Diving into the world of HIV treatment for the first time can be intimidating: dozens of meds, lab tests, medical terms and differing opinions that may make you feel like you need to go to medical school in order to make the right decisions.

You don't. Whether you've just been diagnosed with HIV, have known for a while, or are helping a friend with HIV, the good news is that you can learn enough to make informed decisions without becoming an infectious disease specialist. The trick is to take it step by step, learning enough along the way to put it all together with the help of an experienced health care provider.

Make no mistake: study after study has shown that people with HIV (or any serious illness, for that matter) do best when they are in the care of a specialist. So this guide is in no way meant to supplant the advice of a professional. But a good provider will welcome an informed patient. One thing that AIDS activism taught the health care profession is that involved consumers are to be embraced rather than feared. The goal of "health literacy" is to forge a partnership between doctor and patient -- one in which decisions are made by mutual consent. This leads not only to better choices, but also to stronger buy-in from patients, leading to better long-term adherence to treatment -- critical in HIV care.

One of the important concepts of health literacy is that learning needs reinforcement. When I hear a difficult medical concept the first time, it can be hard to grasp. The second time I hear it, I say, "Hmm -- I've heard that before ..." And the third time, I think, "Oh, I know that already!" The point is not to feel stupid if you don't grasp the information presented here on first reading. Put it down and take a second look a few days later. Or go to some of the resources given at the end of this piece and look for similar information presented in a different way. Most people find that with repeated access these concepts are understandable.

Some people don't feel the need to be involved in all the treatment choices their health care provider recommends, at least at first. If that's you, just make sure you're seeing a provider who is well-recommended and who has a lot of experience treating people with HIV. And be sure to ask questions so you at least understand what's being recommended. You want to follow your doctor's advice because you agree with it, not just because you're told to.

A Brief History of HIV Treatment

One of the best ways to understand the current state of HIV treatment is to know how we got here. When the Human Immunodeficiency Virus (HIV) was found to be the cause of AIDS, an aggressive search began for medications that could control it. The National Cancer Institute began a massive screening effort of existing drugs to see which could limit HIV's ability to replicate in vitro (in the test tube).

One of the first drugs found was a failed cancer chemotherapy treatment known only by its chemical name, azidothymidine (AZT). When mixed with HIV-infected blood, it was very effective at preventing HIV from replicating. But many things are quite effective in vitro. Bleach works beautifully in the test tube, but you can't drink bleach! So the next step was to try it in people.

AZT Monotherapy

In one of the first AIDS clinical trials, people took either AZT or a placebo (dummy pill). Six months later, 19 people on placebo had died, but only one on AZT. While this was exciting, there were two problems.

First, those on AZT took it five times a day. At that high dose, many people had such severe side effects that they could not tolerate the drug. Second, we now know that when people take a single HIV drug (monotherapy), it lowers the amount of HIV in the body by about 70%. While that seems impressive, there's a problem: 30% of the HIV in the body remains, and it can change, or mutate, and become resistant. Once HIV becomes resistant to a drug, that drug can no longer control the virus -- and when taking only one drug, this often happens within six months to a year. So, people taking AZT at this toxic dose had a lot of side effects like nausea and anemia, became resistant within a year, and sometimes died. It looked like the AZT was killing them, but in reality taking a single drug wasn't enough, no matter how much you took.

Since AZT alone wasn't working, trials began in the early 1990s in which people added a second drug like Epivir (3TC) to a lower dose of AZT (now taken only twice a day). When these two drugs were taken together, they lowered the amount of HIV in the body by 95%, with fewer side effects. This was an improvement, but the 5% of HIV that remained was still able to mutate and become resistant. It would take two to three years instead of six months, but the drugs would still stop working eventually.

HAART

The big change came in 1995, when researchers added a third drug, called Crixivan, to the mix. To their astonishment, they found that when people took three HIV drugs, they could lower the amount of HIV in their body by up to 99.99%! And, if they could get their viral levels that low and keep them there, the drugs might be able to work indefinitely. This became known as "combination therapy" or HAART (Highly Active Anti-Retroviral Therapy).

HAART changed everything. AIDS care now centered not on treating the many infections people got as their illness advanced, but rather on helping them take HAART correctly so the virus could not mutate and become resistant. And this is the major challenge facing people with HIV today: getting and maintaining an undetectable viral load.

