Pharmaceutical, clinical, and resistance information on doravirine, a novel non-nucleoside reverse transcriptase inhibitor for the treatment of HIV-1 infection.
Introduction: Finally, substitutions that disrupt the NNRTI-binding pocket, such as Y188L and M230L, confer pan-resistance against all NNRTIs.
Introduction: Other single substitutions including G190E/S, V106A, Y188L, and M230L reduced DOR susceptibility >10-fold.
Introduction: The G190S, Y188L, and M230L substitutions confer >95-fold resistance.
Introduction: The highest levels of reduction in DOR susceptibility were associated with V106A or Y188L or each of these two mutations in combination with at least
HIV-1 reverse transcriptase and protease mutations for drug-resistance detection among treatment-experienced and naive HIV-infected individuals.
Result: However, in the Y188L RT (Figure 4H), the compound 10p lost the hydrogen bond between 4'-CN and Y188 and decreased pi-pi stacking interactions.
Result: That might explain the higher antiviral activity against the E138K mutant than against the Y188L mutant.
Result: These compounds were also tested in the MT-4 cells for their activities against the single mutant (L100I, E138K, Y181C, K103N, Y188L) and double RT mutant (K103N + Y181C, F227L +
Pharmacophore-fusing design of pyrimidine sulfonylacetanilides as potent non-nucleoside inhibitors of HIV-1 reverse transcriptase.
Comparison of HIV drug resistance profiles across HIV-1 subtypes A and D for patients receiving a tenofovir-based and zidovudine-based first line regimens in Uganda.
Result: However, when we compared individual mutations we found that M184V/I (p = 0.015), Y188L (p = 0.008) and TAMs (p = 0.011) were significantly more common in Subtype A as compared to Subtype D and others.
Discussion: However, M184V/I (67 (55.8%), p = 0.015), Y188L (9 (100%), p = 0.008) and TAMs (44 (51.8%), p = 0.011) were noted more in subtype A, but the number of occurrence of these mutations could not affect the overall association, therefore the study finds these individual mutation observations statistically irrelevant.
Trend of HIV-1 drug resistance in China: A systematic review and meta-analysis of data accumulated over 17 years (2001-2017).
Human Immunodeficiency Virus-1 Viral Load Is Elevated in Individuals With Reverse-Transcriptase Mutation M184V/I During Virological Failure of First-Line Antiretroviral Therapy and Is Associated With Compensatory Mutation L74I.
PMID: 31774913
2020
The Journal of infectious diseases
Result: The following NNRTI mutations were also associated: A98G, L100I, K103R, V108I, Y181C, Y188L, G190A, P225H, L228R, and M230L.
Pretreatment HIV drug resistance spread within transmission clusters in Mexico City.
PMID: 31819984
2020
The Journal of antimicrobial chemotherapy
Result: Other commonly observed NNRTI DRMs included G190A, Y188L, Y181C and K101E (Figure 1c).
Result: Other frequently shared DRMs included: reverse transcriptase (RT) Y188L (11/175), RT T215S/C (24/175) and protease M46I (19/175), mostly at >=20% within-host frequency; and RT D67N/G/E (56/175) and RT P225H (16/175) as low-frequency variants.
Drug Resistance Mutations Against Protease, Reverse Transcriptase and Integrase Inhibitors in People Living With HIV-1 Receiving Boosted Protease Inhibitors in South Africa.
Result: Y188L occurred in five (5%) patients receiving AZT plus 3TC, and in two (2%) patients receiving TDF plus ATV/r, and in one (1%) patient receiving ABC plus 3TC.
Table: Y188L
Discussion: The group receiving AZT plus 3TC or ABC plus 3TC showed the highest rates of NNRTI mutations such as P225H, V106M, E138A/G/K/Q, G190A/S, and Y188L occurred most frequently in patients receiving AZT plus 3TC or ABC plus 3TC.
Prevalence of doravirine-associated resistance mutations in HIV-1-infected antiretroviral-experienced patients from two large databases in France and Italy.
PMID: 31976534
2020
The Journal of antimicrobial chemotherapy
Abstract: RESULTS: The frequencies of doravirine-associated resistance mutations (total dataset versus NNRTI-failing patients) were: V106A/M, 0.8% versus 2.6%; V108I, 3.3% versus 9.2%; Y188L, 1.2% versus 2.6%; G190S, 0.3% versus 2.1%; F227C/L/V, 0.5% versus 1.8%; M230I/L, 2.8% versus 0%; L234I, 0.1% versus 0.5%; K103N + Y181C, 3.9% versus 3.9%; K103N + P225H, 2.9% versus 4.7%; and K103N + L100I, 1.7% versus 3.9%, with a significantly higher proportion of these mutations in the
HIV mutation literature information.
PMID: 
2020
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