Up to one third of patients receiving standard doses of NNRTIs may be being underdosed
Stephen Taylor, for HIV i-Base
Investigation into the plasma concentration effect of nevirapine (NVP) and efavirenz (EFV) was the subject of another oral presentation given by Dr Garraffo and colleagues from Nice University in France .
These investigators performed a retrospective study to try to correlate plasma drug levels with antiviral efficacy. Four hundred and forty-seven trough NNRTI concentrations (328 EFV samples and 119 NVP) were obtained over a two-year period from either drug experienced or drug naïve individuals. Drug concentrations were adjusted according to the French ANRS target values. These are 1,100-5,000ng/ml for EFV and 3,000-8,000 ng/ml for NVP.
Attempts were made to correlate drug concentrations with viral load response; the development of K103N and Y181C mutations and drug related side effects. The most startling finding was that 30% of trough levels were under the target concentration while only 2.5% were above them.
For drug naïve patients on EFV it was found that those with an undetectable viral load or the greatest viral load decrease had significantly higher plasma EFV concentrations than those with a lesser response, 1,770 ng/ml +/- 1,120 vs 1,490+/-770 p<0.05. No such difference was found in the pre treated group.
Unsurprisingly, the presence of the NNRTI mutations was significantly higher in treatment-experienced patients than naïve patients (38% vs 3 %, p<0.02). However, what was of great Interest was that a greater proportion of individuals with the K103N or Y181C mutations had plasma NNRTI concentrations below the target range.
Although these studies are subject to all of the criticisms that can be levied at retrospective analyses it remains a dramatic fact that one third of patients on the current standard of care regimens were deemed to have suboptimal NNRTI concentrations as judged by French pharmacologists. Clearly what is required is a prospective concentration controlled NNRTI study.
- Garraffo R, Lavrut T, Pierre B et al. Efavirenz and nevirapine concentration effect relationships in HIV-infected patients pharmacologically followed by routine therapeutic drug monitoring (TDM). Abs 26: P 5.1