TABLE 1.
Antiviral potency and toxicity of ruxolitinib and tofacitinib in primary human lymphocytes and macrophagesa
| Compound | Anti-HIV-1 activity in hPBMC (μM) |
Anti-HIV-2 activity in hPBMC (μM) |
Anti- RT-SHIV activity in mPBMC (μM) |
Anti-HIV-1 activity in human Mϕ (μM) |
Anti-RT-SHIV activity in macaque Mϕ (μM) |
IC50 (μM) in hPBMC with: |
IC50 in human Mϕ (μM) | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| EC50 | EC90 | EC50 | EC90 | EC50 | EC90 | EC50 | EC90 | EC50 | EC90 | PHA+IL-2 | PHA | ||
| Ruxolitinib | 0.1 ± 0.02 (>100) | 4.7 ± 0.07 (11) | 0.02 ± 0.01 (>100) | 0.4 ± 0.2 (>100) | 0.09 ± 0.1 (>100) | 1.3 ± 0.8 (38) | 0.3 ± 0.1 (>100) | 3.1 ± 1.8 (48) | 0.4 ± 0.2 (>100) | 4.2 ± 1.3 (12) | >50 | >50 | >100 |
| Tofacitinib | 0.8 ± 0.3 (62) | 17.1 ± 15.1 (3) | 0.07 ± 0.006 (>100) | 1.8 ± 1.1 (28) | 0.3 ± 0.1 (>100) | 2.9 ± 0.5 (17) | 0.2 ± 0.08 (>100) | 2.9 ± 1.4 (17) | 0.3 ± 0.2 (>100) | 3.1 ± 0.9 (16) | >50 | >50 | 49.2 |
| AZT | 0.02 ± 0.008 (>100) | 0.13 ± 0.03 (>100) | 0.001 ± 0.0008 (>100) | 0.01 ± 0.01 (>100) | 0.002 ± 0.001 (>100) | 0.03 ± 0.02 (>100) | 0.01 ± 0.02 (>100) | 0.07 ± 0.12 (>100) | 0.08 ± 0.1 (>100) | 0.9 ± 0.7 (>100) | >50 | >50 | >100 |
a
Activity was determined in acutely infected cells. Data are means and standard deviations calculated from at least four independent experiments, with pooled cells from eight donors and duplicates in each experiment. Parentheses indicate therapeutic index (ratio of toxicity to potency). hPBMC, human peripheral blood mononuclear cells; mPBMC, macaque peripheral blood mononuclear cells; Mϕ, macrophages.