Table 2.

Guideline-Suggested Approaches to Re-treatment of Complex DAA Failures

	AASLD/IDSA [17]	EASL [16]a
Initial NS5A failureb	a. SOF/VEL/VOX for 12 wkc or b. SOF + GLE/PIB + RBV for 16 wkd	a. SOF/VEL/VOX for 12 wk or b. SOF + GLE/PIB + RBV for 12 wke
SOF/VEL/VOX failure or otherwise particularly difficult to curef	a. SOF + GLE/PIB + RBV for 16 wk or b. SOF/VEL/VOX + RBV 24 wk	a. SOF/VEL/VOX + RBV for 12–24 wk or b. SOF + GLE/PIB + RBV for 12–24 wk

Abbreviations: AASLD, American Association for the Study of Liver Diseases; DAA, direct-acting antiviral; EASL, European Association for the Study of the Liver; GLE, glecaprevir; IDSA, Infectious Diseases Society of America; NS5A, nonstructural protein 5A; PIB, pibrentasvir; RAS, resistance-associated substitution; RBV, ribavirin; SOF, sofosbuvir; VEL, velpatasvir; VOX, voxilaprevir.

^aResistance testing recommended (if available) before treatment.

^bGLE/PIB for 16 weeks is an alternative for NS5A treatment failure without NS3 PI exposure.

^cRBV is recommended for genotype 3 with cirrhosis or GLE/PIB failures with cirrhosis.

^dRecommended specifically in the setting of initial GLE/PIB failure.

^ePreferred in setting of complex RAS profile or cirrhosis with other negative predictors.

^f“Particularly difficult-to-cure” not strictly defined; may include multiple NS5A regimen failures and GLE/PIB failure in the setting of cirrhosis with other negative predictors (eg, complex RAS profiles).