Table 3.
Potency of RDV with concomitant medications commonly used in SUDV- and MARV-endemic regions tested in in vitro assays.
| Category 1: Drugs with no innate activity against SUVD or MARV when tested in combination with RDV | |||||
|---|---|---|---|---|---|
| Drug of interest (tested at fixed concentration1) | RDV activity against SUDV when in combination | RDV activity against MARV when combination | Drug-drug interaction? (RDV potency) | ||
| EC502 (µM) | CC50 (µM) | EC50 (µM) | CC50 (µM) | ||
| RDV alone | 0.308 ± 0.313 (n = 9; 0.089, 0.936) | > 2.5 | 0.109 ± 0.054 (n = 9; 0.037, 0.189) | > 2.5 | |
| Acetaminophen (75 μM) | 0.50 ± 0.56 | > 2.5 | 0.13 ± 0.02 | > 2.5 | No |
| Amodiaquine (0.07 μM) | 0.052 ± 0.044 | > 2.5 | 0.33 ± 0.10 | > 2.5 | Enhanced5 for SUDV |
| Artemether (0.7 μM) | 0.48 ± 0.55 | > 2.5 | 0.13 ± 0.03 | > 2.5 | No |
| Artesunate (1.2 µM) | 0.31 ± 0.45 | > 2.5 | 0.15 ± 0.03 | > 2.5 | No |
| Artesunate (8.5 µM) | < 0.02 (tox3) | < 0.2 | 0.16 ± 0.06 | > 2.5 | |
| Atovaquone (3.7 µM) | 0.094 ± 0.067 | > 2.5 | 0.08 ± 0.02 | > 2.5 | No |
| Atovaquone (22.6 µM) | < 0.02 (tox3) | < 0.02 | 0.016 ± 0.006 | < 0.02 | |
| Ciprofloxacin (14 µM) | 0.041 ± 0.002 | > 2.5 | 0.14 ± 0.03 | > 2.5 | Enhanced for SUDV |
| Diazepam (1.7 µM) | 0.50 ± 0.49 | > 2.5 | 0.11 ± 0.04 | > 2.5 | No |
| Metronidazole (30 µM) | 0.42 ± 0.46 | > 2.5 | 0.103 ± 0.005 | > 2.5 | No |
| Omeprazole (3.2 µM4) | 0.22 ± 0.19 | > 2.5 | 0.15 ± 0.07 | > 2.5 | No |
| Ondansetron (0.3 µM) | 0.40 ± 0.33 | > 2.5 | 0.12 ± 0.03 | > 2.5 | No |
| Proguanil (3.2 µM) | 0.57 ± 0.59 | > 2.5 | 0.16 ± 0.05 | > 2.5 | No |
| Lamivudine (11.3 µM) | 0.67 ± 0.75 | > 2.5 | 0.14 ± 0.06 | > 2.5 | No |
| Lopinavir (15.6 µM) | See data below | See data below | 0.29 ± 0.20 | > 2.5 | No for MARV |
| Ritonavir (1.8 µM) | 0.35 ± 0.34 | > 2.5 | 0.15 ± 0.05 | > 2.5 | No |
| Tenofovir disoproxil fumarate (0.5 µM) | 0.10 ± 0.04 | > 2.5 | 0.09 ± 0.03 | > 2.5 | No |
| Category 2: Drugs with innate activity against SUDV or MARV when tested alone | |||||
|---|---|---|---|---|---|
| Drug of interest | Activity against SUDV | Activity against MARV | |||
| EC50 (µM) | CC50 (µM) | EC50 (µM) | CC50 (µM) | ||
| Efavirenz | 2.24 ± 0.57 | 20.7 ± 10.1 | 19.8 ± 0.1 | 15.1 ± 4.1 | |
| Lopinavir | 2.32 ± 0.58 | 34.1 ± 0.9 | > 100 | > 100 | |
| Lumefantrine | 9.60 ± 0.52 | 40.0 ± 1.2 | 16.6 ± 7.3 | 37.3 ± 0.9 | |
| Ceftriaxone | 2.24 ± 0.57 | 20.9 ± 10.1 | 19.8 ± 0.1 | 15.1 ± 4.1 | |
| Drugs from Category 2 against SUDV or MARV when tested in combination with RDV | |||||
|---|---|---|---|---|---|
| Drug of interest (tested at fixed concentration1) | RDV activity against SUDV when in combination | RDV activity against MARV when combination | Drug-drug interaction? (RDV potency) | ||
| EC502 (µM) | CC50 (µM) | EC50 (µM) | CC50 (µM) | ||
| Efavirenz (5 µM) | < 0.015 | > 2.5 | 0.13 ± 0.13 | > 2.5 | Not antagonistic |
| Efavirenz (11 µM) | ND | ND | 0.075 ± 0.042 | > 2.5 | |
| Efavirenz (41 µM) | < 0.02 | < 0.02 | < 0.02 | < 0.02 | |
| Lopinavir (15.6 µM) | < 0.02 | > 2.5 | 0.29 ± 0.20 | > 2.5 | Not antagonistic |
| Lumefantrine (12 µM) | 0.026 ± 0.021 | > 2.5 | 0.103 ± 0.005 | > 2.5 | Not antagonistic |
| Ceftriaxone (440 µM) | < 0.017 | > 2.5 | 0.078 ± 0.011 | > 2.5 | Not antagonistic |
Compounds are divided into two categories based on whether they have antiviral effects against SUDV or MARV as a single agent.
ND not determined.
1Concentration equivalent to human plasma Cmax and has not been adjusted with protein-binding. Lower concentrations were used when significant cell killing was observed.
2EC50 values represent averages from 2–3 independent experiments.
3The observed antiviral effect is driven by cytotoxicity.
4Tested at concentration ~ 19-fold over reported Cmax (unadjusted for protein-binding).
5Enhanced activity is defined by > fivefold increase of antiviral activity of the combination over the RDV-alone treatment.