Method: We followed-up the 50 mutations of resistance present at 32 positions: associated with in vitro or in vivo resistance to HIV-1 integrase inhibitors: H51Y, T66I/A/K, V72I, L74I/A/M, E92Q, T97A, T112I, F121Y, T125K, A128T, E138 K/A/D, G140R/C/H, Y143C/H/R, Q146K/P, S147G, Q148K/R/H, V151I, PMID: 20610719
2010
Journal of virology
1Abstract: Viruses containing G118R and E138K remained largely susceptible to both RAL and EVG, suggesting a unique interaction between this second-generation INSTI and the enzyme may be defined by these residues as a potential basis for the increased intrinsic affinity and longer ""off"" rate of MK-2048."
Abstract: Here, we report the identification of mutations (G118R and E138K) which confer resistance to MK-2048 and not to RAL or EVG.
Abstract: The subsequent selection of E138K partially restored replication capacity to approximately 13% of wt levels and increased resistance to MK-2048 to approximately 8-fold.
Effect of raltegravir resistance mutations in HIV-1 integrase on viral fitness.
PMID: 20634701
2010
Journal of acquired immune deficiency syndromes (1999)
Abstract: Fitness was partially restored by the presence of additional RAL resistance mutations at positions G140S and E92Q or E138K, respectively.
Result: By contrast, the E92Q/N155H mutant was fitter than the E138K/Q148H mutant both in the absence and presence of 5.0 microM RAL (Table 2).
Result: However, the E138K/Q148H mutant was less fit than G140S/Q148H in the absence and presence of drug.
Result: In the presence of raltegravir, the E138K/Q148H had a 3.0-fold relative fitness advantage over the
Distinct mutation pathways of non-subtype B HIV-1 during in vitro resistance selection with nonnucleoside reverse transcriptase inhibitors.
PMID: 20805392
2010
Antimicrobial agents and chemotherapy
Abstract: Y181C was the dominant mutation in the resistance selection with etravirine (ETV) in subtype A, and E138K/H221Y were the mutations detected in the breakthrough viruses from subtype C viruses with ETV.
Dynamic escape of pre-existing raltegravir-resistant HIV-1 from raltegravir selection pressure.
Abstract: This update includes 9 new mutations- E138G and E138K for etravirine (Haddad M et al, CROI, 2010; Abstract 574, and Vingerhoets J et al, Antivir Ther, 2010;15 [Suppl 2]:A125); E92Q for raltegravir (Geretti AM et al, Antivir Ther, 2010;15 [Suppl 2]:A62; Cooper et al, N Engl J Med, 2008;359:355-365; and Malet I et al, Antimicrob Agents Chemother, 2008;52:1351-1358); and M36L, M36V, H69R, L89I, L89M, and L89V for tipranavir/ritonavir.
Secondary mutations in viruses resistant to HIV-1 integrase inhibitors that restore viral infectivity and replication kinetics.
Abstract: In contrast, Q148K/G140S and Q148R/E138K had nearly equivalent or slightly reduced fold resistance to the INI compared with their respective Q148 primary mutants, and had increases in infectivity and replication kinetics.
Abstract: Relative to Q148K alone, Q148K/E138K had 2- and >6-fold increases in resistance to S-1360 and S/GSK-364735, respectively, and the double mutant had slightly better infectivity and replication kinetics.
Abstract: Secondary amino acid substitutions E138K or G140S were observed when passage with INI was continued.
Characterization and structural analysis of HIV-1 integrase conservation.
Result: Among mutations selected by raltegravir or elvitegravir that have not been shown to directly reduce susceptibility, L74R, Q95K, E138A/K, and H183P were conserved, whereas V54I, L68V, L74M, T97A, V151I, G163R, and I203M were present in approximately 1% to 2% of isolates from untreated persons (Figure 1).
Discussion: Most accessory INI-resistance mutations including L74R, Q95K, E138A/K, H183P,
ViMRT
HIV mutation literature information.
PMID: 
2010
PloS one
