In ART-experienced patients who are virologically suppressed with an undetectable plasma HIV RNA level

(<50 copies/mL), the risk of hypersensitivity and/or hepatotoxicity on switching INCB018424 concentration to NVP is not increased in patients with higher CD4 cell counts (above the gender-specific CD4 cell count thresholds) [59]. In ART-experienced patients with detectable plasma HIV RNA levels, a switch to NVP is not advised. Furthermore, the need to minimize any window for developing resistance is greatest in patients who discontinue EFV early on when virological suppression has not yet been achieved. The latter scenario is made more complex when enzyme induction has not yet been fully achieved, and if doubt exists, alternatives to switch to should be considered. Steady-state (14 days following the

switch) ETV pharmacokinetic parameters are lowered by previous EFV intake in the case of both once-daily (Cmin was lowered by 33%) and twice-daily (Cmin was lowered by 37%) administration. However, ETV concentrations have been shown to increase over time following the switch and in patients with undetectable VLs switching from EFV to ETV, standard doses of ETV can be commenced [60]. To date, no data are available Selleck Ribociclib on what strategy to adopt in patients with active viral replication. Concentrations of RPV are lowered by previous EFV administration. However, 28 days after the switch, they returned to levels comparable with those when RPV was administered without previous EFV treatment, Cepharanthine except for a 25% lower Cmin.

Therefore, in patients with undetectable VLs switching from EFV to RPV, standard doses of RPV can be commenced [61]. To date, no data are available on what strategy to adopt in patients with active viral replication. Because of the strong inhibitory effect of ritonavir on CYP450 3A4, it is unlikely to require a modification of the PI/r dose when switching from EFV to PI/r. Formal pharmacokinetic data are unavailable. TDM data were presented on ATV/r and showed that after stopping EFV, ATV concentrations were above the suggested minimum effective concentration in all studied subjects [62]. Although formal pharmacokinetic data are not available, switching EFV to RAL should not lead to clinically significant consequences, as co-administration of EFV with RAL led to a moderate-to-weak reduction in RAL Cmin (21%) [63], which may persist for 2–4 weeks, after the switch but the degree of this reduction is unlikely to be clinically meaningful. A formal pharmacokinetic study in HIV-positive individuals showed that the induction effect of EFV necessitated an increase in MVC dose to 600 mg twice daily for 1 week following the switch [64]. MVC 300 mg twice daily (standard dose) seems to be safe after this period.