How does HIV become resistant to AZT?
Human immunodeficiency virus (HIV-1) develops resistance to 3′-azido-2′,3′-deoxythymidine (AZT, zidovudine) by acquiring mutations in reverse transcriptase that enhance the ATP-mediated excision of AZT monophosphate from the 3′ end of the primer.
What does high genetic barrier to resistance mean?
A high genetic barrier to resistance allows a medication to bind itself tightly to the virus and keeps working even if the virus has changed.
What does K103N describe?
K103N Mutation. Virologic Failure while Taking Rilpivirine. Etravirine Resistance. Darunavir Resistance. Darunavir Dosing with Prior Virologic Failure.
What causes virus resistance?
Biological basis of resistance This phenotype is determined by specific mutations in the viral genome (the genotype), which leads to alterations in the viral target protein (for example, HIV reverse transcriptase) or the viral drug activator (for example, herpes simplex thymidine kinase).
What causes a virus to become resistant?
A resistance mutation is a mutation in a virus gene that allows the virus to become resistant to treatment with a particular antiviral drug. The term was first used in the management of HIV, the first virus in which genome sequencing was routinely used to look for drug resistance.
What does low barrier to resistance mean?
A genetic barrier to resistance can be defined basically as the number of mutations required to confer resistance. For instance, NNRTIs have a low genetic barrier as a single mutation can cause resistance to most agents, whereas PIs have a high genetic barrier as multiple mutations are required.
What kind of drug resistance does the K65R mutation cause?
This is the case when the K65R mutation arises in reverse transcriptase, which confers in-vivo resistance to abacavir, didanosine, lamivudine and tenofovir [1].
Is the K65R mutation related to tenofovir?
The K65R mutation can result from tenofovir DF, abacavir, stavudine, zalcitabine or didanosine therapy. From in vitro phenotypic analysis, the K65R mutation shows no cross-resistance to zidovudine, but low-level resistance to tenofovir and the other NRTIs.
Is the K65R mutation associated with didanosine use?
The K65R mutation has been reported to be associated with the use of abacavir, didanosine and tenofovir. With the advent of tenofovir we have assessed the change in the prevalence of this mutation. The prevalence of the K65R mutation remains low, but has significantly increased over a 2-year period.
Can a K65R mutation abrogate NRTI activity?
K65R + M184V/I appear sufficient to abrogate the NRTI activity of a regimen comprising ABC, TDF, or d4T plus a cytosine analog suggesting that despite the relatively low-levels of reduced susceptibility associated with K65R, this mutation is highly clinically relevant. K65R reduces 3TC and FTC susceptibility about 5 to 10-fold ( 3, 64 ).