Stanford University HIV Drug Resistance Database - A curated public database designed to represent, store, and analyze the divergent forms of data underlying HIV drug resistance.

NRTI Resistance Notes

Last updated on Feb 28, 2014
PositionConsAAComment
40EFE40F is a nonpolymorphic mutation selected by AZT and d4T. It usually occurs in combination with M41L, L210W and T215Y. In this context it is associated with reduced susceptibility to each of the NRTIs.
41MIM41I is usually an artifact resulting from APOBEC3G-mediated hypermutation.
41MLM41L is a TAM that usually occurs with T215Y. Together, M41L and T215Y confer high-level resistance to AZT and d4T and intermediate-level resistance to ddI, ABC and TDF. However, viruses with M41L + T215Y + M184V will exhibit intermediate-level resistance to AZT and d4T and low-level resistance to TDF.
62AVA62V is an accessory mutation that often occurs in combination with the multinucleoside resistance mutations K65R or Q151M-. Alone it does not reduce NRTI susceptibility. A62V is widespread in subtype A viruses in former Soviet Union countries but is otherwise nonpolymorphic.
65KEK65R causes intermediate/high-level resistance to TDF, ddI, ABC and d4T (2 to 3-fold reduced susceptibility) and low to intermediate-level resistance to 3TC and FTC (5 to 7-fold reduced susceptibility). K65R increases susceptibility to AZT. K65E is an extremely rare NRTI-selected mutation with markedly reduced replication fitness.
65KNK65R causes intermediate/high-level resistance to TDF, ddI, ABC and d4T (2 to 3-fold reduced susceptibility) and low to intermediate-level resistance to 3TC and FTC (5 to 7-fold reduced susceptibility). K65R increases susceptibility to AZT. K65N is a rare mutation with effects on NRTI susceptibility that are similar but weaker to those of K65R.
65KRK65R causes intermediate/high-level resistance to TDF, ddI, ABC and d4T (2 to 3-fold reduced susceptibility) and low to intermediate-level resistance to 3TC and FTC (5 to 7-fold reduced susceptibility). K65R increases susceptibility to AZT.
67DEGSTQHD67N is a nonpolymorphic TAM associated with low-level resistance to AZT and d4T. When present with other TAMs, it reduces susceptibility to ABC, TDF and ddI. D67G/E/S/T/H are nonpolymorphic NRTI-selected mutations that also generally occur in viruses with multiple TAMs.
67DND67N is a nonpolymorphic TAM associated with low-level resistance to AZT and d4T. When present with other TAMs, it reduces susceptibility to ABC, TDF and ddI.
67DdeleteAmino acid deletions (d) between codons 66 to 71 are rare and usually occur in combination with multiple TAMs, the Q151M mutation complex, or K65R. Deletions at position 67 are more often associated with multiple TAMs. Deletions at position 69 are more often associated with either the Q151M complex or K65R.
69TDT69D is a nonpolymorphic mutation that reduces susceptibility to ddI and possibly d4T.
69TGT69G is a rare polymorphic mutation that usually occurs in viruses with a deletion at codon 67 and multiple NRTI-resistance mutations. It is associated with reduced susceptibility to ddI, d4T, ABC and possibly TDF.
69TNT69N is a relatively non-polymorphic mutation weakly selected in patients receiving NRTIs. Their effects on NRTI susceptibility have not been well studied.
69TSAIET69S/A/I/E are relatively non-polymorphic mutations weakly selected in patients receiving NRTIs. Their effects on NRTI susceptibility have not been well studied.
69TdeleteAmino acid deletions (d) between codons 66 to 71 are rare and usually occur in combination with multiple TAMs, the Q151M mutation complex, or K65R. Deletions at position 67 are more often associated with multiple TAMs. Deletions at position 69 are more often associated with either the Q151M complex or K65R.
69TinsertDouble amino acid insertions between codons 66 to 71 most often align to codon 69 and occur in less than 1% 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.
