Most strategic decision-making processes begin by formulating a list of questions to consider. Some of the answers can only come from you; others your doctor can help answer. Several important questions about starting anti-HIV therapy are included here.
|Questions to Help You Build Your HIV Treatment Strategy|
Some anti-HIV drugs interact with oral contraceptives (i.e., The Pill). More detailed information on these interactions may be found in Project Inform's publication, "Drug Interactions." It may be necessary to adjust the dose of the contraceptives or use other methods for birth control.
If you have determined that you are ready to start anti-HIV therapy, there are some clear guidelines that can help you make an informed decision about which medications to use.
There are four different classes of anti-HIV drugs approved for use. These are:
The November 2003 Federal Guidelines list the following two combinations as "preferred" first-line regimens, because they are believed to have good potency and are easy to take:
The Guidelines also list more than a dozen other alternative combinations that may be less potent, carry a somewhat higher side effect profile, have to be taken more often or that require taking more pills.
Not all "alternative" combinations, however, are equal. In fact, several are likely to be better than others and may be nearly equal to the "preferred" regimens. These include using:
FTC is a newly approved drug, likely to be interchangeable with 3TC. Tenofovir is also a newer drug. Since it works against most NRTI resistant virus, some recommend saving it for use in second- and third-line combinations.
Trizivir (AZT + 3TC + ABV) is the only approved triple nucleoside combination available in one pill. This combination can be taken alone, without combining it with drugs of any other class. There is concern, however, that Trizivir may not be as potent for first-line therapy as other combinations, particularly in people whose viral load is very high (more than 100,000). Since future combinations may depend on at least one or two of these three drugs in order to work effectively, using Trizivir as first-line therapy can significantly impact future available options. For these reasons, Trizivir may only be an appropriate first-line option in situations where a person requires an extremely simple regimen or cannot tolerate NNRTIs or PIs.
While the Guidelines recommend efavirenz over nevirapine, there are occasions where nevirapine may be a more attractive choice. This is particularly true for people who wish to save protease inhibitors for later, but who are concerned about the neurological (brain-related) side effects of efavirenz. Pregnant women and women trying to get pregnant should avoid efavirenz and may consider nevirapine a better option. Women in general shouldn't feel a particular benefit to choosing nevirapine over efavirenz, but women who are pregnant or trying to conceive need to be aware of the risks of efavirenz use during pregnancy.
All of the NNRTIs are highly cross resistant with one another, meaning that when the virus becomes resistant to one it will likely be resistant to the others, making them less useful. Of the three drugs in this class, delavirdine is used least often. This is because it must be taken three times per day and has interactions with a number of other medications.
Other protease inhibitor combinations may be used as first-line therapy, but most require that a low dose of ritonavir be added as a booster so that they become more potent and are able to be taken less frequently and at lower doses. Aside from Kaletra, other ritonavir-boosted PIs have not been well studied for first-line therapy use.
Some data show that when a person starts anti-HIV therapy using a protease inhibitor, they will likely be able to use efavirenz successfully as second-line therapy. There are less data on the reverse scenario. There are even fewer data showing the long-term therapy implications of starting a combination with three NRTIs together, like Trizivir. Developing a longer-term treatment strategy requires weighing the theoretical risks and benefits.
When a person's virus develops a high level of resistance to one drug in a specific class, it will generally have at least some resistance to the other drugs in that class. This is called cross resistance. When resistance occurs, it causes the drug to be less potent. Thus, even with more than twenty approved drugs, it is only possible to come up with two or possibly three highly potent combinations in a row.
Some believe that the best first-line strategy is to take whatever is most potent. Studies so far indicate that the most powerful and durable effects come from a person's first combination. The longer a person can stay on his or her first combination without significant side effects or resistance developing, the better. If a person can go five years or longer, the hope is that more new drugs will have been approved in the meantime, which will allow a greater number of second- and third-line therapy options. Kaletra is considered the most potent and durable first-line anti-HIV medication.
Others feel that saving potent and longer lasting medications for second-line therapy is the better strategy. Starting with a combination containing an NNRTI or only NRTIs is likely to work well for many people and spares protease inhibitors for later. It is hoped that the NNRTI and NRTIs will have fewer long-term side effects. The theory has merit, but there are no studies to prove that this is the superior long-term strategy.
Whichever choice you make, it's probably wisest to have a good fall-back strategy if your first combination doesn't work as well as you hoped. Decide in advance what your definition of treatment failure is and what your next combination will be.
Your doctor may have strong opinions about when to start therapy or which combination they think will be best for you. Your opinion and your concerns count too. Share them with your doctor so that he or she can help you build the best treatment strategy for you. Project Inform's publication, "Building a Cooperative Doctor/Patient Relationship," offers a number of tips for building a relationship with your doctor that works best for you.
Because it is your life and your body that will be affected, only you can ultimately decide how you wish to balance the need to keep your virus in control with potential risks for HIV disease progression and side effects of medications. Remember to ask questions: of yourself, your doctor, other people living with HIV and information sources like Project Inform. Take your time, be prepared and then enjoy life to the fullest, knowing you have made the best decision you possible could have.
|Federal Guidelines' Recommendations for When to Start Anti-HIV Therapy|
|Symptoms||CD4+ Cell Count||Viral Load (Plasma HIV RNA)||Recommendation|
|Severe symptoms, AIDS defining illnesses||Can be any number||Can be any number||Strong recommendation to treat with anti-HIV therapy|
|Either severe symptoms or no symptoms at all||Less than 200||Can be any number||Strong recommendation to treat with anti-HIV therapy|
|No symptoms||More than 200, but less than 350||Can be any number||Treatment should be offered, though some controversy exists|
|No symptoms||350 or more||More than 55,000||Although up to 30% of people in this category may have disease progression if left untreated, there are not yet data to prove conclusively that treating now is beneficial in the long term|
|No symptoms||350 or more||Less than 55,000||Most would not recommend anti-HIV therapy, as the risk of progression (15%) is low|
|No symptoms or acute retroviral syndrome||More than 200||Can be any number -- can go as high as millions of copies||Primary HIV Infection (detectable viral load, but HIV antibodies are negative or indeterminate): Treatment may be offered, but benefits of treating now are still theoretical -- no data exist to prove long term clinical benefit|
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