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Non-Nucleoside Reverse Transcriptase Inhibitor

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1. Multicenter study of skin rashes and hepatotoxicity in antiretroviral-naïve HIV-positive patients receiving non-nucleoside reverse-transcriptase inhibitor plus nucleoside reverse-transcriptase inhibitors in Taiwan. Full Text available with Trip Pro

Multicenter study of skin rashes and hepatotoxicity in antiretroviral-naïve HIV-positive patients receiving non-nucleoside reverse-transcriptase inhibitor plus nucleoside reverse-transcriptase inhibitors in Taiwan. Two nucleos(t)ide reverse-transcriptase inhibitors (NRTIs) plus 1 non-NRTI (nNRTI) remain the preferred or alternative combination antiretroviral therapy (cART) for antiretroviral-naive HIV-positive patients in Taiwan. The three most commonly used nNRTIs are nevirapine (NVP

2017 PLoS ONE

2. Non-nucleoside reverse transcriptase inhibitor levels among HIV-exposed uninfected infants at the time of HIV PCR testing - findings from a tertiary healthcare facility in Pretoria, South Africa. Full Text available with Trip Pro

Non-nucleoside reverse transcriptase inhibitor levels among HIV-exposed uninfected infants at the time of HIV PCR testing - findings from a tertiary healthcare facility in Pretoria, South Africa. To date, very little programmatic data has been published regarding serial antiretroviral (ARV) levels in infants exposed to maternal treatment and/or infant prophylaxis during the first months of life. Such data provide the opportunity to describe the proportion of infants exposed to virologically

2019 Journal of the International AIDS Society

3. Non-nucleoside reverse transcriptase inhibitor efavirenz activates PXR to induce hypercholesterolemia and hepatic steatosis. (Abstract)

Non-nucleoside reverse transcriptase inhibitor efavirenz activates PXR to induce hypercholesterolemia and hepatic steatosis. The most prescribed non-nucleoside reverse transcriptase inhibitor, efavirenz, has been associated with elevated risk of dyslipidemia and hepatic steatosis in HIV-infected patients but the underlying mechanisms remain elusive. Herein, we investigated the role of pregnane X receptor (PXR) in mediating the adverse effects of efavirenz on lipid homeostasis.Cell-based

2019 Journal of Hepatology

4. A computational study for rational HIV-1 non-nucleoside reverse transcriptase inhibitor selection and the discovery of novel allosteric pockets for inhibitor design Full Text available with Trip Pro

A computational study for rational HIV-1 non-nucleoside reverse transcriptase inhibitor selection and the discovery of novel allosteric pockets for inhibitor design HIV drug resistant mutations that render the current Highly Active Anti-Retroviral Therapy (HAART) cocktail drugs ineffective are increasingly reported. To study the mechanisms of these mutations in conferring drug resistance, we computationally analyzed 14 reverse transcriptase (RT) structures of HIV-1 on the following parameters (...) : drug-binding pocket volume, allosteric effects caused by the mutations, and structural thermal stability. We constructed structural correlation-based networks of the mutant RT-drug complexes and the analyses support the use of efavirenz (EFZ) as the first-line drug, given that cross-resistance is least likely to develop from EFZ-resistant mutations. On the other hand, rilpivirine (RPV)-resistant mutations showed the highest cross-resistance to the other non-nucleoside RT inhibitors

2018 Bioscience reports

5. Combining New Non-Nucleoside Reverse Transcriptase Inhibitors (RTIs) with AZT Results in Strong Synergism against Multi-RTI-Resistant HIV-1 Strains Full Text available with Trip Pro

Combining New Non-Nucleoside Reverse Transcriptase Inhibitors (RTIs) with AZT Results in Strong Synergism against Multi-RTI-Resistant HIV-1 Strains Reverse transcriptase inhibitors (RTIs), including nucleoside RTIs (NRTIs) and non-nucleoside RTIs (NNRTIs), are critical antiretroviral drugs for the treatment of human immunodeficiency virus (HIV) infection. Emergence of multi-RTI resistance calls for the development of more potent therapeutics or regimens against RTI-resistant strains. Here, we

