title: Efficacy and pharmacokinetics of the combination of etravirine plus raltegravir as novel dual antiretroviral maintenance regimen in HIV-infected patients.
abstract: Novel combination antiretroviral regimens may be needed for selected HIV-infected patients with toxicity or resistance. We evaluated prospectively 25 virologically suppressed patients, largely pretreated (15.6 years on therapy) with antiretroviral drug toxicity (n=19) or interactions (n=9, mainly with chemotherapy against non-Hodgkin lymphoma or anti-HCV therapy), who switched to a dual therapy with etravirine (ETR) plus raltegravir (RAL). Patients were required not to have prior virological failure or resistance to both drugs. After a median follow up of 722 days (473-1088: 53.3 patients-year), there were no cases of transient virological replication or failure. Only 1 patient left therapy at day 10 due to a grade 2 rash, and therefore efficacy by intent-to-treat analysis was 96% at 48 weeks. There were no cases of liver toxicity grade 3-4, and total cholesterol (TC) and triglycerides (TG) levels decrease significantly after initiation (TC, -17 mg/dl; p=0.01; TG, -42 mg/dl; p=0.01), as well as the TC/High density lipoprotein-cholesterol ratio (from 4.35 to 4.28). Geometric mean plasma trough level of RAL was 166 ng/ml (IQR, 40-249), well above the inhibitory concentration 90 (IC(90)). In conclusion, a novel dual therapy with ETR plus RAL is effective and well tolerated, and it could be an option to maintain durable viral suppression in hard-to-treat HIV-infected patients.
authors.affiliation: Department of Infectious Diseases, Ramón y Cajal Hospital, Madrid, Spain. Electronic address: jcasado.hrc@gmail.com.
authors.forename: José L
authors.initials: JL
authors.lastname: Casado
authors.affiliation: Department of Infectious Diseases, Ramón y Cajal Hospital, Madrid, Spain.
authors.forename: Sara
authors.initials: S
authors.lastname: Bañón
authors.affiliation: Department of Pharmacy, Ramón y Cajal Hospital, Madrid, Spain.
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Rodriguez
authors.affiliation: Department of Infectious Diseases, Ramón y Cajal Hospital, Madrid, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Moreno
authors.affiliation: Department of Infectious Diseases, Ramón y Cajal Hospital, Madrid, Spain.
authors.forename: Santiago
authors.initials: S
authors.lastname: Moreno
mesh_terms: D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects; D005260:Female; D005500:Follow-Up Studies; D006678:HIV / Q000187:drug effects / Q000502:physiology; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009570:Nitriles; D011446:Prospective Studies; D011724:Pyridazines / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology; D011743:Pyrimidines; D011760:Pyrrolidinones / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D000068898:Raltegravir Potassium; D019562:Viral Load / Q000187:drug effects
chemical_list: D019380:Anti-HIV Agents; D009570:Nitriles; D011724:Pyridazines; D011743:Pyrimidines; D011760:Pyrrolidinones; C451734:etravirine; D000068898:Raltegravir Potassium
keywords: Dual antiretroviral therapy; PI/NRTI sparing regimen; Simplification; Toxicity