Raltegravir dosage adjustment in HIV-infected patients receiving etravirine

Purpose. The pharmacokinetic interaction of etravirine and raltegravir is reviewed, with discussion of implications for clinical practice. Summary. Etravirine (a second-generation nonnucleoside reverse transcriptase inhibitor) and raltegravir (an integrase strand-transfer inhibitor) are two agents approved, by the Federal Food and Drug Administration for use in human immunodeficiency virus (HIV) treatment-resistant patients. Minimal data exist on the concurrent use of raltegravir with etravirine. This combination would offer treatment-experienced HIV patients a novel pharmacotherapy plan including two new fully active agents. Etravirine induces uridine diphosphate-glucuronosyltransferase 1A1 and reduces the raltegravir minimum concentration (C-min) by 34% when administered concurrently in healthy volunteers. In a case series of four HIV treatment-resistant patients initiated on an antiretroviral regimen including standard doses of etravirine and raltegravir, poor virological control was demonstrated. Two of these four patients had a raltegravir C-min below the 95% minimum inhibitory concentration. In a larger study (n = 103), sustained virological control (viral loads of <50 copies/mL) resulted when HIV treatment-resistant patients received standard doses of darunavir, ritonavir, etravirine, raltegravir, and nucleoside analogs with or without enfuvirtide. Debate exists regarding the best raltegravir pharmacokinetic parameter to evaluate (C-min or the area under the concentration curve/50% effective concentration). Recent data in HIV treatment-naive patients support a negative association between a low raltegravir C-min (<= 43 ng/mL) and virological suppression. Conclusion. The need to adjust the dosage of raltegravir in HIV-infected patients who are also receiving etravirine is unclear. In such patients who have an extensive history of HIV disease treatment, prescribing raltegravir 1200 mg/day, rather than the standard 800 mg/day, may be prudent to prevent the development of treatment-resistant virus and to achieve an optimal virological response.