Efavirenz blood levels: monitoring useful

Swiss researchers have reported on the use of drug level testing in people taking the anti-HIV drug efavirenz. People who experienced virological failure on the drug were more likely to have low levels of efavirenz in their blood than people whose viral load remained suppressed. High efavirenz blood levels were associated with an increased risk of central nervous system (CNS) side-effects. The authors suggest that dose adjustments made on the basis of therapeutic drug monitoring (TDM) should be investigated further in efavirenz users.

The study involved 130 people who had been taking efavirenz for more than three months in combination with other antiretrovirals. Eighty-five of these provided more than one sample; each sample being taken at three month intervals. The rate of virological failure in people whose blood levels fell into the lower range (below1,000ug/l) was over twice that seen in people with more moderate or high levels. CNS side-effects, such as light-headedness, feeling faint, drunk, or restless, were three times more common in people with high efavirenz levels (above 4000ug/l).

The study found a tenfold variation between individuals in efavirenz plasma levels, but concurrent protease inhibitor therapy did not appear to exert any significant effect on efavirenz levels. It is unclear how valuable therapeutic drug monitoring might be in dose adjustment to avoid side effects; in one case, a patient who experienced CNS side effects in the early months of therapy reported no problems after nine months on efvairenz, despite plasma levels of efavirenz above 10,000 ug/l at this time.

Missed doses are a frequent cause of inadequate drug levels, though one person in this study had very low efavirenz levels despite reporting good adherence. In the UK, TDM is offered by the HIV Pharmacology Group at the University of Liverpool. The cost of an efavirenz blood level test is £40 per sample plus transportation costs.