TABLE 1.
Overview of maraviroc passage experiments using CCR5-tropic viruses in PM1 cells or PBL
| Virus strain (reference)a | Subtypeb | Maraviroc IC50/IC90 (nM)c | Passage experiments
|
||||||
|---|---|---|---|---|---|---|---|---|---|
| Cell type | Concn (nM) at:
|
Duration (wk) | End IC50 (nM) | FCd | End tropism | ||||
| Start | End | ||||||||
| Ba-L | B (United States) | 0.2/2.0 | PM1 | 0.04 | 80 | 32 | 0.6-1.4 | 2.6-6.6 | CCR5 |
| 0 | 0 | 32 | 0.5 | 2.3 | CCR5 | ||||
| 0.5/6.4 | PBL | 0.04 | 20 | 30 | 1.8-4.1 | 3.6-8.3 | CCR5 | ||
| 0 | 0 | 30 | 0.6 | 1.1 | CCR5 | ||||
| 92BR017 (29)e | B (Brazil) | 0.3/1.4c | PBL | 2.0 | 32 | 11 | NDg | ND | ND |
| 0 | 0 | 11 | ND | ND | ND | ||||
| 92BR018 (29)e | B (Brazil) | 0.3/1.3c | PBL | 2.0 | 64 | 20 | ND | ND | ND |
| 0 | 0 | 20 | ND | ND | ND | ||||
| 92BR023 (29) | B (Brazil) | 0.7/4.1c | PBL | 8.0 | 32 | 9 | ND | ND | ND |
| 0 | 0 | 9 | ND | ND | ND | ||||
| SF162 (1) | B (United States) | 2.3/15.2 | PBL | 16 | 8,000 | 12 | >50,000 | >21,000 | CXCR4 |
| 0 | 0 | 12 | >50,000 | >21,000 | CXCR4 | ||||
| CC1/85 (3)f | B (United States) | 3.0/12.2 | PBL | 2 | 4,000 | 16 | >5,600 | >1,526 | CCR5 |
| 0 | 0 | 16 | 1.9 | 0.65 | CCR5 | ||||
| RU570 | G (Russia) | 2.5/149 | PBL | 32 | 16,000 | 18 | >50,000 | >20,000 | CCR5 |
| 0 | 0 | 18 | 0.59 | 0.24 | CCR5 | ||||
All isolates were obtained from the Centralized Facility for AIDS Reagents (NIBSC, Potters Bar, United Kingdom), except for CC1/85 (kindly provided by John Moore). Isolates were chosen for inclusion on the basis of a relatively high maraviroc IC90 as determined by Dorr et al. (6) (unless otherwise specified).
Subtype and starting coreceptor usage were assigned by NIBSC.
The IC50 and IC90 quoted for Brazilian isolates were determined as described by Dorr et al. (6) and are means of four to eight determinations. For other isolates, the values quoted were determined in drug susceptibility assays where the start and passaged viruses were tested in parallel. In most cases, these values were in good agreement with those determined by Dorr et al. (6); the IC90 for the RU570 isolate was 5- to 10-fold higher than previously reported, but a complete dose-response curve was obtained.
FC, fold change in IC50 relative to the prepassage virus tested in parallel.
Chosen on the basis of good growth in PBL in vitro.
Chosen on the basis of prior use to generate escape mutants to other CCR5 antagonists (14, 18, 27).
ND, not done.