Table 1. Susceptibility of HIV-1 isolates to RAL and distinct differences in IN region sequences between RAL-selected and control-passaged viruses.
Isolate | Subtype | Tropism | Passage no. | Concn (nM) | RAL-selected variant* | Passage control | ||
IN sequence | RAL IC50 (nM) | IN sequence | RAL IC50 (nM) | |||||
KP-1 | B | Mix | 0 | 0 | K/R7, K/R111, Q/H216, D/N278 | 4 | K/R7, K/R111, Q/H216, D/N278 | 4 |
8 | 20 | K111, H216, D278 | 31 (7.8) | R7, R111, Q216, N278 | 4.5 (1.2) | |||
17† | 20 | K7, K111, H216, D278 | 26 (6.5) | R7, R111, Q216, N278 | 0.4 (0.1) | |||
KP-2 | CRF08_BC | R5 | 0 | 0 | I201, ins289NQDME | 16 | I201, ins289NQDME | 16 |
18 | 40 | G189G/R, I201, ins289NQDME | 32 (2) | I201, ins289NQDME | 16 (1) | |||
30 | 85 | G189R, I201, ins289NQDME | 55 (3.4) | I201, ins289NQDME | 25 (1.6) | |||
KP-3 | B | R5 | 0 | 0 | V72, A125 | 32 | V72, A125 | 32 |
11 | 25 | V72, A125 | 25 (0.78) | V72, A125 | 33 (1) | |||
22 | 27.5 | V72, A125 | 37 (1.2) | V72, A125T | 13 (0.41) | |||
KP-4 | CRF01_AE | X4 | 0 | 0 | – | 2.1 | – | 2.1 |
8 | 40 | – | 33 (16) | R166R/K, D279N | 4.4 (2.1) | |||
29 | 40 | T210I | 22 (10) | G163E, R166R/K, D279N/S | 4.1 (2) | |||
89.6 | B | R5X4 | 0 | 0 | – | 1.2 | – | 1.2 |
8 | 15 | – | 34 (28) | – | 4.4 (3.7) | |||
34 | 20 | – | 11 (9.2) | V180I | 1.2 (1) |
Amino acid changes in each passage variant are shown. Italicized letters represent mutations relative to the consensus subtype BC or B present in the baseline isolates. Bold letters represent amino acids selected out of the quasi-species cloud. The fold increase in RAL IC50 values is shown in parentheses for in vitro-selected variants compared with those in the baseline isolates.
The RAL variant selected after 17 passages was compared with the control selected after 20 passages.