NRTI Resistance Notes
Last updated on May 29, 2012
| Resistance Matrix | Resistance Mutation Comments | Resistance Mutation Scores | Drug Summaries |
| Position | Cons | AA | Comment |
| 40 | E | F | E40F is a nonpolymorphic mutation selected by AZT and d4T. It usually occurs in combination with M41L, L210W, and T215Y and facilitates TAMs-associated NRTI-resistance. |
| 41 | M | I | M41L usually occurs with T215Y. This combination of mutations confers high-level resistance to AZT and d4T and low level resistance to ddI, ABC, and TDF. M41I is an artifact resulting from APOBEC3G-mediated hypermutation. |
| 41 | M | L | M41L usually occurs with T215Y. This combination of mutations confers high-level resistance to AZT and d4T and low level resistance to ddI, ABC, and TDF. |
| 62 | A | V | A62V increases Q151M-associated multinucleoside resistance and compensates for the replication defect observed with K65R. |
| 65 | K | N | K65R causes intermediate resistance to ddI, ABC, 3TC, FTC, and TDF; low-level resistance to d4T; and increased susceptibility to AZT. K65N is an extremely rare mutation with similar but weaker effects on NRTI susceptibility than K65R. |
| 65 | K | R | K65R causes intermediate resistance to ddI, ABC, 3TC, FTC, and TDF; low-level resistance to d4T; and increased susceptibility to AZT. |
| 66 | K | d | Amino acid deletions (d) between codons 66 to 71 are rare and usually only occur in combination with either multiple TAMs or the Q151M complex and, in these contexts, they are often associated with high-level multi-NRTI resistance |
| 66 | K | i | Double amino acid insertions (i) between codons 66 to 71 most often align to codon 69 and occur in about 1%-2% of heavily treated persons. Together with TAMs, they confer high-level resistance to AZT, d4T, ddI, ABC, and TDF, and intermediate/high-level resistance to 3TC and FTC. Single amino acid insertions generally occur with Type II TAMs and have a similar, but weaker, effect on susceptibility. |
| 67 | D | EGSTQ | D67N contributes resistance to AZT and d4T. D67E/G/S/T/Q generally occur in viruses with multiple NRTI-resistance mutations and their effects on drug susceptibility have not been well-characterized. |
| 67 | D | N | D67N contributes resistance to AZT and d4T. |
| 67 | D | d | Amino acid deletions (d) between codons 66 to 71 are rare and usually only occur in combination with either multiple TAMs or the Q151M complex and, in these contexts, they are often associated with high-level multi-NRTI resistance |
| 67 | D | i | Double amino acid insertions (i) between codons 66 to 71 most often align to codon 69 and occur in about 1%-2% of heavily treated persons. Together with TAMs, they confer high-level resistance to AZT, d4T, ddI, ABC, and TDF, and intermediate/high-level resistance to 3TC and FTC. Single amino acid insertions generally occur with Type II TAMs and have a similar, but weaker, effect on susceptibility. |
| 68 | S | d | Amino acid deletions (d) between codons 66 to 71 are rare and usually only occur in combination with either multiple TAMs or the Q151M complex and, in these contexts, they are often associated with high-level multi-NRTI resistance |
| 68 | S | i | Double amino acid insertions (i) between codons 66 to 71 most often align to codon 69 and occur in about 1%-2% of heavily treated persons. Together with TAMs, they confer high-level resistance to AZT, d4T, ddI, ABC, and TDF, and intermediate/high-level resistance to 3TC and FTC. Single amino acid insertions generally occur with Type II TAMs and have a similar, but weaker, effect on susceptibility. |
| 69 | T | D | T69D is associated with decreased susceptibility to ddI and d4T. |
| 69 | T | G | T69G usually occurs in combination with multiple NRTI-resistance mutations often including a deletion at codon 67. By itself it reduces ddI and ABC susceptibility. |
| 69 | T | NSAI | T69D is associated with decreased susceptibility to ddI and d4T. T69N/S/A/I are NRTI-selected mutations but their effect on NRTI susceptibility have not been well characterized. |
| 69 | T | d | Amino acid deletions (d) between codons 66 to 71 are rare and usually only occur in combination with either multiple TAMs or the Q151M complex and, in these contexts, they are often associated with high-level multi-NRTI resistance |
| 69 | T | i | Double amino acid insertions (i) between codons 66 to 71 most often align to codon 69 and occur in about 1%-2% of heavily treated persons. Together with TAMs, they confer high-level resistance to AZT, d4T, ddI, ABC, and TDF, and intermediate/high-level resistance to 3TC and FTC. Single amino acid insertions generally occur with Type II TAMs and have a similar, but weaker, effect on susceptibility. |
