Non-
nucleoside analog reverse transcriptase inhibitors (NNRTIs) are an important component of combination antiretroviral regimens. Amongst the NNRTIs,
efavirenz is commonly recommended for initial regimens in treatment-naïve HIV patients, but its use in some settings is limited by adverse effects, particularly those affecting the central nervous system and lipid metabolism.
Rilpivirine is a new second-generation NNRTI that is recommended as an alternative to
efavirenz in treatment-naïve HIV patients. Evidence of the clinical efficacy of
rilpivirine versus
efavirenz, in combination with two
nucleoside or
nucleotide analog
reverse transcriptase inhibitors in treatment-naïve patients, is derived from the THRIVE and ECHO studies. These studies demonstrated that
rilpivirine 25 mg once daily was potent and noninferior to
efavirenz 600 mg once daily using an intention-to-treat time-to-loss-of-virologic-response (ITT-TLOVR) endpoint. Although virologic failure was higher in subjects treated with
rilpivirine, study discontinuations due to adverse effects were more common in subjects treated with
efavirenz. In addition, the virologic response to
rilpivirine was suboptimal in patients with a baseline viral load >100,000 copies/mL. The overall incidence of adverse events and grade 2-4 adverse events was lower in the
rilpivirine than in the
efavirenz groups. Patients with
rilpivirine failure were more likely to have resistance mutations that confer cross-resistance to other NNRTIs, including
etravirine.
Rilpivirine is currently available as a fixed-dose combination that allows for once-daily administration as a single pill, and is approved for use in treatment-naïve patients. This
drug is contraindicated when co-administered with
rifamycins or
proton-pump inhibitors.