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Choosing a Drug Combination

January/February 2002

A note from Since this article was written, the HIV pandemic has changed, as has our understanding of HIV/AIDS and its treatment. As a result, parts of this article may be outdated. Please keep this in mind, and be sure to visit other parts of our site for more recent information!

How does your provider know which drugs to use when starting or changing a drug regimen? Which drugs are better? You may wonder why can't the doctor give you that "once-a-day drug" like your friends have. There are no easy answers to these questions, but you can help your provider choose a drug regimen that is best suited to fit your lifestyle. When a physician is faced with a choice of drug therapy for a patient, he or she has to look at many different factors specific to each patient. There are pros and cons to each combination, but ultimately, the patient is the person who has to take the medicine, and therefore has a huge role in deciding what is best for them.

Most clinicians use the guidelines set by the International AIDS Society U.S.A. (IAS) or those established by the U.S. Department of Health and Human Services (DHHS). They serve as the backbone for combining drugs for patients who have never taken drugs, or have only had some HIV drugs in the past. These guidelines are reviewed and updated regularly and give structure to a very complicated array of drug combinations, and considerations for HIV treatment in general.

Before we choose drugs for a patient, we must first decide if this is the right time to start medication. Is the patient mentally prepared for the commitment of near-perfect adherence? Can the patient delay therapy to a later date without damaging the chances for future treatment options? Some regimens -- as HIV drug combinations are commonly known -- work better when the viral load is low (under 100,000 for example). Other, more potent drugs will work even if the viral load is higher.

Assuming we have considered these issues, how then do we narrow down the list? Providers need to evaluate drugs based on how potent they are. If a patient has a very high viral load, the drugs chosen need to be strong enough to get the viral load down to an undetectable level as quickly as possible. If the drugs chosen are not tolerated (they may cause side effects and adverse reactions) the patient may not take the medication as prescribed. This will set up the person taking the drugs to possibly fail the regimen due to poor adherence. Could there be drug interactions with other prescriptions given for other medical problems? (This is a great reason to use only one pharmacy, and tell the pharmacist the over the counter and prescription medications you take.)

Moreover, each patient should be evaluated for drug resistance if possible. Even before a newly diagnosed patient begins medication, it is possible for that patient to be resistant to certain medication. This is because the virus could have been exposed to many drugs in the individual who infected the new patient and is therefore transferring drug resistance. In those people who have had some HIV drugs in the past, the medical provider must determine if resistance to the previous drugs or similar drugs has occurred. This can be determined by a physician's best guess or by blood tests called genotype and phenotype. Finally, in some clinics, the cost of the medications can be a factor. Because of limited financial resources, only some drugs are available in some settings, and prescribing doctors are allowed to use only certain drugs when coming up with a combination that will work.

Drugs available to treat HIV today are classified in three different groups, based on the activity of the drugs and the way they work to stop HIV replication. The classes are nucleosides (including the nucleotide), non-nucleosides, and protease inhibitors.

PI and 2 NRTIs
Long-term data
Effective and durable
Can save NNRTIs
Cross-resistance between PIs
Strict complex dosing
Variable drug levels between patients
Possible long-term metabolic disorders
Dual PI and NRTIs
Better blood levels
Can save NNRTIs
Possibly more effective and durable
Less drug needed
Potential for lower cost
Potential broad class resistance
Possible long-term metabolic disorders
Possibly increases stress on the liver
PI-sparing regimen
Good blood levels
Simple regimen
Fewer pills and frequency
Cross resistance to entire class
Not all are equivalent
Triple NRTIs (Trizivir and possibly in the future 2 NRTIs plus Viread)
Saves PI and NNRTI
Simple regimen
Potency and durability not proven Less effective at high viral loads Potential for greater mitochondrial toxicity
3 mechanisms of action
Combined potency
Maintenance possible
Useful in advanced disease
PI/NNRTI drug interactions
Multi-class resistance with limited options
Additive toxicities

Glen Pietrandoni is director of Clinical Pharmacy Services for the Walgreen Specialty Pharmacy, focusing on HIV, located in the Howard Brown Health Center of Chicago.

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A note from Since this article was written, the HIV pandemic has changed, as has our understanding of HIV/AIDS and its treatment. As a result, parts of this article may be outdated. Please keep this in mind, and be sure to visit other parts of our site for more recent information!

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This article was provided by Positively Aware. It is a part of the publication Positively Aware. Visit Positively Aware's website to find out more about the publication.
See Also
More on HIV Medications
More on HIV Treatment