HIV is a virus that can multiply quickly in your body. Even though no cure exists for HIV infection or the later stage of HIV disease known as AIDS, there are many different drugs that can slow down the virus, and we know that the slower the virus grows, the longer people live and the healthier they remain. Most people who take medicine for their HIV infection can now expect to live healthy lives for many years.

Without treatment, however, HIV can make your immune system very weak. Your immune system is what allows your body to fight off bacteria and viruses. When it is weakened, you will have a hard time staying well.

Deciding to start taking anti-HIV drugs is a very personal choice, and one that cannot be made alone. It is important to talk with your VA doctor, who can help you make a wise, appropriate decision.

This lesson can help you decide:

• Whether to start therapy (http://www.hiv.va.gov/treat-01-01)
• What drugs to take (http://www.hiv.va.gov/treat-02-00)
• Whether to continue therapy (http://www.hiv.va.gov/treat-03-00)

Deciding whether to start therapy

Though HIV drugs can be lifesavers, there are reasons NOT to start taking them right away. For one thing, the virus sometimes becomes resistant to drugs. That means the virus has changed in a way that makes the drug no longer work. The most common cause of drug resistance is not taking medications correctly. The longer you are on a drug, the more likely the virus will develop resistance to it. Also, all drugs have side effects, some of them long-term. For these reasons, it can be best to wait to start therapy, as long as you and your doctor monitor your condition, so that you can start therapy before your immune system becomes too weakened to protect you. In general, experts say you should think about these four things: Symptoms of HIV disease (also called your clinical status, or how well you feel) Your CD4 count and viral load Whether or not you have AIDS Whether you can and will stick to your treatment plan (called adherence) We will look at each of these more closely. Symptoms (clinical status) "Clinical status" refers to how well you are doing in general, including how well you feel. Your doctor will look at whether you have symptoms of HIV disease. These symptoms are signs that HIV is weakening your immune system, and include things such as weight loss, chronic fevers, and opportunistic infections. (Opportunistic infections--also called OIs-- are infections that happen in someone with a damaged immune system.) CD4 count and viral load Even though you may not feel it, when you have HIV, the virus and your immune system are at war with each other. The virus is trying to grow as fast as it can, and your body is trying to stop it. Two tests, the CD4 count and the viral load, help you and your doctor know how strong your immune system is, and know whether it is keeping HIV under control. CD4 cells play a major role in helping your immune system work properly. HIV causes disease by killing off CD4 cells. It does this by infecting the cells and turning them into virus factories, a process that kills the cell. A test called the CD4 count can tell you how many CD4 cells you have. The higher the number, the better. The test, however, doesn't tell you if those CD4 cells are working properly. The viral load test indicates how much of the HIV virus is present in your blood, and how fast it is growing. The higher the viral load, the faster HIV is infecting and killing your CD4 cells. The lower the viral load, the better. Your doctor will look at these two things carefully. People whose CD4 count is low, and people whose viral load is high, are more likely to get sick sooner than people with a high CD4 count and low viral load. CD4 count and viral load tests usually are done every 3 months. Results can help you and your doctor decide when it's time to start taking anti-HIV drugs. The U.S. Department of Health and Human Services makes general recommendations regarding when HIV-positive people should start taking HIV drugs. These are not firm rules, just guidelines. It's clear that if your CD4 count is below 200, or if you have severe symptoms, you should start therapy. Whether or not you have AIDS The term "AIDS" describes the condition of having an immune system that has been seriously damaged by HIV disease. To be diagnosed with AIDS, you have to meet one of three criteria: Having a CD4 count that is less than 200 Having one of several illnesses or symptoms known as "AIDS-defining illnesses," (http://www.hiv.va.gov/vahiv?page=cm-105_disease#t-3) which cause serious problems only in people with severely weakened immune systems Having both a CD4 count less than 200 AND an AIDS-defining illness Most experts agree that anyone with AIDS should take anti-HIV drugs, unless there is some reason why taking anti-HIV medications would make that person sicker. Whether you can and will stick to your treatment plan (adherence) It is very important to start drug therapy only when you are ready to make a strong commitment to sticking to a drug therapy plan (or regimen). With some drug regimens, you will need to take pills several times a day, every day! In order for the drugs to work and keep working, you must follow the directions for taking them very carefully. If you're not sure you can do this, you might need help in finding ways to stick to the plan. If you are wondering whether you should start taking drugs for HIV, you should sit down and talk with your VA health care provider as soon as possible. Depending on your specific needs, your doctor can come up with a personal treatment plan for you.

