Table 3. Anti-HIV-1 activity of nucleoside analogues in SAMHD1 expressing U937 cells.
Nucleoside analogue | PMA− |
PMA+ |
||||||
---|---|---|---|---|---|---|---|---|
EC50 (μM)a [95% CI]b |
Fold | pc | EC50 (μM) [95% CI] |
Fold | p | |||
SAMHD1 | HD206/7AA | SAMHD1 | HD206/7AA | |||||
ACV | >200 | >200 | — | — | 0.652 [0.175–1.13] | 50.9 [46.1–55.8] | 78 | <0.0001 |
GCV | >200 | >200 | — | — | 0.876 [0.823–0.929] | >200 | >228 | <0.0001 |
CFB | 0.138 [0.021–0.255] | 0.108 [0.081–0.135] | 1 | 0.0878† | 0.0013 [0.000–0.002] | 0.029 [0.022–0.036] | 22 | 0.0010 |
d4T | 0.801 [0.531–1.07] | 2.71 [1.90–3.52] | 3 | 0.0013 | 0.528 [0.317–0.739] | 5.82 [5.671–5.969] | 11 | <0.0001 |
ddI | 23.7 [10.6–36.7] | 55.1 [44.2–65.9] | 2 | 0.0018 | 0.109 [0.030–0.188] | 8.79 [7.53–10.1] | 81 | <0.0001 |
ABC | 17.5 [15.9–19.1] | 22.1 [7.12–37.1] | 1 | 0.0590† | 0.173 [0.164–0.182] | 7.06 [4.72–9.40] | 41 | <0.0007 |
NVP | 0.112 [0.000–0.223] | 0.124 [0.000–0.248] | 1 | 0.6442† | 0.097 [0.000–0.195] | 0.145 [0.113–0.177] | 1 | 0.1297† |
RAL | 0.011 [0.002–0.020] | 0.012 [0.003–0.021] | 1 | 0.2115† | 0.070 [0.013–0.127] | 0.075 [0.007–0.143] | 1 | 0.7548† |
aEC50 is the effective concentration of drug that inhibits infection of cells by 50% measured as the percentage of GFP+ cells in SAMHD1+ or HD206/7AA+ populations. Values were calculated by non-linear regression for at least two independent experiments.
b95% confidence interval. Non-ambiguous values were subject to a replicate test.
cEC50 values for each replicate were used to perform an unpaired two-tailed t-test to determine differences between SAMHD1+ and HD206/7AA+ populations.
†Difference not statistically significant.