TABLE 3.
Phenotypic and genotypic PMPA susceptibility of virus isolates obtained from SIV-infected infant macaques following short-term PMPA treatment
| Animal no. | PMPA treatment perioda | Time point (day) of virus isolateb | Phenotype IC95 (μM)c | RT codon 65d |
|---|---|---|---|---|
| 30020 | Days 5–19 | 26 | 40 | K |
| 30022 | 26 | 40 | K | |
| 30023 | 26 | 40 | K | |
| 30024 | 19 | 40 | K | |
| 30053 | Days 5–65 | 79 | 45 | K |
| 30054 | 79 | 40 | K | |
| 30055 | 79 | 40 | K | |
| 30061 | 65 | 40 | K | |
| 30074 | Days 5–65 | 65 | 45 | K |
| 30077 | NA | NA | NA |
Animals were started on short-term PMPA treatment (30 mg/kg subcutaneously once daily) 5 days after oral wild-type SIVmac251 inoculation for a total duration of 14 or 60 days.
Virus was isolated from PBMC at the end of PMPA treatment or at the first available time point after PMPA withdrawal. NA, not available (no virus could be isolated from animal 30077 during PMPA treatment or at time of euthanasia at day 65).
In vitro susceptibility to PMPA is indicated by the 95% inhibitory concentration. SIVmac mutants with K65R mutation in RT and fivefold-reduced susceptibility to PMPA, which emerged in SIVmac251-infected infant macaques following prolonged PMPA treatment, are described elsewhere (47). The IC95 of PMPA for wild-type SIVmac251 was 30 to 50 μM (with a K at RT codon 65) and the IC95 of PMPA for mutant SIVmac was 150 to 250 μM (with an R at RT codon 65).
Amino acid at codon 65 of RT. K, arginine; R, lysine.