Background:  Clinically oriented lists of HIV drug resistance mutations have limited utility for surveillance of transmitted resistance. Inclusion of mutations that occur naturally without drug pressure lead to overestimates. In 2007, a World Health Organization (WHO) working group proposed and published a mutation list for surveillance of transmitted drug-resistant HIV. An updated list based on new data is now proposed based on these criteria:  Mutations are associated with HIV drug resistance (defined as inclusion in ≥3 expert lists among those listed in the method below), selected by ART, non-polymorphic (should not occur without drug pressure >0.5% in any HIV-1 subtype with >1000 sequences analyzed, or >1% with fewer sequences), parsimonious (excluding rare mutations occurring at <1% among treated patients) and applicable to all subtypes.

Methods:  We examined 5 expert lists (International AIDS Society–USA, Los Alamos, Stanford HIV Database, Agence Nationale Reserche sur le Sida, and Rega Institute). We evaluated mutations in ≥3 lists for frequency of selection with ART and non-polymorphism using the Stanford HIV RT and Protease Sequence database, excluding any sequence from an untreated person with ≥2 drug resistance mutations known to be non-polymorphic, and from areas where primary HIV drug resistance is >5%. We analyzed the following numbers of subtype B and non-B sequences: 7395 and 7710 from PI-naive persons; and 5539 and 5982 from RTI-naïve persons. Numbers of non-B sequences from untreated persons were:  A, 1,524; AE, 890; AG, 1,415; C, 2,145; D, 512; F, 605; G, 619. Non-polymorphic mutations associated with ART were included in the list.

Results:  Nearly twice the numbers of B and non-B sequences were analyzed for the new list than for the 2007 list. The list includes these mutations (new mutations italicized):  PI—23I, 24I, 0N, 32I, 46I/L, 47V/A, 48M/V, 50V/L, 53L/Y, 54V/M/L/T/S/A, 58E, 73S/T/C/A, 76V, 82A/F/L/T/S/M/C, 83D, 84V/A/C, 85V, 88D/S, 90M; NRTI—41L, K65R/N, 67N/G/E/del, 69D/G/N/ins, 70E/R/G, 74I/V, 75T/A/M/S, 77L, 115F, 116Y, 151M, 184V/I, 210W, 215C/D/E/F/V/Y/S/I, 219E/Q/N/R; NNRTI—100I, 101E, 103N, V106A/M, 179F, 181C/I/V, 188L/C, 190A/S/E/Q/C, 225H, 230L, 236L.

Conclusions:  The 2007 WHO list was used in several published surveys and has facilitated comparability of results and minimized misclassification of transmitted resistance. The new list, based on substantially more sequences, includes several new mutations. The list will continue to be updated annually and made publicly available.