Nnrti mutations. Medical search. Frequent questions

OBJECTIVE: To determine drug resistance mutation (DRM) patterns in a large cohort of patients failing nonnucleoside reverse transcriptase inhibitor (NNRTI)-based first-line antiretroviral therapy regimens in programs without routine viral load (VL) monitoring and to examine intersubtype differences in DRMs. (ox.ac.uk)
The patient with VF had no known nonnucleoside reverse transcriptase inhibitor (NNRTI) mutation at baseline and showed no acquired mutations in a subsequent genotypic test. (natap.org)
Antiretroviral therapy (ART) was initiated, consisting of the nucleotide/nucleoside reverse transcriptase inhibitors (NRTIs) tenofovir disoproxil fumarate (TDF) and lamivudine (3TC), in combination with the nonnucleoside reverse transcriptase inhibitor (NNRTI) doravirine (DOR). (medscape.com)
L. Marije Hofstra, MD, of the department of medical microbiology at the University Medical Center Utrecht, the Netherlands, and colleagues discovered that the increase in resistance is due to a rise in the nonnucleoside reverse transcriptase inhibitor (NNRTI) mutation K103N. (krisp.org.za)

HIV Drug Resistance Mutations in Non-B Subtypes After Prolonged Virological Failure on NNRTI-Based First-Line Regimens in Sub-Saharan Africa. (ox.ac.uk)
DOR is a novel NNRTI recommended for the treatment of both treatment-naïve and virologically suppressed PLWHIV.2 In our real-life scenario, DOR-based regimens demonstrated optimal tolerability and safety in the short-term. (natap.org)
Avoid INSTI-based regimens, unless an INSTI genotype shows no resistance mutations. (hiv.gov)
Avoid NNRTI-based regimens and DTG/3TC. (hiv.gov)
There was no evidence of differences between 3NRTI and 2NRTI+NNRTI long-term maintenance regimens in terms of clinical outcomes or CD4, but medium-term virological suppression was poorer with 3NRTI, supporting 2NRTI+NNRTI becoming the WHO-recommended first-line regimen for children as of 2013. (prolekare.cz)
The mutation has a detrimental effect against Sustiva (efavirenz, Bristol-Myers Squibb) and nevirapine, which are commonly used in first-line combination ART (cART) regimens in highly endemic countries. (krisp.org.za)
Those infected with a K103N strain were more often men who have sex with men and were more likely to experience virologic failure with NNRTI-based regimens. (krisp.org.za)
The individuals were enrolled in a clinical trial for people initiating HIV treatment to compare two drug regimens: efavirenz, an NNRTI and prior first-line therapy in the region, and dolutegravir. (ahri.org)

An open-label, multi-centre, randomised, switch study to evaluate the virological efficacy over 96 weeks of 2-drug therapy with DTG+RPV FDC in antiretroviral treatment-experienced HIV-1 infected subjects virologically suppressed with NNRTIs resistance mutation K103N. (clinicaltrialsregister.eu)
Étude switch ouverte, multicentrique, randomisée, afin d'évaluer l'efficacité virologique sur 96 semaines d'une bithérapie par association à dose fixe de DTG/RPV chez des patients infectés par le VIH-1, prétraités par des antirétroviraux, virologiquement supprimés, porteurs de la mutation K103N de résistance aux INNTI. (clinicaltrialsregister.eu)
The effect of switching to Dolutegravir and Rilpivirine combination therapy in patients with HIV-1 and the K103N mutation. (clinicaltrialsregister.eu)
Five (15.2%) patients presented a resistance mutation to NNRTIs at baseline: 3 had the E138A mutation, one had the K103N mutation, and, most notably, one patient presented the Y188L mutation in a previous genotypic analysis. (natap.org)
According to the researchers, all NNRTI resistance was due to the K103N mutation. (krisp.org.za)
An additional analysis of 28 participants who experienced treatment failure showed that 54% of participants had virus with a K103N mutation. (krisp.org.za)
The common NRTI mutations were M184VI and K65R, while NNRTI mutations were Y181CFGVY, K103N, A98AG, E138GQ and G190AGS. (actamedindones.org)

