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.

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:

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)

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.

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.

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.

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)

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.

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.

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.

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.

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) .