Can low NVP plasma concentrations explain the results seen in the EFV and NVP containing arms of the NARVAL study?

Giles Peytavin of the Bichat Claude Bernard Hospital in Paris presented data that evaluated this issue [1]. In the Narval trial – a study including drug experienced but NNRTI naïve individuals – the multivariate analysis looking at predictors of virological success at week 12, suggested that the use of EFV rather than NVP was significantly associated with a better virological outcome. In this presentation the investigators postulated that suboptimal NNRTI concentrations could partially account for this finding.

Of the 541 patients, 42% and 24% received either EFV 600mg QD or NVP 200mg BD respectively as part of their new regimen. Virological success was defined as VL < 200copies/mL at week 12. EFV concentrations were considered adequate if they were above 1,100 ng/mL for EFV or above 4,000 ng/mL for NVP. Plasma concentrations of NVP and EFV were measured at weeks two, six and 12.

Reporting the results of the study, 56% and 28% of patients treated with EFV or NVP respectively had a VL < 200 copies/mL at week 12. The median plasma EFV concentrations were 2,400 ng/mL (10-14,300, n=288). EFV plasma concentrations were considered adequate in 90% of patients using this agent. In contrast the median plasma NVP concentrations were 4,500 ng/mL (50-29,000; n= 166) and were considered adequate in only 54% (p<0.0001) of patients. The authors speculated that these findings could explain why EFV and not NVP was associated with virological success in the multivariate analysis. They then went on to suggest that the usefulness of TDM in these HAART experienced but NVP naïve patients may be to “dose increase” a proportion of patients who may benefit from higher drug concentrations, considering that over 50% of this cohort were deemed to have sub optimal NVP concentrations.