NNRTIs), a single mutation may be associated with a high level of resistance to drugs from that same class. (canada.ca)
Data from patients with previous resistance mutations to NNRTIs are particularly reassuring because none of them experienced any viral blip. (natap.org)
NNRTIs have a reputation for rapidly eliciting resistance due to mutations of the amino acids surrounding the NNRTIs' binding site. (i-sis.org.uk)
In contrast to the disappointing cross-resistance news with 1592, DuPont-Merck's new non-nucleoside reverse transcriptase inhibitor (NNRTI) DMP-266 (now with the generic name "efavirenz" and trade name "Sustiva"), seems to be active against the most common resistance mutation (Y181) associated with use of nevirapine and delavirdine, the two commercially available NNRTIs. (treatmentactiongroup.org)
Resistance of NNRTIs occurs through mutations of the reverse transcriptase gene in the viral genome. (antimicrobe.org)
However, the HIV-1 RT:7 structure reveals novel design features such as (1) interactions with the conserved Tyr183 from the YMDD-motif and (2) a possible way for an NNRTI to reach the polymerase active site that may be exploited in designing new NNRTIs. (neb.com)

In 2012, WHO reported that 60% and 67% of adults and children in sub-Saharan Africa failing first-line ART at 12 months had NRTI and NNRTI resistance, respectively [ 6 ]. (prolekare.cz)
Primary mutations associated with NRTI and NNRTI resistance were detected among 3% and 4% of treatment-naïve strains, respectively. (biomedcentral.com)
Primary mutations associated with NRTI and NNRTI resistance were detected in 1.6% and 11.5% of women who had received sdNVP, respectively. (biomedcentral.com)

HIV-1 sequences had been scored for medication level of resistance mutations using Stanford HIVdb and WHO 2009 mutation recommendations. (iwap2018.com)
This can be because of residual efficacy from the antiretroviral medications (specifically LPV/r) specifically at elevated plasma amounts [19] as well INCB024360 IC50 as the decreased fitness (crippling impact) of some level of resistance mutations such as for example M184V plus some PI level of resistance mutations. (biosemiotics2013.org)
Non-suppressive antiretroviral therapy may over time compromise potential therapy choices through the deposition of level of resistance mutations despite intermediate-term immunological and scientific benefits. (biosemiotics2013.org)

The prevalence of mutations associated with antiretroviral drug resistance in protease (PR) and reverse transcriptase (RT) regions among antiretroviral treatment-naïve HIV-1 infected pregnant women was investigated in Bukoba (Kagera) and Moshi (Kilimanjaro) municipalities, Tanzania, between September and December 2005. (biomedcentral.com)
Compilation and prevalence of mutations associated with resistance to non-nucleoside reverse transcriptase inhibitor. (actamedindones.org)

3 patients in the simplified group and 5 in the non-simplified group experienced virologic failure, however no emergence of new resistance mutations was observed. (aahivm.org)

