Discussion: Common INSTI RAMS include R263K, Q148H/R/K, G118R, G140A/S/C, E138A/K/T, N155H, and Y143C/R.
HIV-1 Integrase Inhibitors That Are Active against Drug-Resistant Integrase Mutants.
PMID: 32601157
2020
Antimicrobial agents and chemotherapy
Abstract: Both were superior to DTG, as evidenced by the data obtained with the IN mutant T66I/L74M/E138K/S147G/Q148R/S230N, which was selected by CAB using an EVG-resistant lab strain.
Virologic failure after 48 weeks of raltegravir-based regimen in low HIV-1 incidence setting.
Discussion: N155H was the main mutation pathway for virologic failure, followed by Q143R and Q148R/H mutation pathways.
Drug Resistance Mutations Against Protease, Reverse Transcriptase and Integrase Inhibitors in People Living With HIV-1 Receiving Boosted Protease Inhibitors in South Africa.
Discussion: N155H, Q148H/R/K, and Y143R/C/H are the three major recognized pathways of genotypic resistance against InSTIs.
Resistance to HIV integrase strand transfer inhibitors in Argentina: first interim survey.
PMID: 31037930
2019
Revista espanola de quimioterapia
Abstract: Predominant major mutations were N155H (35.1%), Q148H/R (15.8%) and G140A/S (14%).
Introduction: Different pathways against first-generation InSTIs were identified whose primary mutations include the substitutions N155H, Q148K/R/H, and Y143R/C.
Result: Predominant combinations of mutations were 140A/S + Q148H/R and N155H + G163K/R.
Result: Predominant major integrase resistance mutations were N155H (35.1%), Q148H/R (15.8%) and PMID: 30803972
2019
Antimicrobial agents and chemotherapy
Abstract: HIV-2 integrase mutants G140S/Q148R and G140S/Q148H were 34- and 110-fold resistant to bictegravir, respectively; other resistance-associated mutations conferred <=5-fold changes in bictegravir susceptibility.
Clinical experience with integrase inhibitors in HIV-2-infected individuals in Spain.
PMID: 30753573
2019
The Journal of antimicrobial chemotherapy
Abstract: INSTI resistance changes were recognized in 12 patients: N155H (5), Q148H/R (3), Y143C/G (3) and R263K (1).
Predicted antiviral activity of tenofovir versus abacavir in combination with a cytosine analogue and the integrase inhibitor dolutegravir in HIV-1-infected South African patients initiating or failing first-line ART.
PMID: 30380053
2019
The Journal of antimicrobial chemotherapy
Abstract: One of 607 integrase sequences carried a DRM20% (Q148R).
Result: Among ART-exposed participants, only one had low-level resistance to dolutegravir (Q148R) among participants with available consensus sequence covering the integrase (n = 83).
Result: Fifteen participants had integrase DRM20% (15/83, 18.1%), including Q148R conferring low-level resistance to dolutegravir, and some accessory integrase mutations were also found: L74I/M (n = 12/15, 80.0%), E157Q (n = 1) and G163R (n = 1).
Discussion: We did observe Q148R, which is associated with high-level dolutegravir resistance
Drug resistance emergence in macaques administered cabotegravir long-acting for pre-exposure prophylaxis during acute SHIV infection.
Introduction: An additional concern is the lack of information on the mutations selected with CAB in vivo and their potential impact on resistance to other INSTIs, as only two cases of CAB resistance have been reported in HIV-infected patients treated with CAB, both mediated by integrase mutation Q148R.
Discussion: In humans, treatment with CAB or CAB LA has been associated with rare instances of selection of Q148R.
Development of the R263K Mutation to Dolutegravir in an HIV-1 Subtype D Virus Harboring 3 Class-Drug Resistance.
PMID: 30648124
2019
Open forum infectious diseases
Introduction: DTG appears to have a high genetic barrier to resistance, unlike the other drugs within the INSTI class, raltegravir and elvitegravir, which select for major resistance mutations such as N155H, Y143H/R/C, G140A/S, and Q148H/R/K.