What is genotypic resistance?

What is genotypic resistance?

Genotypic resistance testing examines the genetic structure (genotype) of a patient’s HIV. A blood sample is taken from the patient, and the HIV is analyzed for the presence of specific genetic mutations that are known to cause resistance to specific drugs.

Which antiviral drug is thymidine analog?

A thymidine analog that inhibits DNA polymerase activity, trifluridine is an antiviral drug used primarily as a treatment of Herpes Simplex Virus (HSV-1 and HSV-2) and vaccinia virus [Drug Facts and Comparison (2001)].

What is a thymidine analogue?

Thymidine analogues are powerful tools when studying DNA synthesis including DNA replication, repair and recombination. However, these analogues have been reported to have severe effects on cell-cycle progression and growth, the very processes being investigated in most of these studies.

Is zidovudine a thymidine analog?

Zidovudine is an analog of thymidine that inhibits replication of the AIDS virus.

What is K65R mutation?

K65R is a relatively rare drug resistance mutation (DRM) selected by the NRTIs tenofovir, didanosine, abacavir and stavudine and confers cross-resistance to all NRTIs except zidovudine. Selection by other NRTIs is uncommon.

What is the difference between thymine and thymidine?

The key difference between thymine and thymidine is that thymine is a nucleobase, whereas thymidine is a nucleoside. A nucleotide contains a nucleobase, sugar molecule and a phosphate group. The combination of a nucleobase with a sugar forms a nucleoside.

Is thymidine the same as deoxythymidine?

Thymidine (symbol dT or dThd), also known as deoxythymidine, deoxyribosylthymine, or thymine deoxyriboside, is a pyrimidine deoxynucleoside.

How would you synthesise zidovudine from thymidine?

Zidovudine is 3′-azido-3′-deoxytimidine (36.1. 26), is synthesized from 1-(2′-deoxy-5′-O-trityl-β-d-lyxosyl)thymine, which is treated with methansulfonyl chloride in pyridine to make the corresponding mesylate 36.1.

What are the disadvantages of NRTIs?

CURRENT STRATEGIES TO IMPROVE NRTIS EFFICACY The main drawbacks of NRTIs as ART, are lifelong requirement, daily dosing, pill fatigue, patient non-adherence and toxicities or resistance.

How is Q151M related to resistance to NRTIs?

When Q151M is accompanied by mutations at codons 62, 75, 77 and 116, the resulting Q151M complex confers high-level resistance (>10-fold increase) to the aforementioned NRTIs (ZDV, ddI, d4T and ABC), as well as to 3TC. In addition, the Q151M complex is associated with decreased susceptibility to tenofovir (TDF) (2- to 5-fold decrease).

How does NRTI affect the activity of RT?

NRTI-associated mutations may affect the phosphorolytic activity of RT, in some cases overcoming chain termination in a mechanism called `primer unblocking’.

How are Tams used to reduce NRTI susceptibility?

TAMs are non-polymorphic mutations selected by the thymidine analogs AZT and d4T. They reduce NRTI susceptibility by facilitating primer unblocking (aka nucleotide excision, pyrophosphorolysis) ( 87, 88, 89, 90, 91, 92, 93 ).

How are reverse transcriptases able to resist NRTI binding?

Mechanisms of NRTI resistance. One mechanism for resistance to NRTIs is discrimination, whereby the reverse transcriptase (RT) enzyme is able to avoid binding of the NRTI, while retaining the ability to recognise the analogous natural deoxynucleoside triphosphate (dNTP) substrate.

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