Drug levels and HIV

July 2001     View PDF     En español

Therapeutic drug monitoring

TDM is an area of intense interest as several small studies have shown that people with higher drug levels are more likely to have better and more sustained anti-HIV responses. Further, early results from a larger study known as ATHENA has also shown the benefits of TDM. Read the box below more information.

TDM involves drawing a blood sample to measure the amount of a particular protease inhibitor and/or non-nucleoside reverse transcriptase inhibitor (NNRTI). Most experts believe that measuring the levels of nucleoside analogue reverse transcriptase inhibitors (NRTIs) will be of little value as they block HIV inside the cell. Drug levels found in blood may not necessarily compare to those inside cells.

TDM may be particularly useful for protease inhibitors as their blood levels can vary greatly among individuals as there are differences in how people break down (metabolize) these drugs. Ensuring that people stay within a “therapeutic range” may greatly improve the likelihood of a lasting anti-HIV response. TDM may also help determine the proper dose of a drug for a particular person.

Right now, most anti-HIV drugs are given in standard doses whether someone weighs 120 pounds or even 250 pounds. Many experts believe that this is one of the reasons why women experience more side effects as they generally weigh less than men. As a result, TDM may not only help prolong anti-HIV response, but it may also help minimize side effects.

Furthermore, standard doses are given to people regardless of their stage of disease. But since people with more advanced disease generally have liver and/or kidney dysfunction, different doses may actually be needed. People co-infected with hepatitis may also need a different dose.

The “therapeutic range” may differ for someone just starting therapy than for someone who has already taken different drugs and has developed resistance to them. People with drug-resistant virus may need to achieve higher drug levels in order to “overcome” the resistant virus. This can be achieved by taking higher doses or using a boosting drug like ritonavir (Norvir). For more information, read the Drug Interactions section.

A few hurdles still have to be overcome before TDM can be used as part of routine medical care. One is about the tests themselves. When companies develop a new drug, they or a company they work with will develop a test to measure drug levels. More often than not, these companies do not publish how they developed these tests. So if university based researchers want to measure levels of that particular drug, they develop their own tests, and there’s no way of knowing whether these new tests are as accurate as the original one. This is also true for most of the TDM tests now being offered by commercial laboratories.

Perhaps the bigger hurdle is determining the proper time to draw the blood sample. Different people taking the same drug will have a different pattern in how it gets absorbed by and eliminated from their bodies. In other words, everyone has a different drug level profile. This is especially true for children, as younger children eliminate drugs more rapidly than older children, and they in turn eliminate faster than adults.

For anti-HIV drugs, the Cmin is probably the most important level when looking at anti-HIV response. In this case, you would need to have your blood drawn right before you take your next scheduled dose. In practice, this would be very difficult to do. The more likely scenario is that people go for blood draws whenever they can get an appointment, and this may not be right before their next scheduled dose.

As a result, several groups are trying to map out drug levels over a 12- or 24-hour period, hoping they can use this information to predict what the Cmin might be for someone who took his or her drugs two hours before their blood draw. Furthermore, for someone more concerned about side effects, the Cmax will be more important and the same dilemma would exist around the time of the blood draw.

Some experts propose that TDM may be an effective way of measuring adherence. But others disagree, because a “non-adherent” person could take a dose of drug before going in for their blood draw and drug levels would then be detected. The assumption here is that he or she is taking meds as prescribed, even though in reality that may have been the only dose they took during the week.

Introduction

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Drug levels inside cells