Does Once-Daily Etravirine Have a Role in the Management of HIV-1 Infection?

Abstract

When individualizing therapy for HIV-positive patients and for those in whom the 'preferred regimens' of the US Department of Health and Human Services HIV treatment guidelines are not appropriate, a once-daily non-nucleoside with a fixed-dose combination of two nucleosides may be considered in patients who are adherence challenged, intolerant to other regimens but with no viral resistance, or in those in whom the pill burden or actual pill size was too great to accept. Despite having a 30- to 40-h elimination half-life, etravirine was never considered for once-daily dosing during development due to an unacceptably high pill burden in phase II trials. However, a recently published study, SENSE, enrolled 157 HIV-positive patients in a multinational, randomized, placebo-controlled, double-blind trial that investigated 400 mg etravirine once daily with two nucleosides versus a comparator arm that included efavirenz and two nucleosides. The primary objective was to assess neuropsychiatric tolerability over the 48-week study period, with comparative efficacy as a secondary objective. Using the intent-to-treat time to loss of virologic response (ITT-TLOVR) analysis at 48 weeks, 76 % of patients receiving etravirine had an undetectable viral load of <50 copies/mL compared with 74 % of patients receiving efavirenz. This translates to a suppression rate difference of 1.6 % favouring etravirine (95 % CI -12.0-15.2) and met the non-inferiority criteria of a delta of -12 %. Baseline viral load was not observed to impact clinical response rates. Pharmacokinetically and clinically, studies indicate the efficacy and safety of utilizing once-daily etravirine in the treatment-naive population. While it is not appropriate for all patients, once-daily etravirine is best utilized for patients in whom caloric requirements, pill burden, pill size, potential adverse reactions, concomitant medications/drug interactions, psychosocial factors and patient preference preclude the use of a 'preferred' regimen. Etravirine dissolution in water allows for the flexibility of once-daily dosing with one fixed-dose combination tablet followed by an etravirine/water 'chaser'.