Table 4.
Influence of G-to-A hypermutation on the percentage of sequence reads containing the nucleoside and/or nucleotide reverse-transcriptase inhibitor (NRTI)–resistance mutations rtA181T, rtA194T, and rtM204I.
| Sample source, subject identifier | rtA181T
|
rtA194T
|
rtM204Ia |
||||||
|---|---|---|---|---|---|---|---|---|---|
| Prevalence
|
Prevalence
|
Prevalence
|
|||||||
| Sequence reads, no. | Total,b no. (%) | Excluded,c no. (%) | Sequence reads, no. | Total,b no. (%) | Excluded,c no. (%) | Sequence reads, no. | Total,b no. (%) | Excluded,c no. (%) | |
| NRTI-naive patients | |||||||||
| E6 | 1181 | 18 (1.5) | 12 (1.0) | 1181 | 10 (0.8) | 7 (0.6) | 3987 | 79 (2.0) | 38 (1.0) |
| 7774-0 | 2202 | 27 (1.2) | 7 (0.3) | 2195 | 31 (1.4) | 4 (0.2) | 4119 | 50 (1.2) | 17 (0.4) |
| A7 | 477 | 4 (0.8) | 2 (0.4) | 479 | 6 (1.3) | 3 (0.6) | 698 | 12 (1.7) | 9 (1.3) |
| D4 | 842 | 3 (0.4) | 1 (0.1) | 842 | 13 (1.5) | 8 (0.9) | 3108 | 27 (0.9) | 16 (0.5) |
| LSK | 331 | 2 (0.6) | 2 (0.6) | 332 | 0 (0) | 0 (0) | 1675 | 10 (0.6) | 2 (0.1) |
| C2 | 1443 | 7 (0.5) | 7 (0.5) | 1443 | 1 (0.1) | 1 (0.1) | 5448 | 6 (0.1) | 5 (0.1) |
| B5 | 1725 | 6 (0.3) | 6 (0.3) | 1719 | 9 (0.5) | 8 (0.5) | 2969 | 7 (0.2) | 5 (0.2) |
| LCS | 3197 | 8 (0.3) | 6 (0.2) | 3195 | 8 (0.3) | 4 (0.1) | 5460 | 15 (0.3) | 10 (0.2) |
| F1 | 464 | 1 (0.2) | 1 (0.2) | 464 | 0 (0) | 0 (0) | 1598 | 2 (0.1) | 2 (0.1) |
| LYC | 3129 | 3 (0.1) | 3 (0.1) | 3127 | 0 (0) | 0 (0) | 5102 | 3 (0.1) | 3 (0.1) |
| GB1 | 2837 | 4 (0.1) | 1 (0) | 2837 | 2 (0.1) | 0 (0) | 5603 | 28 (0.5) | 19 (0.3) |
| D3 | 1006 | 1 (0.1) | 1 (0.1) | 1006 | 1 (0.1) | 0 (0) | 4542 | 1 (0) | 1 (0) |
| B1 | 947 | 1 (0.1) | 1 (0.1) | 947 | 0 (0) | 0 (0) | 2939 | 3 (0.1) | 3 (0.1) |
| JS | 3048 | 2 (0.1) | 2 (0.1) | 3048 | 1 (0) | 1 (0) | 5142 | 4 (0.1) | 3 (0.1) |
| SH | 2584 | 0 (0) | 0 (0) | 2585 | 1 (0) | 1 (0) | 5379 | 7 (0.1) | 5 (0.1) |
| C7 | 3048 | 0 (0) | 0 (0) | 3050 | 0 (0) | 0 (0) | 6507 | 2 (0) | 2 (0) |
| G3 | 821 | 0 (0) | 0 (0) | 821 | 1 (0.1) | 1 (0.1) | 6492 | 3 (0) | 1 (0) |
| NRTI-treated patients | |||||||||
| 1284 | |||||||||
| 1 | 861 | 3 (0.4) | 3 (0.3) | 861 | 0 (0) | 0 (0) | NA | NA | NA |
| 2 | 3441 | 138 (4.0) | 132 (3.8) | 3440 | 13 (0.4) | 8 (0.2) | 9108 | 34 (0.4) | 26 (0.3) |
| 26278 | |||||||||
| 1 | 3276 | 49 (1.5) | 44 (1.3) | 3275 | 20 (0.6) | 10 (0.3) | NA | NA | NA |
| 2 | 3548 | 36 (1.0) | 33 (0.9) | 3548 | 11 (0.3) | 2 (0.1) | NA | NA | NA |
| 3 | 484 | 8 (1.7) | 4 (0.8) | 486 | 12 (2.5) | 2 (0.4) | NA | NA | NA |
| HTT | NA | NA | NA | 316 | 12 (3.8) | 3 (0.9) | NA | NA | NA |
| 1329 | |||||||||
| 1 | 5300 | 44 (0.8) | 43 (0.8) | 5300 | 2 (0) | 1 (0) | NA | NA | NA |
| 2 | 839 | 3 (0.4) | 0 (0) | 839 | 3 (0.4) | 2 (0.2) | NA | NA | NA |
| 7774 | |||||||||
| 1 | 3341 | 27 (0.8) | 13 (0.4) | 3341 | 16 (0.5) | 7 (0.2) | NA | NA | NA |
| 2 | 1067 | 5 (0.5) | 2 (0.2) | 1065 | 6 (0.6) | 3 (0.3) | NA | NA | NA |
| A6 | 1336 | 9 (0.7) | 2 (0.1) | 1336 | 9 (0.7) | 3 (0.2) | NA | NA | NA |
| G1 | 939 | 3 (0.3) | 1 (0.1) | 938 | 4 (0.4) | 1 (0.1) | NA | NA | NA |
| 4089 | |||||||||
| 1 | 369 | 1 (0.3) | 0 (0) | 369 | 0 (0) | 0 (0) | 2399 | 13 (0.5) | 10 (0.4) |
| 2 | 510 | 3 (0.6) | 0 (0) | 510 | 3 (0.6) | 1 (0.2) | NA | NA | NA |
| 3 | 3534 | 5 (0.1) | 1 (0) | 3547 | 7 (0.2) | 5 (0.1) | NA | NA | NA |
| CM | 910 | 0 (0) | 0 (0) | 909 | 0 (0) | 0 (0) | 2793 | 1 (0) | 1 (0) |
| 16375 | |||||||||
| 1 | 266 | 0 (0) | 0 (0) | 266 | 0 (0) | 0 (0) | 2453 | 1 (0) | 0 (0) |
| 2 | 521 | 1 (0.2) | 1 (0.2) | 522 | 0 (0) | 0 (0) | NA | NA | NA |
| 3 | 297 | 0 (0) | 0 (0) | 297 | 0 (0) | 0 (0) | NA | NA | NA |
| C5 | 1590 | 0 (0) | 0 (0) | 1590 | 1 (0.1) | 0 (0) | 8203 | 11 (0.1) | 6 (0.1) |
NOTE. G-to-A hypermutation was defined as ultra-deep pyrosequencing reads that showed >4 G-to-A changes when compared with the consensus direct polymerase chain reaction (PCR) sequence and a ratio of G-to-A changes to non–G-to-A changes >1.0. Bold type indicates prevalence ≥1.0%.
Fifteen of the 20 samples from NRTI-treated patients had M204V and/or M204I in their direct PCR sequence; therefore, only 5 samples from NRTI-treated patients were evaluated for G-to-A hypermutation at this position.
Prevalence among all sequence reads.
Prevalence when sequence reads showing G-to-A hypermutation were excluded.