A viral load test is a blood test that measures the amount of HIV in the blood. Numerous studies have found that in order to control HIV in the long run, a person usually needs to have their viral load drop below 50 copies per mm³ (cubic millimeter -- a few drops of blood). While this is called an undetectable viral load, it does not mean the virus is gone from the body -- only that there is so little of it in the blood that a viral load test can't find it. (People with undetectable viral loads can still transmit HIV to others.)

Early on, researchers hoped that HAART could eradicate all the HIV from the body within two years -- a cure! Well, they soon revised that estimate to four years, then to eight years, and finally to 78 years! The problem? HIV "hides" in certain cells that the drugs cannot penetrate. Since these cells live many decades, as soon as a person goes off HIV meds, the virus begins reproducing again and viral loads almost invariably shoot back up.

So, people with HIV now face two major questions: Do I need to be on HIV meds, and if I do, how can I prevent my virus from becoming resistant to the drugs? Neither question is easy to answer, unfortunately.

When to Start?

As with many things about HIV and AIDS, this is a difficult question with different answers for different people. Let's start with what we know:

First, not everyone needs to be on HIV meds. Experience has taught us that the "hit hard, hit early" approach popular after HAART appeared is not the best option for most people. Long-term side effects and the possibility of resistance have led most experts to recommend waiting to start HIV meds until they're needed.

Some people find this hard to accept: If I have a virus in my body and there are drugs that can control it, why not take them as soon as possible? Well, actually, everyone lives with many viruses and other foreign microbes in their bodies and they never need drugs to control them. In fact, 90% of the cells in your body are not human -- they are bacteria, parasites, and other microbes that are just "hitching a ride" in your gut. They don't do damage, and some even help you stay alive. Your immune system controls the ones that could do harm.

So, it's not unusual to live with a virus in your body -- the trick is to keep it under control. And most people's immune system can control HIV for many years without the help of drugs. So, if you don't need 'em, why take 'em? The important thing is to know when to start.

The most commonly used test to determine when to start HIV meds is the CD4 count. CD4 cells, also known as T4 cells or Helper cells, are an important part of the immune system: they tell all the other immune cells when to go to work. Without enough CD4 cells, all the other immune cells receive no instructions and can't fight off infections and cancers. A CD4 count above 500 is considered healthy, but most people who don't have HIV have a count somewhere around 1,000 (remember, that's 1,000 per mm³ -- they actually have trillions of CD4 cells.)

So most experts feel that people with HIV who have a CD4 count above 500 don't need to start HIV meds -- the immune system is able to control HIV on its own. But once the CD4 count drops below 200, many studies have shown that the risk of getting a serious infection like PCP (a potentially lethal pneumonia) increases dramatically. There is strong clinical proof that if you have a CD4 count below 200 you will most likely live longer if you start HIV meds. If your CD4 count is approaching 200, you should seriously consider starting HAART, along with other drugs, like Bactrim to prevent PCP.

The trickier question is about people whose CD4 counts are between 200 and 500, which includes many people with HIV. For years, the U.S. Public Health Service recommended that anyone with a CD4 count below 500 should start HIV meds, but in 2001 those guidelines were revised. Now, it is recommended that anyone with a CD4 count below 350 or with a viral load above 100,000 start the meds, regardless of whether there are symptoms of HIV disease.

But it's not just about "magic numbers" like 350 or 100,000. Some people with high viral loads are able to maintain high CD4 counts, and some people with high CD4 counts have serious symptoms that mean it's time to start treatment. The important thing is to watch the trend of your lab tests over time. In the chart below, Jack should probably start HIV meds because his CD4 count has been dropping every year. But Jill may choose to wait even though she is below 350, since she been relatively stable over time.

In order to keep track of your trends, it's a good idea to save a copy of each lab test you get. Over time, this will give you a good indication of what's happening in your body.

Watching Your Labs

For many people, HIV is not a disease of symptoms, but of numbers on a lab report. It's quite possible to have HIV for many years with no symptoms whatsoever. Unfortunately, you can't trust what your body is telling you. Even though they feel healthy, people with a low CD4 count can get seriously ill very quickly. So, people with HIV need to get regular CD4 and viral load tests even if they feel great, and to trust the reports.

