EFV trials (THRIVE)] indicated RPV as non-inferior to EFV both at 48 and 96 weeks. A slightly higher incidence of virologic failures was observed with RPV (14%) vs. EFV (8%), this difference mostly

accumulated in the first 48 weeks of therapy, while failures were comparable afterwards, and occurred primarily in those with VL >100,000 c/mL. The virologic failure difference reduced in the open-label Tariquidar solubility dmso single-tablet RPV (STaR) study that used the STR formulation, suggesting the relevance of the STR on adherence [49]. In the registrative studies, the subgroups of patients with baseline HIV-RNA >100,000 copies/mL showed higher rates of virological failures and more AZD8931 cost GW3965 frequent emergence of NNRTI and NRTI resistance including the E138K resistance mutation that causes cross-resistance with etravirine (ETR) [50]. These studies have justified the approved indication limiting the use of TDF/FTC/RPV STR to patients with lower baseline

viremia. In the open-label STaR study, the TDF/FTC/RPV STR favorably compared with the TDF/FTC/EFV STR. Considering the totality of patients the second-generation STR was non-inferior to the control arm and a post hoc analysis stratified according to the baseline viral load, revealed that TDF/FTC/RPV was superior to TDF/FTC/EFV in patients with viral load <100,000 copies/mL [49]. All studies underlined the favorable tolerability profile of TDF/FTC/RPV (see Table 1) [48, 49]. RPV was well tolerated, demonstrating fewer drug discontinuations, and reduction in central nervous system (CNS) and rash AEs, when compared to EFV. These characteristics were further explored in a few small switch studies. In a cohort of patients chronically and successfully treated with TDF/FTC/EFV STR, the switch to TDF/FTC/RPV STR obtained a significant and steady reduction of CNS-related mafosfamide symptoms such as dizziness (p = 0.008), depression (p = 0.029), insomnia (p = 0.001), anxiety (p = 0.021), confusion (p = 0.005),

impaired concentration (p = 0.008), somnolence (p = 0.003), aggressive mood (p = 0.034) and abnormal dreams (p < 0.001) that turned out in a significant improvement in the quality of sleep (p < 0.001) [62]. A similar experience conducted in the US concluded that switching from TDF/FTC/EFV to TDF/FTC/RPV appears to be a safe and efficacious option in virologically suppressed HIV-1-infected subjects who experience EFV intolerance and wish to remain on a STR [63]. In a larger controlled study in experienced patients, switching to TDF/FTC/RPV was non-inferior to remaining on a PI/RTV + 2NRTIs regimen with a lower rate of virological failure in the TDF/FTC/RPV arm.