Challenge to overcome: Nonstructural protein 5A-P32 deletion in direct-acting antiviral-based therapy for hepatitis C virus

Table 1 Characteristics of P32 deletion

Characteristic	Description
Position	Nonstructural protein 5A
Frequency in patients who experienced DCV/ASV failure	< 10% (4.3% to 9.5%)
Extent of resistance in the HCV GT1b Con1 replicon	> 1000-fold resistance to PIB and > 10000-fold resistance to DCV, LDV, VEL, EBR, or OBV
Extent of resistance in the infectious culture systems	> 1000-fold resistance to PIB, DCV, LDV, VEL, EBR, OBV, or RZR
Prior DAA therapy to develop P32del	DCV/ASV or SOF/LDV
RAS that is unlikely to be coexistent with	Y93H
Therapy that is unlikely to be effective	GLE/PIB or SOF/LDV
Therapy that is expected to be effective	"GLE/PIB plus SOF" or "SOF/LDV plus RBV"
Therapy that might to be effective	"SOF/VEL plus VOX" or "SOF/VEL"

ASV: Asunaprevir; DAA: Direct-acting antiviral; DCV: Daclatasvir; EBR: Elbasvir; GLE: Glecaprevir: GT: Genotype; HCV: Hepatitis C virus; LDV: Ledipasvir; OBV: Ombitasvir; P32del: P32 deletion; PIB: Pibrentasvir; RAS: Resistance-associated substitution; RBV: Ribavirin; RZR: Ruzasvir; SOF: Sofosbuvir; VEL: Velpatasvir; VOX: Voxilaprevir.