Summary chart

The following table shows how you can monitor your symptoms, CD4 count, and viral load to help decide whether it is time to start anti-HIV medications: Symptoms CD4 Count Viral Load Recommendation AIDS-defining illness severe symptoms (such as unexplained fever or diarrhea for more than 2 to 4 weeks) Any value Any value Start HIV drugs No symptoms Less than 200 Any value Start HIV drugs No symptoms Higher than 200 but less than 350 Any value Consider treatment but weigh the pros and cons No symptoms Higher than 350 Higher than 100,000 Most doctors will hold off on starting HIV drugs, but some will decide to treat No symptoms Higher than 350 Less than 100,000 Hold off on starting HIV drugs

Once you and your doctor have decided that you should start taking drugs for HIV, your doctor will come up with a personal treatment plan for you. You will find it easier to understand your plan if you learn about the different drugs available and what they do.

Print out these questions to ask your doctor (http://www.hiv.va.gov/treat-questions1) when you start to discuss particular drugs.

What kinds of drugs are available?

Anti-HIV drugs are also called antiretroviral drugs or antiretrovirals. They work because they attack the HIV virus directly. The drugs cripple the ability of the virus to make copies of itself. There are 5 main classes of anti-HIV drugs: Nucleoside Reverse Transcriptase Inhibitors (NRTIs or "nukes") Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs or "non-nukes") Protease Inhibitors (PIs) Fusion or Entry Inhibitors Chemokine Coreceptor Antagonists (CCR5) Integrase Inhibitors Each group attacks HIV and helps your body fight the infection in its own way. Most of these drugs come as pills, capsules, or coated tablets. Several of these drugs may be combined into one tablet to make it easier to take your medications. These are known as fixed-dose combinations. The following is a short description of how each group of drugs works and the names of the drugs. A new group of antiretrovirals is on the horizon: integrase inhibitors. Since this group is still in the experimental phase, and not yet widely available, we won't go beyond mentioning it here. Note: The names of drugs are long and sometimes hard to pronounce. Don't worry! You can always come back and read this again, and you can talk to your VA doctor about questions you have. Nucleoside reverse transcriptase inhibitors (NRTIs or nukes) The first group of antiretroviral drugs is the nucleoside reverse transcriptase (say "trans-krip-tase") inhibitors (NRTIs). NRTIs were the first type of drug available to treat HIV. They remain effective, powerful, and important medications for treating HIV when combined with other drugs. They are better known as nucleoside analogues or "nukes." When the HIV virus enters a healthy cell, it attempts to make copies of itself. It does this by using an enzyme called reverse transcriptase. The NRTIs work because they block that enzyme. Without reverse transcriptase, HIV can't make new virus copies of itself. The following is a list of the drugs in the NRTI class: Emtriva® (emtricitabine) Epivir® (3TC, lamivudine) Retrovir® (AZT, zidovudine) Videx-EC® (ddI, didanosine) Viread® (tenofovir) Zerit® (d4T, stavudine) Ziagen® (abacavir) Several of the NRTI drugs may be combined into one tablet to make it easier to take your medications. These drugs are known as fixed-dose combinations: Combivir® (Retrovir + Epivir) EpzicomTM (Epivir + Ziagen) Trizivir® (Retrovir + Epivir + Ziagen) Truvada® (Viread + Emtriva) Non-nucleoside reverse transcriptase inhibitors (NNRTIs or non-nukes) The second type of antiretroviral drugs is the non-nucleoside reverse transcriptase inhibitors (NNRTIs). These drugs are sometimes called non-nucleosides or "non-nukes." These drugs also prevent HIV from using reverse transcriptase to make copies of itself, but in a different way. Three NNRTIs are available: Rescriptor® (delavirdine) Sustiva® (efavirenz) Viramune® (nevirapine) Protease Inhibitors (PIs) The third group of drugs is the protease (say "pro-tee-ase") inhibitors (PIs). Once HIV has infected a cell and made copies of itself, it uses an enzyme called protease to process itself correctly so it can be released from the cell to infect other cells. These medicines work by blocking protease. Nine PIs are available: Aptivus® (tipranavir) Crixivan® (indinavir) Invirase® (saquinavir) Kaletra® (lopinavir + ritonavir combined in one tablet) Lexiva® (fosamprenavir) Norvir® (ritonavir) PrezistaTM (darunavir) Reyataz® (atazanavir) Viracept® (nelfinavir) Note: Many PIs are recommended or approved for use only with low-dose Norvir, which "boosts" their effect. Fusion or entry inhibitors The fourth group of antiretrovirals is called fusion or entry inhibitors. These medicines work by stopping the HIV virus from getting into your body's healthy cells in the first place. Only one fusion inhibitor is available at present, and it needs to be injected: Fuzeon® (enfuvirtide, T-20) Chemokine Coreceptor Antagonists (CCR5) To infect a cell, HIV must bind to two types of molecules on the cell's surface. One of these is called a chemokine coreceptor. Drugs known as chemokine coreceptor antagonists block the virus from binding to the molecules. SelzentryTM (maraviroc)

