TABLE 1.

Activity of FDA-approved NRTIs against HIV-1 RT with the K65R mutation^c

Compound	IC50 by single-cycle replication assaya			IC50 by multiple cycle replication assayb
	HIV-1WT	HIV-165Rd	P	HIV-1WT	HIV-165Rd	P
AZT (zidovudine)	0.20 ± 0.12	0.22 ± 0.16 (1.1)	0.77	0.031 ± 0.024	0.028 ± 0.009 (0.9)	0.58
d4T (stavudine)	5.72 ± 3.34	21.8 ± 23.8 (3.8)	<0.001	1.87 ± 0.76	3.93 ± 1.34 (2.1)	<0.05
ddC (zalcitabine)	1.35 ± 0.70	6.79 ± 3.98 (5.0)	<0.0001	0.13 ± 0.18	0.29 ± 0.23 (2.3)	0.01
ddI (didanosine)	2.32 ± 0.98	6.26 ± 2.92 (2.7)	<0.0001	0.49 ± 0.32	2.37 ± 1.80 (4.8)	<0.0001
ABC (abacavir)	6.21 ± 1.66	26.3 ± 4.18 (4.2)	<0.0001	0.076 ± 0.010	0.60 ± 0.11 (7.9)	<0.0001
3TC (lamivudine)	0.78 ± 0.48	60.5 ± 66.8 (77)	<0.0001	0.60 ± 0.46	15.3 ± 10.8 (25)	<0.0001
FTC (emtricitabine)	0.17 ± 0.07	3.75 ± 1.75 (22)	<0.0001	0.044 ± 0.036	0.90 ± 0.42 (20)	<0.001
PMPA (tenofovir)	4.67 ± 2.31	11.4 ± 3.8 (2.5)	<0.0001	0.54 ± 0.61	3.82 ± 1.91 (7.1)	<0.005
PMEA (adefovir)e	6.21 ± 0.91	23.3 ± 7.9 (3.7)	<0.001	Not tested	Not tested	Not tested

^aIC₅₀ values determined by measuring inhibition of luminescence in P4/R5 cells.

^bIC₅₀ values determined by measuring inhibition of p24 production in MT-2 cells.

^cMeans ± standard deviations from at least three independent experiments.

^dFold increase in IC₅₀ relative to wild-type results are shown in parentheses.

^eApproved for treatment of hepatitis B virus but not HIV-1.