70KEGK70E/G cause low/intermediate-level resistance (2 to 3-fold reduced susceptibility) to TDF, ABC, DDI and possibly 3TC and FTC. K70E increases susceptibility to AZT.
70KQNSTK70R causes intermediate-level resistance to AZT and possibly low-level resistance to d4T and TDF. K70E/G cause low/intermediate-level resistance (2 to 3-fold reduced susceptibility) to TDF, ABC, DDI and possibly 3TC and FTC. K70E increases susceptibility to AZT. K70Q/N/S/T are rare nonpolymorphic NRTI-selected mutations that appear to have resistance profiles similar to K70E/G.
70KRK70R causes intermediate-level resistance to AZT and possibly low-level resistance to d4T and TDF.
74LIVL74V/I cause high-level resistance to ddI and intermediate-level resistance to ABC. L74V increases susceptibility to AZT and TDF, but this increase is of uncertain clinical significance.
75VIV75I is a relatively nonpolymorphic accessory mutation that usually occurs in combination with the multi-nucleoside resistance mutations F77L, F116Y and Q151M. V75I occasionally occurs alone and in this context its clinical significance is unknown.
75VMV75M appears to cause intermediate-level d4T resistance and low-level ddI resistance.
75VSALV75S/A/L are nonpolymorphic mutations that appear to reduce susceptibility to d4T and ddI.
75VTV75T causes high-level d4T resistance and intermediate-level ddI resistance.
77FLF77L usually occurs in combination with the multinucleoside resistance mutations F116Y and Q151M.
115YFY115F causes intermediate-level resistance to ABC and low-level resistance to TDF.
116FYF116Y usually occurs in combination with the multinucleoside resistance mutations F77L and Q151M.
151QLQ151M causes intermediate/high-level resistance to AZT, ddI, d4T and ABC and low-level resistance to TDF, 3TC and FTC. In combination with mutations at the associated positions 75, 77, and 116, Q151M confers high-level resistance to AZT, ddI, d4T and ABC and intermediate-level resistance to TDF, 3TC and FTC. Q151L is an extremely rare transitional mutation that may precede the emergence of the Q151M.
151QMQ151M causes intermediate/high-level resistance to AZT, ddI, d4T and ABC and low-level resistance to TDF, 3TC and FTC. In combination with mutations at the associated positions 62, 75, 77, and 116, Q151M confers high-level resistance to AZT, ddI, d4T and ABC and intermediate-level resistance to TDF, 3TC and FTC.
184MVIM184V/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 reductions in HIV-1 replication. In combination with K101E or E138K, M184I synergistically reduces RPV susceptibility.
210LFSL210F/S are rare mutations not associated with NRTI-resistance.
210LWL210W usually occurs in combination with M41L and T215Y. The combination of M41, L210W and T215Y causes high-level resistance to AZT and d4T and intermediate to high-level resistance to ddI, ABC and TDF.
215TFT215F is a TAM that causes intermediate/high-level resistance to AZT and d4T and low-level resistance to ABC, ddI and TDF. Compared with T215Y, T215F occurs more commonly with the Type II TAMs (D67N, K70R, and/or K219E) and in this context, it affects susceptibility to TDF, ABC, and ddI less markedly than T215Y.
215TSCDEIVALNT215Y/F cause intermediate/high-level resistance to AZT and d4T and low-level resistance to ABC, ddI and TDF. T215S/C/D/E/I/V/N/A/L do not reduce NRTI susceptibility but arise from viruses that once contained T215Y/F. The presence of one of these revertant mutations suggests the possibility that the patient may have once harbored a majority virus population with T215Y/F.
215TYT215Y is a TAM which causes intermediate/high-level resistance to AZT and d4T and low-level resistance to ABC, ddI, and TDF.
219KNRK219N/R are accessory TAMS that usually occur in combination with multiple other TAMs.
219KQEK219Q/E are accessory TAMS associated with reduced susceptibility to AZT and possibly d4T.
219KWK219W is an uncommon NRTI-selected mutation