| 70 | K | EG | K70E/G reduce TDF, ABC, DDI, and to a lesser extent 3TC and FTC susceptibility. |
| 70 | K | QNST | K70Q/N/S/T are rare non-polymorphic NRTI-selected mutations that appear to have similar but weaker phenotypic effects than K70E/G. |
| 70 | K | R | K70R causes intermediate resistance to AZT and low-level resistance to d4T and TDF. |
| 70 | K | d | Amino acid deletions (d) between codons 66 to 71 are rare and usually only occur in combination with either multiple TAMs or the Q151M complex and, in these contexts, they are often associated with high-level multi-NRTI resistance |
| 70 | K | i | Double amino acid insertions (i) between codons 66 to 71 most often align to codon 69 and occur in about 1%-2% of heavily treated persons. Together with TAMs, they confer high-level resistance to AZT, d4T, ddI, ABC, and TDF, and intermediate/high-level resistance to 3TC and FTC. Single amino acid insertions generally occur with Type II TAMs and have a similar, but weaker, effect on susceptibility. |
| 71 | W | d | Amino acid deletions (d) between codons 66 to 71 are rare and usually only occur in combination with either multiple TAMs or the Q151M complex and, in these contexts, they are often associated with high-level multi-NRTI resistance |
| 71 | W | i | Double amino acid insertions (i) between codons 66 to 71 most often align to codon 69 and occur in about 1%-2% of heavily treated persons. Together with TAMs, they confer high-level resistance to AZT, d4T, ddI, ABC, and TDF, and intermediate/high-level resistance to 3TC and FTC. Single amino acid insertions generally occur with Type II TAMs and have a similar, but weaker, effect on susceptibility. |
| 74 | L | IV | L74V causes high-level ddI and intermediate ABC resistance. L74I has similar but weaker phenotypic effects. |
| 75 | V | I | V75I increases Q151M-associated multinucleoside resistance. |
| 75 | V | TMAS | V75T/M reduce d4T and ddI susceptibility. V75A/S may have similar effects. |
| 77 | F | L | F77L increases Q151M-associated multinucleoside resistance. |
| 115 | Y | F | Y115F causes intermediate resistance to ABC and low-level resistance to TDF. |
| 116 | F | Y | F116Y increases Q151M-associated multinucleoside resistance. |
| 151 | Q | L | Q151M causes intermediate-to-high level resistance to AZT, ddI, d4T, and ABC, and low-level resistance to TDF, 3TC, and FTC. With changes at the associated positions 75, 77, and 116, Q151M confers high-level resistance to AZT, ddI, d4T, and ABC, and intermediate resistance to TDF, 3TC, and FTC. Q151L is a rarely observed transitional mutation that may precede the emergence of the Q151M. |
| 151 | Q | M | Q151M causes intermediate-to-high level resistance to AZT, ddI, d4T, and ABC, and low-level resistance to TDF, 3TC, and FTC. With changes at the associated positions 75, 77, and 116, Q151M confers high-level resistance to AZT, ddI, d4T, and ABC, and intermediate resistance to TDF, 3TC, and FTC. |
| 184 | M | VI | M184V/I cause high-level resistance to 3TC and FTC and low-level resistance to ddI and ABC. However, M184V/I are not contraindications to continued treatment with 3TC or FTC because they increase susceptibility to AZT, TDF, and d4T and are associated with clinically significant decreased HIV-1 replication. |
| 210 | L | W | L210W contributes resistance to each of the NRTIs except 3TC and FTC. It usually occurs with the mutations M41L and T215Y. |
| 215 | T | F | T215F causes AZT and D4T resistance and reduces susceptibility to ABC, ddI, and TDF particularly in combination with M41L and L210W. T215F occurs more commonly (than T215Y) with Type II TAMs. |
| 215 | T | SCDEIVNAL | T215Y/F cause AZT and D4T resistance and reduce susceptibility to ABC, ddI, and TDF. T215S/C/D/E/I/V/N/A/L do not decrease NRTI susceptibility but arise from viruses that once contained T215Y/F. |
| 215 | T | Y | T215Y causes AZT and D4T resistance and reduces susceptibility to ABC, ddI, and TDF particularly in combination with M41L and L210W. |
| 219 | K | DHW | K219W/H/D are uncommon NRTI-selected mutations. |
| 219 | K | NR | K219N/R occur commonly in heavily NRTI-treated patients. Their effect on NRTI susceptibility is uncertain. |
| 219 | K | QE | K219Q/E decrease AZT and probably d4T susceptibility when present with K70R or T215Y/F but have little if any effect on the remaining NRTIs. |