If you want to get reliable lab results, here are some tips:

• Go to the same lab every time, for consistency.

• Go at the same time of day (CD4 counts vary during the day).

• Don't go right after vigorous exercise -- it can temporarily raise CD4 counts.

• Don't go if you have an infection -- wait three weeks after any infection or vaccination, since they can raise your viral load temporarily.

• Get a good night's sleep before the test, and try to lower your stress level!

If you see that your CD4 count is falling each time (a drop of 100 per year is not uncommon), most experts agree it is best to start HAART before the count hits 200. Likewise, if your viral load is rising each time, that may indicate it's time to start the meds.

What to Start With?

With 20 drugs now approved to fight HIV, it can seem like there are endless combinations from which to choose. In reality, time and research have shown that certain drugs and certain combinations work best, while others have fallen into disfavor. Zerit, for example, once a popular drug, is not commonly used as a first-line treatment anymore since it was found to cause changes in body shape more often than some other drugs. Rescriptor is similarly unpopular, since it is not as effective as other drugs and must be taken three times a day. And certain drugs don't mix well, so that narrows the choices further.

HIV drugs currently fall into four basic classes:

Nukes
(NRTIs: nucleoside reverse transcriptase inhibitors)
Emtriva, Epivir, Retrovir (AZT), Videx, Viread, Zerit, Ziagen

Non-nukes
(NNRTIs: non-nucleoside reverse transcriptase inhibitors)
Rescriptor, Sustiva, Viramune

Protease inhibitors
Aptivus, Crixivan, Invirase, Kaletra, Lexiva, Norvir, Prezista, Reyataz, Viracept

Fusion inhibitor
Fuzeon

Combination pills
Combivir (Epivir & Retrovir)
Epzicom (Epivir & Ziagen)
Truvada (Emtriva & Viread)
Trizivir (Epivir, Retrovir & Ziagen)
Atripla (Emtriva, Sustiva & Viread)

If you want a detailed description of how each class of drugs works, check the resource links at the end of this piece.

Current guidelines recommend that people take an "anchor drug" (a non-nuke or a PI) along with two nukes, but your doctor may recommend a different combination based on your situation. (Since Fuzeon is an injection, it is used only by people who have become resistant to the other meds.) Choosing which meds to start with depends on which side effects you're most concerned about, if you are already resistant to any of the meds, and if once-a-day or twice-a-day dosing matters to you (HIV drugs that are taken three times a day are usually not used anymore).

There are four recommended anchor drugs: three PIs (Kaletra, Lexiva and Reyataz) and one non-nuke (Sustiva). People often choose their anchor drugs based on their most common side effects, which we'll discuss below. People often choose their nukes based on their convenience. There are three pills that combine two nukes: Truvada or Epzicom (once a day) and Combivir (twice a day), but your doctor may recommend taking other nukes individually. And you can usually switch if your first choice doesn't work out. Your doctor may also have a genotype test done before you start, to see if you have drug-resistant HIV.

Some people with HIV who don't need the meds yet choose to stay away from info about the meds, in a sometimes healthy denial. But learning about the meds before you need them gives you time to make the decision that's right for you, rather than doing it hurriedly once your CD4 count gets low. And since over 99% of people with HIV will need to go on meds at some point, knowing about the drugs that may eventually save your life may make you feel more secure about your long-term health.

Before You Start

Anyone starting any new drug, HIV-related or not, should ask these questions:

• What is the name of this drug?
  It's good to know the names of your meds -- that's the only way you're going to learn the details about that drug. And if you end up in the ER and are asked what meds you are on, answering "a blue one, a white one and a yellow one" is not going to be much help.

• Why am I taking this drug?
  It's important to know what each drug you take is meant to treat, and why you need to take it. If you're taking many pills, only some of them actually fight HIV -- the others could do one of a number of things: control or prevent other HIV-related infections, help with side effects, treat other conditions like high blood pressure, etc. Know which drug does which job.

