000 mg/dL can cause pancreatitis. Measuring Cholesterol Total cholesterol includes the "bad" low-density and the "good" high-density lipoproteins. Total cholesterol does not change too quickly after you eat, so you can give blood any time for this test. Total cholesterol levels below 200 are considered good, and levels over 240 are considered bad. HDL Cholesterol is good cholesterol. It can be measured in a non-fasting blood sample. Higher levels of HDL cholesterol are better, and levels over 40 are considered good. LDL Cholesterol is bad cholesterol. LDL levels are calculated using a formula that includes the level of triglycerides. You need a fasting blood sample to measure triglycerides or to calculate LDL cholesterol. Levels below 100 are good, and levels over 160 are considered a high risk for heart disease. A recent analysis of clinical trials found that, for very high risk patients, LDL should be lowered to no more than 70. HIV health care providers are treating more of their patients with high cholesterol levels, especially if the patients have a family history of heart disease. If your cholesterol level is high, discuss treatment options with your health care provider. source: The AIDS Infonet