Doctors have not yet discovered a single combination of HIV medications that's best for everyone. Each combination has its advantages and disadvantages. Unfortunately, researchers can't compare the hundreds of possible combinations of individual medications. Instead, they usually try to compare combinations of classes of medications. Two class combinations are commonly researched and prescribed today for people starting HIV treatment:

• One NNRTI plus two NRTIs
• One "boosted" PI plus two NRTIs

Each of these combinations is known to fight HIV. How do you choose one?

You and your doctor can consider three major issues: whether the treatment regimen preserves your future choices (also known as "sequencing"), how powerful a combination it is, and what side effects it can cause.

Other factors important in making this choice include the number of pills you'll have to take and how often you'll have to take these pills (once or twice a day).

Preserving Your Future Options (Sequencing)

You have every reason to hope that your first treatment regimen will keep your HIV under control for years and years. However, sometimes a person's first regimen stops working. For this reason, one of the most important things you and your doctor should keep in mind is the need to "sequence" your medications -- that is, to choose a first regimen that will leave you with plenty of options should that first regimen stop working.

The most common reason for a treatment combination to stop working is "resistance." This means that the HIV in your body has adapted to one or more of the medications you are taking and, as a result, the medications no longer have the power to prevent your virus from multiplying inside your body.

Some people can even be infected with a strain of HIV that is already resistant to certain medications. (Before you start treatment, your doctor should perform a "resistance test" to determine whether this is the case with you.) Usually, though, resistance happens after you've begun treatment. The most common cause is when you don't take all of your HIV medications on time at least 95 percent of the time.

How will you know if your treatment regimen has stopped working? Take a look at the results of your T-cell count and viral load tests. If you've always been taking your treatment on time, your viral load should drop at least 90 percent within two months of beginning treatment. Within six months, it should drop so low as to be "undetectable" (fewer than 50 copies/mL), and then remain that way indefinitely.

If your viral load does not more or less follow this pattern, your treatment may not be working properly. Similarly, a drop in your T-cell count may be a sign that your regimen isn't working right. There may be other reasons for a drop in T-cell count, however -- a cold or other illness, for instance -- so be sure to talk with your doctor if you're concerned.

What does all of this have to do with sequencing? As we explained on the previous page, there are five classes of HIV medications. Medications within each class work similarly. So, if your HIV becomes resistant to one of your medications, it may become resistant to other medications in that same class, even if you've never taken those meds.

For example, if your regimen includes an NNRTI and the NNRTI you're using stops working, all other NNRTIs will have lost their ability to fight your virus. The situation is a little less black-and-white with other classes of HIV medications. For instance, when your virus becomes resistant to one NRTI or one protease inhibitor, it won't necessarily become resistant to all of them.

This is why sequencing is important. If your HIV does become resistant to the first medications you're prescribed, you want to feel confident that there are still plenty of medications left that your HIV will be vulnerable to.

Potency

Some combinations of HIV meds are more powerful than others, which can be useful if you have an especially high viral load or a particularly low T-cell count. These more potent combinations, according to the latest research and current treatment guidelines, consist of two NRTIs plus either one "boosted" protease inhibitor or one NNRTI. These combinations have been used successfully in people who have viral loads above 100,000 and low T-cell counts. Unboosted protease inhibitors and combinations that consist of only three NRTIs, like the combination drug Trizivir, have been found to be less potent.

Side Effects

Each drug within a combination brings a risk of side effects. Of course, not everyone will experience these side effects (listed in the "Once- and Twice-a-Day Medications" charts). Some side effects, like nausea, rash or fever, can appear soon after you begin taking your drug combination and last only a short time (usually a few weeks). Other side effects, like fatigue or fat loss, can take longer to appear and may take longer to go away.

Some health problems that people with HIV may experience include:

• Lipodystrophy, a condition in which specific parts of your body gain ("lipohypertrophy") or lose ("lipoatrophy") a large amount of fat. It is one of several problems doctors call "metabolic complications." It's still unclear if these complications are caused by HIV itself, specific HIV medications or the boost in the immune system that occurs during HIV therapy. Most studies seem to indicate that several factors work together to cause body shape changes in HIV-positive people. The newer HIV medications don't seem to cause body shape changes.

• High cholesterol or triglycerides (which can lead to heart disease) and insulin abnormalities (which can lead to diabetes). A multitude of studies have shown that many protease inhibitors, as well as some NRTIs and other HIV medications, can help cause these problems. However, newer drugs, such as the NRTI Viread and the protease inhibitors Lexiva and Reyataz, may be less likely to contribute to these problems. Researchers have also come to believe that other factors, such as whether a person smokes, is overweight or doesn't exercise, may play a more important role in such problems than HIV medications do.

• Lactic acidosis. Most NRTIs, especially Zerit and Videx, can cause a buildup of lactic acid in your body. Too much lactic acid may cause nausea, vomiting and liver damage that can, on rare occasions, be life threatening.

• Nerve problems. Some NRTIs (like Zerit and Videx), as well as HIV itself, can cause damage to parts of a person's nervous system, leading to tingling, burning and numbness in the hands and feet -- a disorder known as neuropathy.

• Diarrhea. Many HIV medications, particularly Viracept and Kaletra, can cause diarrhea and other stomach problems, particularly at the beginning of treatment.

• Psychological problems. Some medications, like the NNRTI Sustiva, may trigger depression, anxiety or unusual dreams. This may be an issue if you're already depressed or have a history of serious mental disorders. Usually, however, these side effects do not last long.

Ask your doctor for a complete rundown of the side effects that particular HIV medications may cause. Usually only a small percentage of people experience any of the side effects described here or in the "Once- and Twice-a-Day Medications" charts. It's impossible to predict which side effects you will experience (if any), or if you will have problems managing them. Certain side effects are easier to handle than others. Fortunately, the majority of side effects don't last more than the first month or two after starting a medication.

No matter what, if you feel anything unusual -- whether it's mentioned in this booklet or not -- be sure to tell your doctor or nurse right away. However, never stop taking your medications or change the way you're taking your medications without first speaking with your doctor. If you stop treatment too suddenly or start skipping doses, you might accidentally cause drug resistance.

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