• How do I take this drug?
  Be sure you understand how many pills to take and how often. Also ask if the drug can be taken with food. Some drugs must be taken on an empty stomach, and some must be taken with food. For many drugs it doesn't matter, but taking it with food may help with side effects. Ask if you can drink alcohol while on the drug or if there are any other restrictions (like staying out of the sun, for example). Also make sure you can take the drug at the same time as other drugs. For example, some HIV drugs cannot be taken with antacids or with herbs like St. John's Wort.

Side Effects

Some people with HIV avoid all the meds because of stories they've heard about their side effects. But the most important thing you should know about the side effects of HIV meds is that everyone is different. Just because your friend had a certain side effect, that doesn't mean you will. The only way to know for sure which side effects, if any, you'll have is to try the meds yourself. And if you do have side effects, many are manageable.

There are three important questions to ask about side effects:

• What are the common side effects of this drug?
  We've all seen the long list of side effects that are listed in the "package insert" that sometimes comes with a pill bottle. Most of those side effects are rare and will usually not be a problem. But some side effects are more common (like diarrhea for people on Viracept, or vivid dreams for those on Sustiva), and you should be prepared for those and know what to do if they occur.

• What are the serious side effects of this drug?
  Certain drugs can cause reactions that can be life-threatening if the drug is not stopped. Ask if there are side effects that should lead you to call your doctor, such as a rash from Ziagen or Bactrim. Continuing some drugs after certain side effects can be dangerous.

• What are the long-term side effects of this drug?
  Some drugs have side effects that don't show up for weeks or months, so ask if there are certain side effects you should keep an eye out for, like body shape changes or elevated liver enzymes (a sign of possible liver damage). Some drugs may require careful liver monitoring over time, so be sure to ask if you should arrange regular blood tests to check for these side effects.

When it comes to side effects, people fall into three groups. There are those who have virtually no side effects -- that isn't common, but it does happen. There are those who have persistent side effects that require them to switch their meds. But the vast majority of people will have some side effects at first, until their body adjusts to the drugs. Then the side effects usually lessen or go away completely. So it's important to give any new med you're taking a chance. For example, many people who take Sustiva have "vivid dreams" when they start the drug. If you give up after a few nights, you will miss out on a very effective HIV drug. But if you stick it out for a few weeks, most likely the dreams will stop or lessen.

When starting a new drug, ask what you can do to lessen the early side effects. People with HIV who have taken the same medication may also have tips, but remember that your experience may be different from theirs. Be sure to try any new drug for at least six weeks if you can. If you still are having unacceptable side effects, ask your doctor about stopping or switching.

Once you begin HAART, you should see your viral load drop dramatically within a few weeks -- if it hasn't, that combination may not be right for you, and your doctor may recommend a different combination. In most people the CD4 count will begin to rise, but it can take months before it increases significantly, depending on how quickly the body is able to replace the missing cells.

Resistance

As mentioned earlier, HAART is most effective when it suppresses HIV levels by over 99%. Lowering it by 95% or even 98% may not be enough to avoid resistance. If the level of HIV in the body rises above 50 copies per mm³ and stays there, the chance of resistance increases (although the drugs may still have benefit). This means people with HIV need to take nearly every dose of their HIV meds as prescribed.

Each drug has been studied to determine how much of it enters the bloodstream and how long it stays there. In the chart below, the first dose of a drug that is taken twice a day has been taken at 9 am (the solid line). Levels of the drug quickly rise to the highest level, or peak, and then slowly begin falling, reaching the lowest level, or trough, before the next dose is taken. But if the evening dose is missed (the dotted line), drug levels begin to fall, and the chance of developing resistance is greatly increased because there isn't enough drug in the body.

Missing one dose will not usually lead to resistance, but missing as few as three in a row or three a month can. It's best to think about ways to avoid missing doses (known as adherence) before you start taking HIV meds. When you find a combination that works for you with side effects you can tolerate, you don't want to lose it. Taking every dose won't guarantee that your meds will continue to work, but it will greatly increase the chance they will.

Learning More

This primer contains the basic concepts people with HIV need to understand how their meds work, but there is much more that can be learned. ACRIA has a variety of booklets available, as do other organizations. Check out the resources below to learn more.

AIDSinfonet.org
AIDSmeds.com
TheBody.com/treatment
ProjectInform.org

Mark Milano is an HIV Health Educator at ACRIA and is an Editor of ACRIA Update.