Result: In NRTI mutations, T215I/Y/S/N/F/E had the highest percentage (31.2%) in subtype B, whereas M184I/V had the most predominant percentage (43.8-73.3%) in CRF01_AE and other subtypes (Table 2 and Appendix 20).
Result: The top NRTI mutations identified in ART-naive and ART-treated individuals were M184V/I (16.3% and 41.8%) and T215I/Y/S/D/F (20.9% and 9.5%), and the top NNRTI mutations were K103N/S (18.7% and 40.5%), Y181C/I (14.0% and 22.2%), and G190A/S (9.5% and 22.2%, respectively).
Antiviral Activity of Tenofovir Alafenamide against HIV-1 with Thymidine Analog-Associated Mutations and M184V.
PMID: 31988104
2020
Antimicrobial agents and chemotherapy
Abstract: The susceptibilities to antiviral drugs of site-directed mutants (SDMs) and patient-derived mutants containing combinations of TAMs (M41L, D67N, K70R, L210W, T215Y, and K219Q) with or without the M184V mutation (TAMs+-M184V) were evaluated using either 5-day multicycle (MC; n = 110) or 2-day single-cycle (SC; n = 96) HIV assays.
HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study.
High resistance to reverse transcriptase inhibitors among persons infected with human immunodeficiency virus type 1 subtype circulating recombinant form 02_AG in Ghana and on antiretroviral therapy.
Discussion: T215Y/F and K219E are major TAMs which give rise to high-level resistance to Zidovudine and Stavudine, especially when the mutations occur in concert with accessory TAMs like M41L, D67N, and K70R.
Discussion: Other mutations detected in this study, which have been shown to confer resistance to NRTIs, were M184I, T69N, L74I, M41L, K70R/E, T215Y/F, and K219E.
High prevalence of integrase mutation L74I in West African HIV-1 subtypes prior to integrase inhibitor treatment.
PMID: 32105319
2020
The Journal of antimicrobial chemotherapy
Table: T215Y
Defective Strand-Displacement DNA Synthesis Due to Accumulation of Thymidine Analogue Resistance Mutations in HIV-2 Reverse Transcriptase.
Abstract: In HIV-1, resistance to zidovudine and other thymidine analogues is conferred by different combinations of M41L, D67N, K70R, L210W, T215F/Y, and K219E/Q (designated as thymidine analogue resistance-associated mutations (TAMs)).
Abstract: Unlike in HIV-2, substitutions M41L/T215Y and D67N/K70R/T215Y/K219Q had no effect on the strand displacement activity of HIV-1BH10 RT.
Prevalence and characteristics of HIV drug resistance among antiretroviral treatment (ART) experienced adolescents and young adults living with HIV in Ndola, Zambia.
Result: Additionally, 13.3% (6 out of the 45) needing first line drug change had the type 2 TAMs combination of T215Y, D67N and K70RTQNE which in combination diminish the effectiveness of zidovudine.
Discussion: The high prevalence of individual TAMs (D67N and K70R) or TAMs in combination (M41L with T215Y) reduces susceptibility to Zidovudine (a key drug for most second line regimens).
Nucleocapsid Protein Precursors NCp9 and NCp15 Suppress ATP-Mediated Rescue of AZT-Terminated Primers by HIV-1 Reverse Transcriptase.
PMID: 32747359
2020
Antimicrobial agents and chemotherapy
Abstract: Clinically relevant combinations of TAMs, such as M41L/T215Y or D67N/K70R/T215F/K219Q, enhance the ATP-mediated excision of AZT monophosphate (AZTMP) from the 3' end of the primer, allowing DNA synthesis to continue.
Abstract: In HIV-1, development of resistance to AZT (3'-azido-3'-deoxythymidine) is mediated by the acquisition of thymidine analogue resistance mutations (TAMs) (i.e., M41L, D67N, K70R, L210W, T215F/Y, and K219E/Q) in the viral reverse transcriptase (RT).
Pre-treatment drug resistance and HIV-1 genetic diversity in the rural and urban settings of Northwest-Cameroon.
Discussion: In combination, M41L plus T215Y confer intermediate / high-level resistance to Zidovudine (AZT) and Stavudine (d4T) and contribute to reduced Didanosine (ddI), Abacavir (ABC) and Tenofovir (TDF) susceptibility.
Discussion: The mutation M41L is a TAM that usually occurs with T215Y.
Patterns of acquired HIV-1 drug resistance mutations and predictors of virological failure in Moshi, Northern Tanzania.
Discussion: Two of these samples had M41L and T215Y TAMs, a combination which further enhances cross-resistance to all US FDA approved NRTIs, a phenomenon known as Multi-NRTI resistance.
HIV mutation literature information.
PMID: 
2020
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