Now that you have learned a little about the types of drugs that are available and how they work, you may be wondering how your VA health care provider will know which medicines you should take.

Anti-HIV drugs are used in combination with one another in order to get the best results. The goal is to get the viral load as low as possible for as long as possible.

Anti-HIV medicines do different things to the virus--they attack it in different ways--so using the different drugs in combination works better than using just one by itself.

Except in very special circumstances, anti-HIV drugs should never be used one or two at a time. Using only one or two drugs at a time can fail to control the viral load and let the virus adapt (or become resistant) to the drug. Once the virus adapts to a drug, the drug won't work as well against the virus, and maybe it won't work at all.

Experts haven't come up with one combination of HIV medications that works best for everyone. Each combination has its pluses and minuses.

When drugs are used together, it is called combination therapy (or HAART, highly active antiretroviral therapy).

Combination therapy

So, how will your doctor know which combination to choose? You and your VA doctor can consider the options, keeping certain things in mind, such as possible side effects, the number of pills you'll need to take, and how the drugs interact with each other. Print out these questions to ask your doctor (http://www.hiv.va.gov/treat-questions2) if you are considering combination therapy.

"Adherence" refers to how well you stay on your treatment plan--whether you take your medications exactly as your VA health care provider tells you.

If you follow your doctor's instructions about how to take your medicine, the anti-HIV drugs can work well to lower the amount of virus in your blood. Taking your drugs correctly increases your likelihood of success.

But, if you miss doses, or don't follow a regular schedule, the level of the drug in your body goes up and down. The virus then has the opportunity to make copies of itself more rapidly. That increases your viral load.

Following your treatment schedule also helps to stop drug resistance. If you miss a dose, the virus may make new and different types of itself that the drug can no longer combat.

It's challenging for some patients to stick to their drug treatment plan. Most plans involve taking several pills every day, and many of the drugs have unpleasant side effects.

Questions to ask about each drug

One of the most important things you can do to make sure you take your medicine correctly is to talk with your doctor about your lifestyle, such as your sleeping and eating schedule. If your doctor prescribes a drug, be sure and ask the following questions (and make sure you understand the answers): What dose of the drug should be taken? How many pills does this mean? How often should the drug be taken? Does it matter if it is taken with food, or on an empty stomach? Does the drug have to be kept in a refrigerator? What are the side effects of the drug? What should be done to deal with the side effects? How severe do side effects have to be before a doctor is called? During every visit to your doctor, you should talk about whether you are having trouble staying on your treatment plan. Studies show that patients who take their medicine in the right way get the best results: their viral loads stay down, their CD4 counts stay up, and they feel healthier.

Before you start a treatment plan, you should:

• Do a "trial run." Practice your treatment plan. You can pretend that jelly beans or mints are your drugs.
• Get your doctor to write everything down for you: names of the drugs, what they look like, how to take them (with food or not), and how often to take them. This way, you'll have something to look at in case you forget what you're supposed to do.
• With your doctor's help, develop a plan that works for you.

