Clonal evolution of hepatitis B virus polymerase gene mutations during lamivudine-adefovir combination treatment

Table 1 Clinical features of the chronic hepatitis B patients treated with lamivudine-adefovir sequential monotherapy followed by lamivudine-adefovir combination therapy

	Patient 1	Patient 2	Patient 3	Patient 4
Baseline characteristics
Gender	Male	Male	Male	Male
Age (yr)	39	58	51	42
Liver disease	Cirrhosis	Cirrhosis	Cirrhosis	Cirrhosis
Initial viral load (copies/mL)	3.0 × 107	3.3 × 107	7.0 × 108	5.3 × 108
HBeAg	+	+	+	+
During LMV mono-therapy
Duration of LMV (mo)	26	22	15	25
LMV-resistant mutants1	M204I + L180M	M204V	M204I + L180M	M204I + L180M
Response to LMV	VT	VT	VT	VT
During ADV mono-therapy
Duration of ADV (mo)	18	16	19	13
ADV-resistant mutants1	A181V	A181V/T	A181V	A181V
Response to ADV	NR	NR	NR	NR
During LMV-ADV combination therapy
Viral load at the start of
LMV-ADV (copies/mL)	8.0 × 107	8.0 × 107	1.2 × 105	3.1 × 106
Duration of LMV-ADV (mo)	9	13	11	15
Resistant mutants1	A181V	A181T + M204I	A181V	A181V
Response to LMV-ADV	NR	NR	NR	NR
Current treatment	LMV + ADV	LMV + TDF	LMV + TDF	LMV + TDF

¹RFMP analysis was used for the detection of resistant mutations in the hepatitis B virus polymerase gene. NR: Non-response; VT: Viral breakthrough; LMV: Lamivudine; ADV: Adefovir; TDF: Tenofovir.