TABLE 5.
NNRTI resistance mutations and estimated NNRTI resistance levels for sequences with differences in genotypic resistance testing results by Sanger sequencing and NGS
| Sample group and sample identifier | DRM detected by: |
Sanger sequencing score → NGS scorea |
||||
|---|---|---|---|---|---|---|
| Sanger sequencing and NGS | Sanger sequencing alone | NGS alone | EFV | ETR | RPV | |
| Samples for which NGS reported higher levels of resistance to ≥1 NNRTIs | ||||||
| B2-16 | 103N | 1 → 5 | 1 | 1 | ||
| B2-35 | 138A | 103N | 1 → 5 | 2 | 3 | |
| B3-33 | 103N | 181C | 5 | 1 → 4 | 1 → 4 | |
| B1-49 | 101E | 190S | 3 → 5 | 3 → 4 | 4 → 5 | |
| B3-31 | 181I | 103N | 4 → 5 | 5 | 5 | |
| B2-07 | 101H, 188L, 238T | 98G, 179D, 181C, 190A | 5 | 3 → 5 | 5 | |
| B1-51 | 181C | 98G, 101E | 4 → 5 | 4 → 5 | 4 → 5 | |
| B3-26 | 103N, 181C | 190A, 238T | 5 | 4 | 4 → 5 | |
| B1-43 | 190S | 101E | 5 | 2 → 4 | 3 → 5 | |
| B2-11b | 190E | 230I | 5 | 4 → 5 | 5 | |
| B1-35 | 103N, 181C | 221Y | 5 | 4 | 4 → 5 | |
| B3-34 | 103N, 179L | 181C | 5 | 2 → 4 | 3 → 5 | |
| B1-33 | 103N, 238N | V179L | 5 | 1 → 2 | 1 → 3 | |
| B2-01 | 181C, 188H, 190A | V108I, H221Y | 5 | 4 → 5 | 5 | |
| B1-44 | 103N, 108I, 225H | 221Y | 5 | 1 → 2 | 1 → 3 | |
| B1-16 | 103N, 181C, 188C | 106A, 190A | 5 | 4 | 4 → 5 | |
| Samples for which Sanger sequencing reported higher levels of resistance to ≥1 NNRTIs | ||||||
| B3-29 | 101E, 190A | 103N, 181C | 5 | 5 → 4 | 5 | |
| B1-37 | 181C | 101E, 103N | 221Y | 5 → 4 | 4 | 5 |
| Samples for which Sanger sequencing or NGS detected different DRMs but for which levels of NNRTI resistance were the same | ||||||
| B2-32 | 100I, 238T | 103N | 5 | 4 | 5 | |
| B3-42 | 188L | 103N | 5 | 2 | 5 | |
| B3-36 | 98G, 101E, 103N, 190A | 225H | 5 | 4 | 5 | |
| B2-28 | 179E, 188L | 108I | 5 | 3 | 5 | |
| B2-29 | 98G, 103N, 108I, 221Y, 227L | 238N | 5 | 3 | 4 | |
| B1-04 | 100I, 103N, 225H | 108I | 5 | 4 | 5 | |
| B2-49 | 101P, 230L, 238N | 101E, 138K, 181C | 5 | 5 | 5 | |
a
Predicted levels of drug resistance according to the HIVDB genotypic resistance interpretation system, which were scored as follows: 1 for susceptible, 2 for potential low-level resistance, 3 for low-level resistance, 4 for intermediate resistance, and 5 for high-level resistance. EFV, efavirenz; ETR, etravirine; RPV, rilpivirine.
b
Sample B2-11 had evidence for an APOBEC-mediated G-to-A hypermutation. Both G190E (which was also detected by Sanger sequencing) and M230I (which was detected only by NGS) are DRMs that occur in the APOBEC dinucleotide context.