What are thymidine analogue mutations?
Thymidine Analog Mutations (TAMs) 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).
What is M184V mutation?
“M184V” is the shorthand for methionine replacing valine at position 184 in reverse transcriptase. It is by far the most commonly encountered nucleoside reverse transcriptase inhibitor (NRTI) mutation after failure with regimens containing lamivudine (3TC) or emtricitabine (FTC).
What is the signature mutation associated with resistance to emtricitabine and lamivudine?
The infrequent development of K65R in drug-naive and treatment-experienced patients is due to impaired K65R replicative capacity and fitness constraints imposed by K65R and M184V – associated with resistance to lamivudine (3TC) and emtricitabine (FTC) and regimen potency (e.g., TDF–FTC).
How does thymidine analog work?
Replicating cells undergo DNA synthesis in the highly regulated, S-phase of the cell cycle. Analogues of the pyrimidine deoxynucleoside thymidine may be inserted into replicating DNA, effectively tagging dividing cells allowing their characterisation.
What are NNRTI and Nrti?
So NRTIs are like another zip giving the zipper another track to follow. NNRTIs work by sitting in a binding site in the virus structure and this is a bit like having an object that blocks the teeth of the zipper, so the zipper cannot get past the block.
What does NNRTI and Nrti mean?
Nucleoside analog reverse-transcriptase inhibitors (NARTIs or NRTIs) Nucleotide analog reverse-transcriptase inhibitors (NtARTIs or NtRTIs) Non-nucleoside reverse-transcriptase inhibitors (NNRTIs) Nucleoside reverse transcriptase translocation inhibitor (NRTTIs).
How is emtricitabine related to lamivudine?
Emtricitabine (FTC, Emtriva) and lamivudine (3TC, Epivir) belong to the nucleoside reverse transcriptase inhibitor (NRTI) class of antiretrovirals. They are a mainstay of first-line ART regimens and are considered equivalent and interchangeable in treatment guidelines.
Why do NRTIs have side effects?
Answer. Adverse effects of the NRTI class include mitochondrial toxicities (e.g., lactic acidosis, pancreatitis, peripheral neuropathy, hepatic steatosis, lipoatrophy). Mitochondrial toxicities are due to NRTI binding to human mitochondrial DNA polymerase-γ enzyme, impairing cellular respiration.
What are the side effects of NRTIs?
NRTIs and Side Effects
- Nausea.
- Dizziness.
- Tiredness.
- Stomach problems.
- Headache.
- Diarrhea.
- Trouble sleeping.
Is there another name for raltegravir?
Raltegravir (brand names: Isentress and Isentress HD) is a prescription medicine approved by the U.S. Food and Drug Administration (FDA) for the treatment of HIV infection in adults and children.
What is raltegravir used for?
Raltegravir is used along with other medications to treat human immunodeficiency virus (HIV) infection in adults and children who weigh at least 4.5 lbs (2 kg). Raltegravir is in a class of medications called HIV integrase inhibitors. It works by decreasing the amount of HIV in the blood.
What are examples of NNRTI?
Following are the FDA-approved individual NNRTIs that are currently part of antiretroviral therapy for HIV infection; common side effects are listed.
- Delavirdine (Rescriptor)
- Efavirenz (Sustiva)
- Etravirine (Intelence)
- Nevirapine (Viramune, Viramune XR)
- Rilpivirine (Edurant)
- Doravirine (Pifeltro)
How do NRTIs and NNRTIs work?
NNRTIs work by binding to the HIV enzyme called reverse transcriptase, which is essential to the viral replication process, and therefore blocking HIV from making copies of itself. Dapivirine is an example of an NNRTI. NRTIs work by mimicking nucleotides that are the building blocks of viral DNA.
Can lamivudine replace emtricitabine?
The findings of this systematic review suggest that lamivudine and emtricitabine are clinically equivalent.
How does HIV-1 develop thymidine analogue mutations (TAMs)?
Background: Studies have suggested that HIV-1 may develop thymidine analogue mutations (TAMs) by one of two distinct pathways – the TAM1 pathway (including mutations 41L, 210W and 215Y) or the TAM2 pathway (including mutations 67N, 70R and 219E/Q) – under the pressure of a not fully suppressive thymidine-analogue-containing regimen.
What is an example of a thymidine analog?
Examples of such analogues are 5-bromo-2′-deoxyuridine (BrdU), 5-Chloro-2′-deoxyuridine (CldU), 5-Iodo-2′-deoxyuridine (IdU), and 5-ethynyl-2′-deoxyuridine (EdU). However, the presence of these thymidine analogues can lead to mutations, DNA damage and cell-cycle delay [8].
Is thymidine analogue mutation clustering a real phenomenon?
Thymidine analogue mutation profiles: factors associated with acquiring specific profiles and their impact on the virological response to therapy This study provides evidence that the suggested TAM clustering is a real phenomenon and that it may be driven by which thymidine analogue the patients has used.
Can we use thymidine analogs in fission yeast cells for cell-cycle analysis?
In this study we have improved and refined the use of thymidine analogues to allow their detectable labelling in fission yeast cells with a minimum of cell-cycle perturbation. We have addressed which analogue is best for cell-cycle analyses, how sensitive the method is and how to double-label the DNA with two different analogues.