2018 Molecules : A Journal of Synthetic Chemistry and Natural Product Chemistry

6. Patterns of emergent resistance-associated mutations after initiation of non-nucleoside reverse-transcriptase inhibitor-containing antiretroviral regimens in Taiwan: a multicenter cohort study Full Text available with Trip Pro

Patterns of emergent resistance-associated mutations after initiation of non-nucleoside reverse-transcriptase inhibitor-containing antiretroviral regimens in Taiwan: a multicenter cohort study Increasing trends of resistance-associated mutations (RAMs) to non-nucleoside reverse-transcriptase inhibitors (nNRTIs) have raised concerns about the effectiveness of the regimens in the national HIV treatment programs in resource-limited countries. We aimed to retrospectively investigate the incidence (...) . Population sequencing was retrospectively performed to detect baseline and emergent RAMs. RAMs were interpreted using the International AIDS Society-USA 2016 mutations list.Seventy-one patients (6.2%) developed virological failure, which occurred in 14.8% (43/291), 3.9% (26/675), and 1.2% (2/172) of patients receiving 2 nucleoside reverse-transcriptase inhibitors (NRTIs) plus nevirapine, efavirenz, and rilpivirine, respectively. Among those, 53 (74.6%) had emergent RAMs identified, which included 43

2018 Infection and drug resistance

7. The structure of FIV reverse transcriptase and its implications for non-nucleoside inhibitor resistance Full Text available with Trip Pro

The structure of FIV reverse transcriptase and its implications for non-nucleoside inhibitor resistance Reverse transcriptase (RT) is the target for the majority of anti-HIV-1 drugs. As with all anti-AIDS treatments, continued success of RT inhibitors is persistently disrupted by the occurrence of resistance mutations. To explore latent resistance mechanisms potentially accessible to therapeutically challenged HIV-1 viruses, we examined RT from the related feline immunodeficiency virus (FIV (...) ). FIV closely parallels HIV-1 in its replication and pathogenicity, however, is resistant to all non-nucleoside inhibitors (NNRTI). The intrinsic resistance of FIV RT is particularly interesting since FIV harbors the Y181 and Y188 sensitivity residues absent in both HIV-2 and SIV. Unlike RT from HIV-2 or SIV, previous efforts have failed to make FIV RT susceptible to NNRTIs concluding that the structure or flexibility of the feline enzyme must be profoundly different. We report the first crystal

2018 PLoS pathogens

8. Indolylarylsulfones, a fascinating story of highly potent human immunodeficiency virus type 1 non-nucleoside reverse transcriptase inhibitors Full Text available with Trip Pro

Indolylarylsulfones, a fascinating story of highly potent human immunodeficiency virus type 1 non-nucleoside reverse transcriptase inhibitors Indolylarylsulfones are a potent class of human immunodeficiency virus type 1 non-nucleoside reverse transcriptase inhibitors. In this review, the structure activity relationship (SAR) studies to improve the profile of sulfone L-737,126 discovered by Merck AG have been analysed with focus on introduction of the 3',5'-dimethyl groups at the 3

2018 Antiviral chemistry & chemotherapy

9. Switching to the single-tablet regimen of elvitegravir, cobicistat, emtricitabine, and tenofovir DF from non-nucleoside reverse transcriptase inhibitor plus coformulated emtricitabine and tenofovir DF regimens: Week 96 results of STRATEGY-NNRTI. (Abstract)

Switching to the single-tablet regimen of elvitegravir, cobicistat, emtricitabine, and tenofovir DF from non-nucleoside reverse transcriptase inhibitor plus coformulated emtricitabine and tenofovir DF regimens: Week 96 results of STRATEGY-NNRTI. HIV-1-infected, virologically suppressed adults wanting to simplify or change their non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimens may benefit from switching to the single-tablet regimen of elvitegravir, cobicistat, emtricitabine

2018 HIV clinical trials Controlled trial quality: uncertain

10. Structural and Preclinical Studies of Computationally Designed Non-Nucleoside Reverse Transcriptase Inhibitors for Treating HIV infection Full Text available with Trip Pro

Structural and Preclinical Studies of Computationally Designed Non-Nucleoside Reverse Transcriptase Inhibitors for Treating HIV infection The clinical benefits of HIV-1 non-nucleoside reverse transcriptase (RT) inhibitors (NNRTIs) are hindered by their unsatisfactory pharmacokinetic (PK) properties along with the rapid development of drug-resistant variants. However, the clinical efficacy of these inhibitors can be improved by developing compounds with enhanced pharmacological profiles

