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HIV Drug Resistance and Resistance Testing

2001

What Are Some of the Factors That Contribute to the Accumulation of Drug-Resistance Mutations During Therapy?

Don't forget the golden rule: the less virus there is in the body, the less likely it is that the virus will continue reproducing and mutating. A powerful antiretroviral regimen is the most effective way to keep the level of virus low -- preferably undetectable (< 50 copies/mL) -- and to delay additional mutations from occurring.

There are a number of factors that can prevent an antiretroviral drug regimen from being as powerful as it can be. These include:

Poor Adherence or Compliance

In order for antiretroviral drugs to work correctly, they must be taken exactly as prescribed. This means taking the correct number of pills each day, being careful to take them a certain number of hours apart, while at the same time following dietary requirements (see "Poor Absorption" below).

Skipping doses or not taking medication correctly can cause the trough level of an antiretroviral drug to decrease in the body. The trough level refers to the amount of drug left in a person's body just before another dose of the drug is taken by mouth. If the trough level becomes too low, HIV can reproduce more freely and accumulate additional mutations.

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According to a few research reports, an HIV-positive person must be more than 95% adherent with his or her antiretroviral drug regimen in order for it to continue working properly. This means missing less than one dose a month.

Poor Absorption

Not only must antiretroviral drugs be taken on schedule, they also need to be absorbed effectively into the bloodstream. A drug -- or combination of drugs -- that is not absorbed properly can result in trough levels that are too low and, ultimately, allow HIV reproduction and the accumulation of drug-resistance mutations.

Certain drugs have specific dietary requirements. For example, people taking standard doses of the protease inhibitor Crixivan must take the drug three times a day (every eight hours) on an empty stomach. This means not eating within two hours before or one hour after taking the drug. (Note: If Crixivan is taken in combination with Norvir, another protease inhibitor, food restrictions do not apply.) The same goes for people who take the buffered formulation of Videx (the tablets that need to be chewed or mixed in water). Conversely, the protease inhibitor Fortovase should be taken with food, preferably food containing a moderate amount of fat. If dietary requirements are not followed while taking any of these drugs, drug levels in the body will decrease.

People with HIV can also experience diarrhea and vomiting. These can cause antiretroviral drugs to be expelled from the gut too quickly, reducing the amount of drug absorbed into the bloodstream.

Varying Pharmacokinetics

Pharmacokinetics is a term used by researchers to mean how a drug is absorbed, distributed, metabolized, and removed from the body.

Even though two people might receive the exact same dose of a drug, the amount of drug may be higher in one person's bloodstream than in the other person's bloodstream. Factors that can contribute to this difference include their body weight, height, and age. Some people also process, or metabolize, drugs faster or slower than others do. This can speed up -- or slow down -- the rate at which a drug is cleared from the body.

It is important to remember that a drug's correct dose -- the dose dispensed by pharmacists -- is determined in clinical trials based on the average dose found to be safe and effective. In other words, some people may be able to keep their viral load undetectable using lower doses of the drug, while some people might require higher doses of the drug to keep their viral load undetectable.

In the future, healthcare providers may begin performing blood tests to measure the amount of drug in their patients' bodies. This is called therapeutic drug monitoring and it may help determine whether or not a person has a correct trough level of each medication to ensure that viral load remains low or undetectable.




  
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This article was provided by AIDS Community Research Initiative of America. Visit ACRIA's website to find out more about their activities, publications and services.
 

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