Table 2.

Inhibition of steady-state WT and mutant HIV-1 RT DNA synthesis by 6-modified-3′-azido-ddGTP analogs

Nucleotide analog	HIV-1 RT
	WT	K65R	L74V	M184V	Q151Ma
ZDV-TP
IC50 (µM)b	0.13 ± 0.04	0.66 ± 0.20	0.18 ± 0.10	0.12 ± 0.03	2.7 ± 1.0
Fold-Rc	–	5.2	1.4	0.9	21.0
3′-azido-ddGTP
IC50 (µM)	0.15 ± 0.01	0.36 ± 0.02	0.25 ± 0.10	0.06 ± 0.02	0.30 ± 0.20
Fold-R	–	2.5	1.7	0.4	2.1
3′-azido-ddATP
IC50 (µM)	0.16 ± 0.10	0.70 ± 0.10	0.42 ± 0.10	0.19 ± 0.10	1.44 ± 1.00
Fold-R	–	4.3	2.5	1.2	8.8
3′-azido-2,6-DA-P-TP
IC50 (µM)	0.80 ± 0.10	2.5 ± 1.6	1.3 ± 0.4	0.34 ± 0.10	4.2 ± 3.6
Fold-R	–	3.1	1.6	0.4	5.3
P-valued	–	0.36	0.08	0.02	0.45
3′-azido-6-Cl-P-TP
IC50 (µM)	3.2 ± 0.8	9.1 ± 3.8	11.8 ± 3.9	2.5 ± 1.0	30.8 ± 6.1
Fold-R	–	2.9	3.7	0.8	9.7
P-value	–	0.12	0.15	0.22	0.81
3′-azido-6-AA-P-TP
IC50 (µM)	4.10 ± 0.8	8.8 ± 0.8	10.3 ± 1.9	4.8 ± 0.6	21.8 ± 12.0
Fold-R	–	2.2	2.5	1.2	5.3
P-value	–	0.0006	0.97	0.94	0.43
3′-azido-6-DM-P-TP
IC50 (µM)	23.4 ± 13.0	>50	>50	N.D.e	>50
Fold-R	–	>2.0	>2.0		>2.0
P-value	–	–	–	–	–
3′-azido-6-MX-P-TP
IC50 (µM)	24.4 ± 7.0	80.1 ± 6.1	>100	32.9 ± 23.0	78.0 ± 34.0
Fold-R	–	3.3	>4.0	1.3	3.2
P-value	–	0.10	–	0.71	0.31

^aThe Q151M RT contained the A62V, V75I, F77L, F116Y and Q151M mutations.

^bIC₅₀ values are the concentration of drug required to inhibit 50% of DNA synthesis under steady-state assay conditions.

Data are shown as the mean ± standard deviation of at least three independent experiments.

^cFold-resistance (Fold-R) values are calculated by IC₅₀^{mutant RT}/IC₅₀^{WT RT}.

^dP-value compares the Fold-R values determined for the 6-modified 3′-azido-ddGTP analogs to the Fold-R value determined for 3′-azido-ddATP.

^eNot determined.