2017 Molecular pharmacology

11. Etravirine and Rilpivirine Drug Resistance Among HIV-1 Subtype C Infected Children Failing Non-Nucleoside Reverse Transcriptase Inhibitor-Based Regimens in South India Full Text available with Trip Pro

Etravirine and Rilpivirine Drug Resistance Among HIV-1 Subtype C Infected Children Failing Non-Nucleoside Reverse Transcriptase Inhibitor-Based Regimens in South India We have analyzed reverse transcriptase (RT) region of HIV-1 pol gene from 97 HIV-infected children who were identified as failing first-line therapy that included first-generation non-nucleoside RT inhibitors (Nevirapine and Efavirenz) for at least 6 months. We found that 54% and 65% of the children had genotypically predicted (...) resistance to second-generation non-nucleoside RT inhibitors drugs Etravirine (ETR) and Rilpivirine, respectively. These cross-resistance mutations may compromise future NNRTI-based regimens, especially in resource-limited settings. To complement these investigations, we also analyzed the sequences in Stanford database, Monogram weighted score, and DUET weighted score algorithms for ETR susceptibility and found almost perfect agreement between the three algorithms in predicting ETR susceptibility from

2017 AIDS research and human retroviruses

12. Drug-like property-driven optimization of 4-substituted 1,5-diarylanilines as potent HIV-1 non-nucleoside reverse transcriptase inhibitors against rilpivirine-resistant mutant virus Full Text available with Trip Pro

Drug-like property-driven optimization of 4-substituted 1,5-diarylanilines as potent HIV-1 non-nucleoside reverse transcriptase inhibitors against rilpivirine-resistant mutant virus On the basis of our prior structure-activity relationship (SAR) results, our current lead optimization of 1,5-diarylanilines (DAANs) focused on the 4-substituent (R1) on the central phenyl ring as a modifiable position related simultaneously to improved drug resistance profiles and drug-like properties. Newly

2017 Bioorganic & medicinal chemistry letters

13. Non-Nucleoside Reverse Transcriptase Inhibitor

Non-Nucleoside Reverse Transcriptase Inhibitor Non-Nucleoside Reverse Transcriptase Inhibitor Toggle navigation Brain Head & Neck Chest Endocrine Abdomen Musculoskeletal Skin Infectious Disease Hematology & Oncology Cohorts Diagnostics Emergency Findings Procedures Prevention & Management Pharmacy Resuscitation Trauma Emergency Procedures Ultrasound Cardiovascular Emergencies Lung Emergencies Infectious Disease Pediatrics Neurologic Emergencies Skin Exposure Miscellaneous Abuse Cancer (...) Administration 4 Non-Nucleoside Reverse Transcriptase Inhibitor Non-Nucleoside Reverse Transcriptase Inhibitor Aka: Non-Nucleoside Reverse Transcriptase Inhibitor , NNRTI From Related Chapters II. Mechanism Bind directly to reverse transcriptase Prevents RNA conversion to DNA Completely different mechanism than III. Preparations: First Generation Delavirdine (Rescriptor) ( , EFV) ( , NVP) IV. Preparations: Second Generation ( ) Approved in treatment experienced patients Rilpivirine (Endurant) FDA approved

2018 FP Notebook

14. Malaria in HIV-Infected Children Receiving HIV Protease-Inhibitor- Compared with Non-Nucleoside Reverse Transcriptase Inhibitor-Based Antiretroviral Therapy, IMPAACT P1068s, Substudy to P1060. Full Text available with Trip Pro

Malaria in HIV-Infected Children Receiving HIV Protease-Inhibitor- Compared with Non-Nucleoside Reverse Transcriptase Inhibitor-Based Antiretroviral Therapy, IMPAACT P1068s, Substudy to P1060. HIV and malaria geographically overlap. HIV protease inhibitors kill malaria parasites in vitro and in vivo, but further evaluation in clinical studies is needed.Thirty-one children from Malawi aged 4-62 months were followed every 3 months and at intercurrent illness visits for ≤47 months (September 2009 (...) -December 2011). We compared malaria parasite carriage by blood smear microscopy (BS) and confirmed clinical malaria incidence (CCM, or positive BS with malaria symptoms) in children initiated on HIV antiretroviral therapy (ART) with zidovudine, lamivudine, and either nevirapine (NVP), a non-nucleoside reverse transcriptase inhibitor, or lopinavir-ritonavir (LPV-rtv), a protease inhibitor.We found an association between increased time to recurrent positive BS, but not CCM, when anti-malarial treatment