It is important that you tell your doctor right away about any problems you are having with your treatment plan. Keeping a medication diary can help you remember any problems you have.

Now that you've gone over some of the things you should think about before starting HIV drug therapy, let's look at some of the things you will need to know once you are taking the medicine. These involve drug interactions and drug side effects.

What are drug interactions?

Your anti-HIV medications can be affected by other medicines, including other prescription drugs you are taking and drugs you buy over the counter at a drugstore. Even herbal therapies and some things found in common foods can affect your HIV medicines. When one drug affects how another drug behaves, this is called a drug-drug interaction. For example, some drugs become less effective when taken together. When something in food affects how a drug behaves, it is called a drug-food interaction. For example, grapefruit juice, taken at the same time as certain drugs, can boost the amount of these drugs in your bloodstream to an undesirable level. Everyone taking anti-HIV drugs needs to be very careful about these interactions. Luckily, many of these interactions are well known to your provider, and can be managed. Your VA health care provider can give you a list of drugs and foods to avoid, depending on what kind of medicine you are taking. Ask for this information for each drug that you are taking. Also, be sure that you tell your doctor about every single medication, drug, and herb you are taking--whether you got them by prescription or not.

What are side effects?

Medicines can cause changes (or effects) in the body. Some effects, like making you feel better, are the ones that you want and expect to happen. Other effects are ones that you don't want or don't expect. The effects that you don't want or expect are called side effects. Almost all medicines have side effects. Some people take aspirin for a headache, but it gives them an upset stomach. The upset stomach is a side effect of the aspirin. Not all side effects are unpleasant, though. Even the side effects that make you feel sick aren't always bad. Some side effects mean that your medicine has started to work. Your doctor will try to prescribe the amount of anti-HIV medicine that is high enough to fight the HIV virus, but low enough to avoid causing too many side effects. How do you deal with side effects? Side effects can be hard to deal with. One way to cope with them is to know what to watch out for and have a plan to deal with problems that come up. That's why you need to talk to your VA doctor about the risk of side effects from different drugs, before you start therapy. At the beginning of any treatment, you go through a period of adjustment--a time when your body has to get used to the new drugs you're taking. Sometimes you'll have headaches, an upset stomach, fatigue, or aches and pains. These side effects may go away after a month or so. If you notice any unusual or severe reactions after starting or changing a drug, report the side effects to your doctor immediately. More information is available in the Side Effects Guide. (http://www.hiv.va.gov/treat-04-00)

How do you know if the drugs are working?

After you've started taking medicine for your HIV, your doctor will look at how much virus is in your bloodstream (your viral load) to see how well the drug therapy is working. If the medicines are working, your viral load goes down. You will have less of the virus in your bloodstream. Other ways you and your doctor can see if the drugs are working are: Your CD4 count. This number should stay the same or go up if your drugs are working. Your health checkups. Your treatment should help keep you healthy and help you fight off infections and diseases.

Should you ever take a 'holiday' from the drugs?

Sometimes, your doctor may suggest that you take a break or a "drug holiday" from your anti-HIV medicine. HIV patients may go on a drug holiday for a number of reasons, such as trying to control side effects. Taking a break from drug treatment is a very complicated issue that is still being studied by the experts. In general, the most recent research suggests that taking an antiretroviral drug holiday for reasons other than a severe reaction to medications is harmful to your health. Be sure to talk with your VA health care provider about this issue if you have questions about it. How you stop taking your anti-HIV drugs safely can be a complicated process. Remember, just skipping doses without your doctor's instructions is dangerous, and you should never change your treatment plan without talking with your doctor.

Should you ever switch the drugs you're taking?

You should never change the drug plan you're on without talking with your doctor. This is a very important decision and one that must be made with your VA health care provider. If you are following your drug therapy plan correctly (taking the right medicines in the right amount at the right time), but the treatment is not working well enough, your doctor may consider switching your medicines. Your doctor also may want to change your medicine if the side effects are too severe (this is called drug toxicity). Before changing medicines, you and your VA doctor should talk about: All the anti-HIV drugs you have taken before and the ones you haven't taken How strong are the new drugs that your doctor recommends Side effects that may go along with the new medicines How well you will be able to follow the new drug treatment plan Always be sure to talk with your doctor about any changes in your drug treatment.

