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).
Prevalence and characteristics of HIV drug resistance among antiretroviral treatment (ART) experienced adolescents and young adults living with HIV in Ndola, Zambia.
Abstract: Common TAMs were K70RTQNE (32.8%), K219QE (22.4%), D67N (17.2%) and T215IT (15.5%).
Result:
Discussion: In terms of HIVDR to NRTI, the prevalence of any TAMs was at 32.8% and the most common TAM's were K70R/T/Q/N/E (32.8%), K219Q/E (22.4%), D67N (17.2%), T215IT (15.5%) and M41L (5.2%).
Discussion: The TAMs of K70R/T/Q/N/E, K219Q/E, and D67N in combination effectively reduce the potency of zidovudine in a second line combination.
Patterns of acquired HIV-1 drug resistance mutations and predictors of virological failure in Moshi, Northern Tanzania.
HIV-1 drug resistance testing is essential for heavily-treated patients switching from first- to second-line regimens in resource-limited settings: evidence from routine clinical practice in Cameroon.
Abstract: Thymidine-analogue mutations (TAMs)-1 [T215FY (46.53%), M41 L (22.77%), L210 W (8.91%)], with cross-resistance to AZT and TDF, were higher compared to TAMs-2 [D67N (21.78%), K70R (19.80%), K219QE (18.81%)].
Result: Of note, TAMs-1 were predominant (T215F/Y: 46.5%; M41 L: 22.8%; L210 W: 8.9%) and associated with higher levels of resistance to both AZT and TDF; as compared to TAMs-2 that had relatively lower prevalence (D67N: 21.8%; K70R: 19.8%; K219Q/E: 18.8%) and were associated preferentially with AZT/D4T-resistance.
Persistence of Human Immunodeficiency Virus-1 Drug Resistance Mutations in Proviral Deoxyribonucleic Acid After Virologic Failure of Efavirenz-Containing Antiretroviral Regimens.
PMID: 30863788
2019
Open forum infectious diseases
Result: For a number of TDRMs, no loss could be observed during the observation period (S1 Table) and, according to their maximal duration of observation, the following TDRMs seem to survive for lengthy periods in the absence of ART: the NRTI resistance mutations D67N (5.9 years), K70R (6.9 years), F77L (10.2 years), T215E (5.9 years) and K219Q (5.9 years), the NNRTI resistance mutations A98G (6.5 years) and Y188L (5.9 years) as well as the PI mutations I54L (5.9 years) and L90M (8.4 years) (S1 Table).
Result: The presence of three or more TDRMs was mainly due to the accum
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
Conclusion: At that time, resistance testing showed NRTI (M184V, T69D, T215S, D67N, K219Q), NNRTI (Y181C, Y188L, H221Y) and PI (L10I, D30N, K20T, L33F, K43T, N88D) resistance, with PI resistance to nelfinavir.
Table: K219Q
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
Result: When DRM5% were assessed, double the number of NRTI mutations were found (n = 22), mostly represented by K65R (n = 4/22, 18.2%) and the TAMs D67N and K219EQ (Figure 1b).
Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I.
PMID: 31430369
2019
The Journal of antimicrobial chemotherapy
Result: Pre-existing NRTI-R substitutions were observed in 16% (89/543) of BIC/FTC/TAF-treated participants; the most frequently detected substitutions were M184V/I in 10% (54/543) and thymidine analogue mutations (TAMs; M41L, D67N, K70R, L210W, T215Y/F and K219Q/N/E/R) in 8.8% (48/543).