CONCLUSIONS: Non-B subtypes differ in DRMs at first-line failure, which impacts on residual nucleoside reverse transcriptase inhibitor and NNRTI susceptibility. (ox.ac.uk)
Calanolide A is an experimental non-nucleoside reverse transcriptase inhibitor (NNRTI). (wikipedia.org)
3'-deoxy-3'-fluorothymidine, a drug briefly tested in the 1980's, has been dusted off and retested in a cohort of patients with multiple nucleoside analog mutations. (natap.org)
As reported by Vincent Calvez, due to in vitro activity against multinucleoside resistant strains, MIV-310 7.5 mg qd was added to the therapy of 15 patients with >2 nucleoside analog mutations, and median 3.93 log copies HIV RNA. (natap.org)
Once again, neither group included a non-nucleoside reverse transcriptase inhibitor (NNRTI) in their list of recommended combinations. (positivelyaware.com)
In a systematic review of 30 studies from low-income settings in 2011 [ 5 ], 80% and 88% of children failing first-line ART had 1 or more International AIDS Society (IAS)-USA major nucleoside reverse transcriptase inhibitor (NRTI) and non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance-associated mutations, respectively. (prolekare.cz)
NNRTI na ve patients with prior nucleoside analogue reverse transcriptase inhibitor (NRTI) exposure, who have isolates with resistance mutations and phenotypic resistance to NRTIs, appear more likely to have hypersusceptibility to the NNRTI class of drugs. (antimicrobe.org)
In case of adults, this includes patients on a first-line, non-nucleoside reverse transcriptase (NNRTI)-based regimen, or on a second-line, protease inhibitor (PI)-based regimen, and in case of children, this includes patients on a first-line PI-based regimen. (sun.ac.za)
Although more than 25 antiretroviral medications are available from 6 major classes, an ART regimen for treatment-naive patients generally consists of 2 nucleoside reverse transcriptase inhibitors (NRTIs) in combination with a third active ART drug from 1 of 3 drug classes: an integrase strand transfer inhibitor (INSTI), a non-nucleoside reverse transcriptase inhibitor (NNRTI), or a protease inhibitor (PI) with a pharmacologic enhancer (ie, cobicistat or ritonavir). (medscape.com)
however, TSAO compounds invoke non-nucleoside RT inhibitor (NNRTI) resistance mutations. (neb.com)
Patients with drug-resistant virus who are failing an initial regimen that includes a first-line nucleoside/nucleotide reverse transcriptase inhibitor (NRTI) backbone plus a non-nucleoside reverse transcriptase inhibitor (NNRTI), an integrase strand transfer inhibitor (INSTI), or a pharmacologically boosted protease inhibitor (PI) are likely to achieve viral suppression with their subsequent regimen. (medilib.ir)
HIV treatment usually consists of a cocktail of drugs that includes a type of drug known as a non-nucleoside reverse-transcriptase inhibitor (NNRTI). (ahri.org)

No integrase strand inhibitor (INSTI) resistance-associated mutations were reported. (jnj.com)

A drug-resistant HIV strain is one which is less susceptible to the effects of one or more anti-HIV drugs because of an accumulation of HIV mutations in its genotype. (aidsmap.com)
Baseline genotype testing reveals no HIV drug-resistant mutations. (medscape.com)
Multiple, linked human immunodeficiency virus type 1 drug resistance mutations in treatment-experienced patients are missed by standard genotype analysis. (scienceopen.com)
To investigate the extent to which drug resistance mutations are missed by standard genotyping methods, we analyzed the same plasma samples from 26 patients with suspected multidrug-resistant human immunodeficiency virus type 1 by using a newly developed single-genome sequencing technique and compared it to standard genotype analysis. (scienceopen.com)

The researchers say it is not clear why efavirenz-resistant mutations should affect susceptibility of dolutegravir, though one hypothesis is that integrase inhibitors such as dolutegravir push the virus to replicate and mutate faster, in turn developing resistance to the new drug in an evolutionary arms race. (ahri.org)

Drug resistance largely results from changes (mutations) in the genetic material that code for these enzymes, rendering ART less effective. (canada.ca)
The HIV virus is constantly changing, and mutations in the virus's genetic material occur on a daily basis. (canada.ca)
Genotypic tests identify mutations in the viral genetic material through sequencing the viral genes of interest. (canada.ca)
Antimicrobial resistance occurs through different mechanisms, which include spontaneous (natural) genetic mutations and horizontal transfer of resistant genes through deoxyribonucleic acid (DNA). (who.int)
Before antiretroviral drugs become more widely available, it is important to characterize baseline naturally occurring genetic mutations and polymorphisms associated with antiretroviral drug resistance among circulating HIV-1 subtypes. (biomedcentral.com)
Cystic fibrosis is a genetic disease caused by mutations in the CFTR gene. (emerginginvestigators.org)
If strengthened surveillance would show that these NNRTI-resistant viruses are more widespread in the region, a change of the current first-line NNRTI-based regimen to a regimen with a higher genetic barrier to resistance should be strongly considered, despite its major implications for resources and logistics. (krisp.org.za)
As HIV copies itself and replicates, it can develop errors, or 'mutations', in its genetic code (its RNA). (ahri.org)
In a study published today in Nature Communications , an international team of researchers from South Africa, the UK and the USA examined the genetic code of HIV to determine if drug resistance mutations in 874 volunteers living with HIV affected their treatment success. (ahri.org)

