Choosing a Drug Combination

The ideal treatment for HIV is one that:

• effectively suppresses the virus -- that is, quickly reduces your viral load to an undetectable level and keeps it there as long as possible
• restores your CD4 counts
• has minimal side effects and long-term toxicities
• is easy to take (few pills with an easy schedule)

A single antiretroviral drug is not powerful enough to suppress HIV on its own; it has to be taken in combination with other antiretroviral drugs. Years of experience with dozens of different drug combinations has given us a huge amount of information on each combo, including overall survival rates, how it affects viral load and CD4 count, its side effects and long-term toxicities.

This leads us to suggest one more goal for the "ideal" combo: it should be easy to choose. The number of anti-HIV drugs, and the number of possible ways of combining them, is growing all the time. Fortunately, we know which combinations are best to start with. Earlier (see "How Do We Know Which Treatments Are 'Best'?"), we described how expert panels assemble the information from clinical trials into treatment guidelines. Guidelines usually rank drug combinations, often using terms such as preferred, alternate, and acceptable. A drug combination's ranking indicates how well it rates in terms of several criteria, including how well it suppresses viral load over the long term, the ease of its pill-taking schedule, and its risk of major side effects or toxicity.

This ranking system can help differentiate the multitude of possible combinations. It is meant to guide, not to replace, decisions made by you and your doctor. A so-called "alternate" combination is not necessarily "second best." It may turn out to be the best choice for you.

In the end, the ranking system aims to make the selection process much simpler. Rather than sifting through a bewildering number of possible options, HIV-positive people and their doctors can usually choose between a tried-andtested few, especially for first combinations.

Building a Combination

Antiretroviral drug combinations are built using drugs from different groups, or "classes." Each class of anti-HIV drugs attacks HIV in a different way. Researchers have discovered that it takes three different drugs from at least two classes to effectively suppress HIV. Clinical trials have taught us that an effective combination includes a "backbone" of two drugs from one class plus a third drug from another class.

If you want to know more about the different drugs in a combination or the theory behind how combinations are chosen, check out the appendices at the back of the guide.

• Appendix A shows how HIV replicates and how the different drug classes block the virus.
• Appendix B lists the antiretroviral drugs that are currently available in each class.
• Appendix C explains the theory behind combination treatment and describes how to build a combination.
• Appendix D lists drug combinations you might start with and some of the advantages and disadvantages of each combination.
• Appendix E explains drug resistance and resistance testing.

In this discussion of choosing a first combination, we will start by presenting the first-time combinations recommended at the time we published this guide. In the rest of this section, we'll concentrate on the factors to consider and the questions to ask when considering a new treatment combo. These will always be relevant even as the specific options vary over time.

First Combinations

Choosing your first combination is such an important topic that we think it is worthwhile to present the current information on recommended choices, even though recommendations may change over time. Knowing the currently preferred combinations will help you and your doctor make the best choice. You can contact CATIE (at 1-800-263-1638 or www.catie.ca) for the most up-to-date information.

A word about drug names before we start. Prescription drugs have two names: a common name, which describes the active ingredient in the drug, and a brand name, which is used to market the drug. (Brand names are always capitalized.) Antiretroviral drugs can be even more complicated because they are sometimes called by a three-letter abbreviation.

Also, some pills contain more than one drug. In this guide, we mention the common and brand names of each drug the first time we talk about it. After that, we use the most common name. If it all gets too confusing, Appendix B lists all the common and brand names of antiretroviral drugs currently available in Canada.

At the time this guide was published, most HIV treatment guidelines recommended the following first-time combinations:

• efavirenz (Sustiva) plus Truvada (tenofovir + FTC) -- also available together in one pill, called Atripla
• atazanavir (Reyataz) with a small dose of ritonavir (Norvir), plus Truvada
• darunavir (Prezista) with a small dose of ritonavir (Norvir), plus Truvada
• for pregnancy, Kaletra (lopinavir-ritonavir) plus Combivir (AZT + 3TC)

Some guidelines also recommend the following first-time combinations:

• Kaletra (lopinavir-ritonavir) plus Truvada
• fosamprenavir (Telzir) or saquinavir (Invirase) plus Truvada
• raltegravir (Isentress) plus Truvada
• any of the combinations listed above, with Kivexa (abacavir + 3TC) instead of Truvada

You can find more information about these drugs in the appendices (or in up-to-date fact sheets from CATIE or other sources).

Remember, that while these are the recommended combinations, this does not mean that other combinations are not as effective or that another combination may not be the best one for you. In the next section, we talk about some issues to consider as you and your doctor choose your drug combination. (Appendix D covers some more of the reasons why you might choose one combination over another.)

Which Combination Is Best for You?

Although choice can be a good thing, it can also be frustrating: "How should I know which to choose?" is a common complaint among HIV-positive people trying to pick a treatment combo. However, some of those decisions may already be made for you. Depending on your medical situation, some drugs may not be allowed or some may be more suitable than others.

Here are some of the most important things to consider. You may not know whether these apply to you, but you can use this list to bring up topics with your doctor.

Pre-Existing Resistance

Drug-resistant forms of HIV can sometimes be transmitted from person to person. Therefore, you may already be resistant to some medications even if you have not taken them before. Guidelines recommend that all HIV-positive people have a resistance test done before they start treatment. Resistance testing is not perfect, but it can identify specific drugs that may not work for you. This allows you and your doctor to choose other drugs that are more likely to work. (See the discussion of drug resistance in Appendix E.)

Hypersensitivity

You may be allergic, or hypersensitive, to certain drugs. For example, many people are hypersensitive to abacavir (Ziagen, also found in Kivexa and Trizivir). A simple blood test, done before you start treatment, can determine whether you're likely to have a potentially dangerous hypersensitivity reaction to abacavir (see the CATIE Fact Sheet on "Abacavir Hypersensitivity Screening" if you want more information on this subject). If so, you can cross it off your list of choices. You may also be hypersensitive to other antiretroviral drugs, so ask your doctor about the signs of a hypersensitivity reaction so that you can seek medical help should you react to a drug. There are no tests for any medication other than abacavir that will indicate a possible reaction.

Other Medical Conditions

• If you are pregnant or thinking about having a baby, you should not take efavirenz (Sustiva) because of concerns about its possible effects on the fetus. Many other antiretrovirals have proven safe for use during pregnancy.
• If your CD4 count is above a certain level, nevirapine (Viramune) is much more likely to cause liver toxicity. Nevirapine is not recommended in these cases.
• Certain drugs can raise cholesterol levels or otherwise put you at increased risk for cardiovascular disease. This may be acceptable if your cardiovascular risk is low to begin with. However, if you have risk factors for cardiovascular disease -- such as smoking, obesity, high cholesterol or a family history of stroke or heart disease -- it may be better to avoid these drugs.

Certain drugs may not be recommended if you have hepatitis B or C or other liver problems, kidney damage, tuberculosis, depression or other mental and emotional health issues.