Therapeutic Drug Monitoring (TDM) May Detect Drug Failure
Are your antiretroviral drugs being properly absorbed into your body in order to suppress HIV?
If antiretroviral therapy is not working in an individual who is 100-percent adherent to the regimen, drug monitoring of antiretroviral drugs may determine if the lack of treatment response is due to inadequate drug concentrations. Recent studies have suggested that the failure to achieve adequate plasma (one of the components of blood) levels of antiretroviral drugs may contribute to lack of treatment success.
Poor adherence, poor absorption, metabolism, elimination, drug interactions and other reasons may explain why adequate drug concentrations are not reaching the virus. Individual differences in body chemistry limit the effectiveness of treatments for some. Therapeutic drug monitoring (TDM) for antiretrovirals is one way to address this issue, but there is much debate regarding its usefulness in routine clinical care.
Establishing the relationship between plasma concentrations and antiviral effects for both nucleoside reverse transcriptase inhibitors (NRTIs) and nonnucleoside reverse transcriptase inhibitors (NNRTIs) is difficult since their anti-HIV effects are not accurately measured by analyzing plasma concentrations. Certain target concentrations, however, are associated with improved antiviral effect for protease inhibitors (PIs).
The levels a drug achieves in plasma varies between individuals as well as within the same individual.
For example, your drug levels may be different in the morning than in the afternoon, and your drug levels may also be different than those of another person who is on the same regimen. Reasons for these fluctuations include drug-to-drug interactions, drug-to-food interactions and problems of adherence.
The significance of TDM for PIs in the treatment of HIV infection has yet to be completely understood and no routine standardized test for TDM exists. The potential benefits and limitations of using TDM for monitoring the antiviral effects of PIs, however, can be summarized as follows:
Benefits of TDM
Limitations of TDM
Despite these facts, some people feel that TDM of antiretrovirals is probably of minimal value for treating individuals and that less attention should be placed on drug levels. These individuals believe more effort should be focused on developing new drugs and strategies which achieve plasma levels well above the maximum concentration to suppress HIV.
Although monitoring of PI concentrations is not standard in routine clinical care, it may still play an important role in other aspects of HIV management, such as evaluating drug-to-drug interactions and perhaps periodically assessing adherence.
Use limited for now
Although TDM tests are commercially available, their widespread use will be limited until a standardized, accurate and inexpensive method to measure drug actions in the body is available.
In general, these tests are expensive ($150 to $200), limited to selected sites, and may not be available for all approved and investigational drugs for which an individual may be receiving. Before insurance companies pay for the service, they must be convinced that TDM is useful.
In order to carefully interpret any results, clinicians must have a thorough understanding of the pharmacokinetics and pharmacodynamics (the physiological effects of drugs and the mechanisms of their actions) of PIs. Studies now under way will address the clinical utility of TDM.
This article has been reprinted at The Body with the permission of AIDS Project Los Angeles (APLA).
This article was provided by AIDS Project Los Angeles. It is a part of the publication Positive Living.