DESIGN: Sequences from 787 adults/adolescents who failed an NNRTI-based first-line regimen in 13 clinics in Uganda, Kenya, Zimbabwe, and Malawi were analyzed. (ox.ac.uk)
However, our data demonstrate that in a setting without adequate surveillance, the prevalence of infections with NNRTI resistant HIV can increase to worrisome levels, compromising the efficacy of the standard first-line NNRTI-based regimen. (krisp.org.za)
If a patient is infected with an NNRTI-resistant strain, they are at a two- to three-fold increased risk of the drug regimen failing. (ahri.org)

In the simplification group, 75% had anticipated high-level NRTI resistance, 78.6% had anticipated high-level NNRTI resistance, 7.1% had anticipated DRV-specific mutations, and 0 had anticipated high-level INSTI resistance. (aahivm.org)
Transmitted mutations conferring NNRTI and NRTI resistance are more likely than mutations associated with PI or INSTI resistance. (hiv.gov)

By comparing the generated sequences with databases containing resistance-conferring mutations, the presence or absence of drug resistance can be determined. (canada.ca)
Mutations conferring resistance to antiretroviral drugs are based on comparing gene sequences with corresponding consensus sequences of HIV-1 subtype B that represents only 10% of the AIDS pandemic. (biomedcentral.com)
and that evidence of strong immunologic selection can be seen in Env and overlapping Rev sequences based on nonrandom accumulation of nonsynonymous mutations. (scienceopen.com)

However, unexpectedly, the same pattern was true for individuals taking dolutegravir-based treatments: 66% of those with efavirenz resistance mutations remained suppressed over 96-weeeks compared to 84% of those without the mutations. (ahri.org)

Presence of drug resistance mutations by location (A) and by risk factor (B) for 1,397 patients with HIV, Germany, 2001-2018. (cdc.gov)
Baseline characteristics were generally similar between patients who underwent simplification (median baseline GSS 3) and those who did not (median baseline GSS 2.5), although there were more patients with darunavir-specific mutations in the non-simplified group. (aahivm.org)
Furthermore, a subset of samples showed that patients failing ART for extended periods of time had HIV-1 strains harboring drug resistance mutations. (beds.ac.uk)
Abstract: Impact of HIV type 1 subtype on drug resistance mutations in Nigerian patients failing first-line therapy. (actamedindones.org)
Results after detecting PI resistance Patients who continued on an LPV/r routine had a better virological INCB024360 IC50 response than those switched to an NNRTI routine. (biosemiotics2013.org)

With the sequencing method, analysis of gene mutations encoded HIV drug resistance. (actamedindones.org)

WISARD: acronym of SWItch Study mutAtion Rilpivirine Dolutegravir. (clinicaltrialsregister.eu)

