Table 2. Effects of etravirine on HIV-1 reverse transcriptase, recovered from plasma of HIV-1 infected patients.
Mutations at amino acid | Antiviral score according to | |||||||||||||||
Patient/Sample | Fold difference in ETR IC50 | 90 V | 98 A | 100 L | 101 K | 103 K | 106 V | 108 V | 138 E | 179 V | 181 Y | 190 G | 238 K | Stanford | Tibotec | Monogram |
BH10* | 1.0 | NA | NA | NA | ||||||||||||
L100I* | 12.0 | 15 (i) | 2.5 (i) | 4 (r) | ||||||||||||
1 | 11.8 | S | A | 0 (s) | 0 (s) | 2 (s) | ||||||||||
2 | >100 | N | Q | T | 10 (s) | 1 (s) | 2 (s) | |||||||||
3a | 4.5 | S | D | 10 (s) | 1 (s) | 1 (s) | ||||||||||
3b | >100 | I | S | D | C | 45 (i) | 4.5 (r) | 6 (r) | ||||||||
4 | 3.9 | R | 0 (s) | 0 (s) | 1 (s) | |||||||||||
5a | 45.8 | I/R | G | 0 (s) | 0 (s) | 0 (s) | ||||||||||
5b | 71.4 | I/R | G | 0 (s) | 0 (s) | 0 (s) | ||||||||||
6 | >100 | I | I | N | 20 (i) | 3.5 (i) | 5 (r) | |||||||||
7 | 0.7 | 0 (s) | 0 (s) | 0 (s) | ||||||||||||
8a | >100 | N | C | 30 (i) | 2.5 (i) | 4 (r) | ||||||||||
8b | >100 | N | C | 30 (i) | 2.5 (i) | 4 (r) | ||||||||||
9a | 4.6 | S | N | I | T | 0 (s) | 0 (s) | 1 (s) | ||||||||
9b | 9.2 | S | N | I | T | 0 (s) | 0 (s) | 1 (s) | ||||||||
10 | 13.6 | N | I | 0 (s) | 0 (s) | 0 (s) | ||||||||||
11a | 7.3 | N | I | 0 (s) | 0 (s) | 1 (s) | ||||||||||
11b | 4.1 | I | 0 (s) | 0 (s) | 1 (s) | |||||||||||
12 | 2.0 | N | 0 (s) | 0 (s) | 0 (s) | |||||||||||
13 | 68.8 | N | A | 10 (s) | 1 (s) | 1 (s) | ||||||||||
14 | 29.1 | S | N | A | 5 (s) | 1.5 (s) | 3 (s) | |||||||||
15 | 2.9 | N | 0 (s) | 0 (s) | 0 (s) | |||||||||||
16 | 1.7 | N | 0 (s) | 0 (s) | 0 (s) | |||||||||||
17 | 2.9 | N | 0 (s) | 0 (s) | 0 (s) | |||||||||||
18 | 4.1 | I | N | 0 (s) | 1 (s) | 1 (s) | ||||||||||
19 | 6.4 | N | 0 (s) | 0 (s) | 0 (s) | |||||||||||
20 | 7.2 | N | 0 (s) | 0 (s) | 0 (s) |
*Two recombinant reverse transcriptase, (BH10)-wild-type (WT) and its mutant form L100I, were used as references. Based on the IC50 value of BH10-wild-type (1.0±0.18 µM), which was included in every run, the IC50 value and the fold-difference in susceptibility of each isolate were determined. A fold-difference of <5 was considered as sensitive, between 5–15 as decreased susceptibility, and above 15 as resistant.
Abbreviations: NA, not applicable; IC50, inhibitory effect; ETR etravirine.
**Genotype result was obtained six months earlier. The results of three genotypic scoring systems (Stanford, Monogram Weighted Score, Tibotec Weighted Genotype Score) predicting ETR susceptibility are presented. s: sensitive; i: intermediate; r: resistant. A Stanford score of 0-<15, ≥15-<60 and ≥60 are defined as susceptible, intermediate and resistant. Tibotec weighted genotypic score of 0–2, 2.5–3.5 and ≥4 are predictive of susceptible, intermediate and reduced response. Monogram defines a weighted score of 0–3 as susceptible and ≥4 as resistant.