Therapeutic drug monitoring is infrequently performed outside research settings at present. Given that this is a new and investigational area of HIV management, it seems unlikely to become widely available very quickly.

At present, British treatment guidelines recommend TDM in circumstances where doses other than those recommended by the manufacturer are being used. It is also recommended in cases of severe liver impairment, and to manage toxicity. In patients with high peak levels but no current evidence of toxicity, dosage reduction may be a strategy to prevent the development of toxicity.

High peak levels or high drug exposure with the following drugs are associated with toxicities:

• Ritonavir and triglyceride elevations, circumoral paraesthesia, diarrhoea

• Indinavir and kidney stones, colic and other urinary tract/kidney problems associated with indinavir crystals

• Efavirenz and central nervous system toxicities such as vivid dreams, anxiety and feeling `stoned`.

Other adverse effects of therapy have not been clearly linked with high drug levels.

Drug interactions such as between methadone and protease inhibitors, or between NNRTIs and protease inhibitors may also be grounds for recommending a test after starting treatment.

Finally, monitoring drug levels in young children, especially below the age of two, may be useful due to the wide variability in the metabolism of protease inhibitors and NNRTIs among this age group.

University of Liverpool

At present the only United Kingdom laboratory which performs therapeutic drug monitoring is the Department of Pharmacology and Therapeutics at the University of Liverpool, led by Professor David Back. The cost is relatively low - £60 per sample per drug (exclusive of transportation and handling costs). The turnaround time is two to three weeks. For further information contact Professor David Back or Sara Gibbons at the Department of Pharmacology & Therapeutics, University of Liverpool (Telephone 0151 794 5553). Their excellent website is at http://www.hiv-druginteractions.org

The drugs that are routinely monitored are: Amprenavir, atazanavir, indinavir, lopinavir, nelfinavir, ritonavir, saquinavir, nevirapine and efavirenz. Other drugs may be monitored by arrangement.

Roche is providing free therapeutic drug monitoring via the Liverpool University service for all patients when they start taking nelfinavir and/or saquinavir.

Merck Sharp and Dohme will fund the cost of therapeutic drug monitoring via the Liverpool University service in cases where individuals receiving indinavir treatment have suspected toxicities.

Further details of which drugs can be monitored and which drugs are covered by manufacturer grants can be found at: http://www.hiv-druginteractions.org/tdm/tdm_rou.htm