Efficacy and pharmacokinetics of the combination of etravirine plus raltegravir as novel dual antiretroviral maintenance regimen in HIV-infected patients

• Novel antiretroviral strategies are needed in selected HIV infected patients, mainly due to toxicity.
• We evaluate a novel dual regimen, etravirine plus raltegravir, in patients with intolerance or drug interactions.
• The efficacy was 96% at 48 weeks, there were no adverse events, and lipid parameters improved during follow up.
• A pharmacokinetic evaluation showed no significant interactions between both drugs.
• Etravirine plus raltegravir seems a useful option for hard-to-treat HIV-infected patients.

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 (IC90). 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.