Most mutations do not result in the development of drug resistance, as they are lethal, reduce fitness, or even if not affecting viral growth, occur at sites that are not targeted by ART. (canada.ca)
However, under conditions in which treatment does not completely inhibit viral replication, a virus with drug-resistant mutations may begin to thrive, resulting in treatment failure. (canada.ca)
Some of these mistakes, called mutations, can make HIV resistant to one or more ARV drug. (mtnstopshiv.org)
Drug-induced resistance was found in adults failing first-line NNRTI-based cART, with 83% having resistance to ≥1 drug. (sun.ac.za)
Viral supression allows for immunologic improvement (as measured by CD4 counts), prevents the selection of drug-resistance mutation, and decreases HIV transmission to others. (medscape.com)
Positions 1-350 of the RT and 1-99 of the PR genes were analyzed for mutations based on the Stanford University HIV Drug Resistance Database. (biomedcentral.com)
Based on the WHO HIV Drug Resistance Research Network Threshold of less than 5%, the baseline prevalence of primary mutations among treatment-naïve HIV-1 infected pregnant women in Kagera and Kilimanjaro regions was low. (biomedcentral.com)
however, the likelihood of virologic suppression depends upon the drugs used and number and types of drug-resistant mutations that are present. (medilib.ir)
While a drug may initially be able to supress or even kill the virus, certain mutations can allow the virus to develop resistance to its effects. (ahri.org)

Here, the authors employ homology modeling and molecular docking towards the identification of novel rilpivirine analogs that retain high binding affinity to clinically relevant rilpivirine-resistant mutations of the HIV reverse transcriptase enzyme. (emerginginvestigators.org)

Mutations in the HIV-1 genome are often associated with treatment failure as indicated by viral replication and elevated levels of virus in the blood. (biomedcentral.com)

None of the primary mutations associated with PI resistance was found. (biomedcentral.com)

Exposure to 810 induced mutations in the catalytic core of HIV integrase, resulting in 1.6-fold to 9-fold resistance. (natap.org)

The prevalence of transmitted ARVDR in adults was low, as was initial ARVDR in young children (mostly PMTCT-exposed), except for NNRTI resistance in children who had received NVP as part of PMTCT. (sun.ac.za)

Subtype G viruses also contained more RT cleavage site mutations. (ucl.ac.uk)

It is thus likely that cimetidine acts like an NNRTI and has the ability to treat HIV infection. (i-sis.org.uk)

More studies addressing the correlation between polymorphic mutations, antiretroviral resistance and clinical outcome are warranted in regions where non-B subtypes are prevalent. (biomedcentral.com)

Of the 365 individuals, 345 (95.1, 95% CI: 92.3-96.9) had VL below 1000 copies/mL and 19 (4.6%, 95% CI: 2.8-7.5) had HIVDR mutations. (who.int)

No mayor PI mutations were found. (actamedindones.org)

Detected NRTI resistance mutations Once major PI resistance was present as expected all children on lamivudine (3TC) experienced the M184V mutation. (biosemiotics2013.org)

AFRIKAANSE OPSOMMING: Inleiding: Sedert die begin van die Suid Afrikaanse publieke sektor antiretrovirale uitrol program in 2004 is die sukses van antiretrovirale kombinasie-behandeling (k-ARB) ervaar in terme van oorlewing, voorkoming van moeder na kind oordrag (VMKO) en lewenskwaliteit. (sun.ac.za)
The Order Relationship and Binary Operations for Shifting Mutations Let us begin with the definitions of relationships between and operations on the modes caused by sequence mutations. (top5binarybrokers.com)

Anatomy4

Organisms10

Diseases8

Chemicals and Drugs63

Analytical, Diagnostic and Therapeutic Techniques and Equipment34

Psychiatry and Psychology1

Phenomena and Processes87

Disciplines and Occupations1

Information Science4

Named Groups2

Health Care10

Nonnucleoside reverse4

Regimens8

K103N7

NNRTIs6

NRTI and NNRTI3

Level of resistance mutations3

Prevalence of mutations associated2

Virologic failure1

Nucleoside12

Inhibitor1

Genotype4

Susceptibility1

Genetic9

Regimen3

INSTI2

Sequences3

Efavirenz1

Patients5

Gene1

Dolutegravir1

Drug9

Reverse1

Failure1

Resistance was found1

Integrase1

Adults1

Viruses1

Infection1

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