What if viral load is undetectable?

If your viral load becomes undetectable (doesn't show up on tests), can you stop treatment? Having an undetectable viral load, meaning that the virus isn't showing up on tests, is a sign that the anti-HIV medications are working. It doesn't mean that you can stop treatment. If you stop treatment, the virus will start reproducing again, and your viral load will increase. Even though the virus is undetectable in the blood, it is still hidden in other parts of your body, such as the brain, reproductive organs, and lymph nodes. Researchers don't know if the amount of virus in the blood is similar to the amount that might be in other organs.

What if your treatment isn't working?

Even when a person has tried different combinations of drugs, the treatment plan doesn't always work. This often occurs because the drugs don't completely stop the virus from reproducing. As the virus makes copies of itself, changes (or mutations) sometimes occur. These changes may result in a new strain of the virus that is resistant to the action of the drugs. Sometimes, your provider can do a blood test (called a genotype or a phenotype) that can help show which drugs the virus has become resistant to. This can help identify other drugs that might still work against your virus. Even if a virus is resistant to most or all available drugs, some people can still stay healthy by continuing to take the same combination of drugs. Therefore, you should discuss the situation with your doctor rather than just stop taking your medications. If a person has a strain of HIV that is resistant to most or all available drugs, that person may want to consider joining a clinical trial that is testing new drugs that have not yet been approved by the U.S. Food and Drug Administration (FDA). See Clinical Trials (http://www.hiv.va.gov/treat-05-00) .

Almost all medicines have side effects, including medicines for HIV. Always let your doctor know if your side effects are severe, especially if you are finding it difficult to stay on your treatment plan.

The following is information on some common side effects and tips on how to deal with them.

Anemia means you have a low red blood cell count. The red blood cells take oxygen to different parts of the body, and when your body is short of oxygen, you feel tired.

Many people with HIV have anemia at some point. HIV can cause it; so can some of the anti-HIV drugs.

To see if you have anemia (a symptom of anemia is feeling tired, fatigued, or short of breath), your VA health care provider can do a simple blood test. If you are anemic, food or other medicines can help.

Diarrhea is common in people with HIV, and it can be caused by some anti-HIV medicines. Diarrhea can range from being a small hassle to being a serious medical problem. Talk to your VA health care provider if diarrhea goes on for a long time, if it is bloody, if it is accompanied by fever, or if it worries you.

When you have diarrhea, always be sure to replace the fluids you have lost by drinking ginger ale, broth, herbal tea, or water.

You can also ask your doctor about taking medicines to help with your diarrhea.

Certain HIV medicines can cause dry mouth, making it difficult to chew, swallow, and talk.

Treating dry mouth can be simple--start by drinking plenty of liquids during or between meals. If your dry mouth is severe or doesn't go away, talk to your doctor about prescribing a treatment for you.

Many people feel tired, especially when they are stressed or their lives are busier than usual. Symptoms of being tired can include: having a hard time getting out of bed, walking up stairs, or even concentrating on something for very long.

If the tiredness (or fatigue) doesn't go away, even after you have given your body and mind time to rest, this tiredness can become a problem. It can get worse if you don't deal with it.

Talk with your VA health care provider if your fatigue is not going away or is becoming too hard to deal with. The more information you can give your doctor about how you are feeling, the more likely the two of you will be able to come up with the right treatment for your fatigue.

Many people lose their hair as they get older, or when they are going through a very stressful time in their lives.

You can also lose your hair from taking certain medications, including those used to treat HIV.

The most common cause of headaches is tension or stress, something we all have from time to time. Medications, including anti-HIV drugs, can cause them, too.

Headaches usually can be taken care of with drugs you can buy without a prescription, such as aspirin. You can also help to prevent future headaches by reducing stress.

Certain medications used to treat HIV can cause nausea. They make you feel sick to your stomach and want to throw up. This usually goes away a few weeks after starting a new medication.

Call your doctor if you vomit repeatedly throughout the day, or if nausea or vomiting keeps you from taking your medication.

