Raltegravir trough levels reduced by etravirine may require use of TDM
Several pharmoacokinetic studies have reported a negative impact on raltegravir trough concentrations when used in combinations that include etravrine. A letter published in the 27 April 2009 issue of the publication AIDS, from Amelie Menard and colleagues, detailed four cases where significant reductions in trough levels of raltegravir were identified in patients who added or included etravirine in their antiretroviral combination. 
These cases suggest that TDM should be used for patients using both drugs together and that the significance of the interaction may be clinically important in some patients.
The Liverpool HIV drug interaction group  summarised these cases:
The first case had raltegravir trough concentrations of 189 and 313 ng/ml on two occasions whilst on darunavir/ritonavir, enfuvirtide and raltegravir. After switching enfuvirtide for etravirine, raltegravir trough concentrations decreased to 10 ng/ml and then to 5 ng/ml one month later. The second case started a combination of tenofovir/emtricitabine, etravirine and raltegravir. Tenofovir trough concentrations were in the expected range, but raltegravir trough concentrations were considered low (30 ng/ml). Increasing raltegravir from 800 mg/day to 1200 mg/day resulted in an increase in trough concentration (67 ng/ml). The third case had low raltegravir trough concentrations on two occasions (12 and 9 ng/ml) whilst receiving darunavir/ritonavir, etravirine and raltegravir. The final case switched to tenofovir, etravirine and raltegravir. Etravirine trough concentrations were within the normal range, but raltegravir trough concentrations were low (29 ng/ml).
In all these cases, raltegravir concentrations were below the mean trough concentration previously observed in initial clinical trials (63 ng/ml, range 29-118 ng/ml. 
In two of the cases, concentrations were below the in vitro IC95 for raltegravir of 14.6 ng/ml.
An interaction study in healthy volunteers showed that coadministration of raltegravir and etravirine decreased raltegravir trough concentrations by 34%, with minimal effect on AUC and Cmax (~10% decrease). In this study the authors concluded that no dose adjustment for either drug was necessary. 
However, given the wide inter-individual variability in the pharmacokinetics of raltegravir and these reports from HIV-positive subjects, a more cautious approach may be required.
- Menard A et al. Etravirine-raltegravir, a marked interaction in HIV-1-infected patients:: about four cases. Correspondence, AIDS 27 April 2009, Volume 27 Issue 7, p 869-871. doi:: 10.1097/QAD.0b013e328329915f
- News and archive, May 2009.
- Markowitz M et al. Antiretroviral activity, pharmacokinetics, and tolerability of MK-0518, a novel inhibitor of HIV-1 integrase, dosed as monotherapy for 10 days in treatment-naive HIV-1-infected individuals. J Acquir Immune Defic Syndr. 2006 Dec 15;43(5):509-15.
- Anderson MS et al, Minimal pharmacokinetic interaction between the human immunodeficiency virus nonnucleoside reverse transcriptase inhibitor etravirine and the integrase inhibitor raltegravir in healthy subjects. Antimicrob Agents Chemother. 2008 Dec;52(12):4228-32. Epub 2008 Oct 6.