• Therapeutic Drug Monitoring: Does It Make a Difference?
  Authored by David Burger (Nijmegen, The Netherlands)
  Abstract PL8.1

The pharmacology session opened with a plenary talk by David Burger on therapeutic drug monitoring (TDM). Dr. Burger is definitely one of the leading experts in the field and his group has contributed much of our current understanding of TDM in HIV management.

Dr. Burger started his talk citing a number of studies that have clearly shown TDM to be of virological benefit in specific clinical situations, most notably in drug-naive patients receiving nelfinavir (NFV, Viracept) or indinavir (IDV, Crixivan). Although some evidence supports the use in drug-experienced patients and for other PIs and NNRTIs, this is less conclusive. Many important studies are currently being conducted to address those issues.

The remainder of the talk focused on what Dr. Burger referred to as "the ten commandments of TDM in HIV." A group of experts has developed a list of key concepts regarding the use of TDM in routine HIV management and coined them with the Biblical term. These were briefly described one by one by the speaker who mentioned they would soon be made available on the Web.

These note when and how an HIV clinician might best use TDM and highlighted a number of issues including:

• TDM is most beneficial for PIs and perhaps NNRTIs but currently not NRTI.

• A trough level taken at the end of a dosing period is best to use in regards to drug efficacy.

• A peak level may be best if assessing PI toxicity and a random sample can be used for NNRTI toxicity due to their long half-life.

• Results deviating far from the predicted level may be beneficial in detecting poor adherence.

• Patient characteristics and details regarding all medications and the exact timing of the blood draw are crucial when sending out a drug level.

• Laboratories vary in their precision in determining drug levels. Therefore information regarding the lab's participation in a quality assurance program should be considered before deciding which one to use.

• Levels should only be measured after drugs have obtained steady state. This is usually after about two weeks for most PIs and NNRTIs.

• If doses are adjusted, a follow-up drug level should be drawn to determine the result of the new dosage.

• TDM is of particular value in a number of clinical situations, including pediatrics, pregnancy, multiple medications, combined PI/NNRTI use, and severe renal/hepatic insufficiency.

• In heavily drug-experienced patients, combined use of resistance testing and drug-level determinations, coupled with advice from an HIV pharmacologist and resistance expert may help determine the optimal drug regimen and dosage for that specific patient. This may be of particular benefit in choosing which PI to use and at what dose.

The talk was indeed stimulating. In a number of European countries such as Britain, France and the Netherlands, TDM is gaining widespread use. Much remains to be learned about how best to use this diagnostic tool and how much benefit our patients will derive. Since this is much less expensive than other assays (such as resistance testing), it may be quite cost effective in some clinical situations.

I think it would be wise to consider finding a reliable lab and an expert HIV pharmacologist that can be consulted on the use of TDM considering our current knowledge, or to consider enrolling appropriate patients in a relevant clinical trial utilizing TDM.