Opass Putcharoen, Stephen J Kerr, Kiat Ruxrungtham

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.