Raltegravir dosage adjustment in HIV-infected patients receiving etravirine.
OBJECTIVE
The pharmacokinetic interaction of etravirine and raltegravir is reviewed, with discussion of implications for clinical practice.


CONCLUSIONS
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.


CONCLUSIONS
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.
The Johns Hopkins Hospital, Baltimore, MD, USA.
Vi T
VT
Do
Robert T
RT
Higginson
Patricia Pecora
PP
Fulco
D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D019540:Area Under Curve; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D014453:Glucuronosyltransferase / Q000187:drug effects / Q000378:metabolism; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D019428:HIV Integrase Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics; D006801:Humans; D009570:Nitriles; D011724:Pyridazines / Q000008:administration & dosage / Q000494:pharmacology*; D011743:Pyrimidines; D011760:Pyrrolidinones / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000068898:Raltegravir Potassium; D019562:Viral Load / Q000187:drug effects; D000099148:UGT1A1 Enzyme
D019380:Anti-HIV Agents; D014453:Glucuronosyltransferase; D019428:HIV Integrase Inhibitors; D009570:Nitriles; D011724:Pyridazines; D011743:Pyrimidines; D011760:Pyrrolidinones; D000068898:Raltegravir Potassium; D000099148:UGT1A1 Enzyme; C451734:etravirine