HIV itself and some medications for HIV can cause damage to your nerves. This condition is called peripheral neuropathy. When these nerves are damaged, your feet, toes, and hands can feel like they're burning or stinging. It can also make them numb or stiff.

You should talk to your VA doctor if you have pain like this.

Some medications can cause skin problems, such as rashes. Most rashes come and go, but sometimes they signal that you are having a bad reaction to the medication.

It's important that you check your skin for changes, especially after you start a new medication. Be sure to report any changes to your VA health care provider.

Weight loss goes along with some of these other side effects. It can happen because of vomiting, nausea, fatigue, and other reasons.

Talk with your VA health care provider if you're losing weight without trying, meaning that you're not on a reducing diet.

A clinical trial is a research program that tests a new medicine to see if it is safe and works well. When a new medicine (or drug) is first discovered, you cannot get it by prescription. Researchers must first test it in a laboratory with animals. Then, they must do a clinical trial in a hospital or clinic to test it in people. They test it to see if it is safe and to see how much of the medicine (or what dose) is enough to work.

The Food and Drug Administration (FDA) (http://www.fda.gov) is a government agency that decides if a new drug is safe enough to give to patients by prescription. It looks at the results of the clinical trials to make this decision. Testing drugs for HIV is very important, and clinical trials are a way to find new and better medicines. All medicines that you can now get for HIV were first tested in clinical trials.

Clinical trials follow a set of rules called a protocol. The protocol says who can participate, how long the study is, and which tests need to be done.

Clinical trials are managed by doctors and are usually run by nurses or other health care professionals. The clinical trial staff will follow your progress closely and can help tell your regular doctor what is happening with your treatment.

Trials are also checked by an institutional review board (IRB). This is a group of people who reviews the clinical trial regularly to protect your rights, safety, and well-being.

When you are in a clinical trial, you may need to see the doctor more often and sometimes stay overnight in the hospital. This is because they want to check the effects of the medicine carefully. Because clinical trials are research, they will often test the real drug against a placebo (or sugar pill). Usually you will not know if you are taking the medicine or the placebo until the clinical trial is over.

Before you start a clinical trial, you will go through a screening process. This is to make sure that it is safe for you to start taking the medicine. The staff will ask you about your health history, and you may have a blood test, urine test, or others (such as a physical exam or a heart test).

You will also go through a process called informed consent. The doctors and nurses will explain exactly what will happen during the clinical trial. They will answer your questions and tell you about the risks and benefits of the clinical trial. They will ask you to sign a document called a consent form. When you sign this form, you are saying that you understand what is going to happen and that you agree to participate. Even after you have started a clinical trial, you are free to quit at any time for any reason. Quitting early will not affect your medical care in the future.

No. It will not cost you anything because you are helping the researchers to test a new medicine. Sometimes you may even get extra money to pay for your time or travel.

Clinical trials can last from a few weeks to several months. After the treatment is over, they will usually ask you to come back for some follow-up visits. The follow-up period may be as short as a few weeks or as long as six months and helps to make sure that you are safe.

There are four different types of clinical trials: Phase I, Phase II, Phase III, and Phase IV.

It usually takes about 10 years for a drug to be developed and approved for prescription. Many people would like to take the newest medicine as soon as it is proven to work. However, even after a drug has been successful in a Phase III trial, it still may take six to 12 months before that drug is approved for prescription.

Trials are paid for by government agencies, pharmaceutical (or drug) companies, individual doctors and hospitals, or clinics. The doctors and nurses will tell you who is paying for the study before you begin a trial.

Often, people want to join a clinical trial because their treatment isn't working. Not everyone can join a trial, though. Most clinical trials have eligibility criteria. These are rules about who can participate, based on health, age, and maybe other things. For example, some trials take only people who have a particular viral load or CD4 count. Usually, you can't participate in a clinical trial if you have any infections or are using medicines that might make it hard to measure how well the test treatment is working. You also cannot participate if the test treatment might harm you.

If you do qualify for a trial and decide to participate, you should be willing to follow the guidelines of the study.

Before you start a clinical trial, you should think about the positive and negative things that may happen. In addition, keep a list of questions to ask before joining a trial. (http://www.hiv.va.gov/treat-questions3)