2016 PLoS ONE Controlled trial quality: uncertain

15. The choice between a ritonavir-boosted protease inhibitor- and a non-nucleoside reverse transcriptase inhibitor-based regimen for initiation of antiretroviral treatment – results from an observational study in Germany Full Text available with Trip Pro

The choice between a ritonavir-boosted protease inhibitor- and a non-nucleoside reverse transcriptase inhibitor-based regimen for initiation of antiretroviral treatment – results from an observational study in Germany This study aims at identifying predictors of the treatment decision of German physicians with regard to a non-nucleoside reverse transcriptase inhibitor (NNRTI) or a ritonavir-boosted protease inhibitor (PI/r) -based initial treatment regimen.The study is based on a sub analysis

2016 Journal of pharmaceutical policy and practice

16. Physiological Mg2+ Conditions Significantly Alter the Inhibition of HIV-1 and HIV-2 Reverse Transcriptases by Nucleoside and Non-Nucleoside Inhibitors in Vitro Full Text available with Trip Pro

Physiological Mg2+ Conditions Significantly Alter the Inhibition of HIV-1 and HIV-2 Reverse Transcriptases by Nucleoside and Non-Nucleoside Inhibitors in Vitro Reverse transcriptases (RTs) are typically assayed in vitro with 5-10 mM Mg2+, whereas the free Mg2+ concentration in cells is much lower. Artificially high Mg2+ concentrations used in vitro can misrepresent different properties of human immunodeficiency virus (HIV) RT, including fidelity, catalysis, pausing, and RNase H activity. Here (...) , we analyzed nucleoside (NRTIs) and non-nucleoside RT inhibitors (NNRTIs) in primer extension assays at different concentrations of free Mg2+. At low concentrations of Mg2+, NRTIs and dideoxynucleotides (AZTTP, ddCTP, ddGTP, and 3TCTP) inhibited HIV-1 and HIV-2 RT synthesis less efficiently than they did with large amounts of Mg2+, whereas inhibition by the "translocation-defective RT inhibitor" EFdA (4'-ethynyl-2-fluoro-2'-deoxyadenosine) was unaffected by Mg2+ concentrations. Steady-state

2016 Biochemistry

17. Long-term effectiveness of initiating non-nucleoside reverse transcriptase inhibitor- versus ritonavir-boosted protease inhibitor-based antiretroviral therapy: implications for first-line therapy choice in resource-limited settings. Full Text available with Trip Pro

Long-term effectiveness of initiating non-nucleoside reverse transcriptase inhibitor- versus ritonavir-boosted protease inhibitor-based antiretroviral therapy: implications for first-line therapy choice in resource-limited settings. In many resource-limited settings, combination antiretroviral therapy (cART) failure is diagnosed clinically or immunologically. As such, there is a high likelihood that patients may stay on a virologically failing regimen for a substantial period of time. Here, we (...) compared the long-term impact of initiating non-nucleoside reverse transcriptase inhibitor (NNRTI)- versus boosted protease inhibitor (bPI)-based cART in British Columbia (BC), Canada.We followed prospectively 3925 ART-naïve patients who started NNRTIs (N=1963, 50%) or bPIs (N=1962; 50%) from 1 January 2000 until 30 June 2013 in BC. At six months, we assessed whether patients virologically failed therapy (a plasma viral load (pVL) >50 copies/mL), and we stratified them based on the pVL at the time

2016 Journal of the International AIDS Society

18. Dolutegravir versus ritonavir-boosted lopinavir both with dual nucleoside reverse transcriptase inhibitor therapy in adults with HIV-1 infection in whom first-line therapy has failed (DAWNING): an open-label, non-inferiority, phase 3b trial. (Abstract)

inhibitors (NRTIs) in adults in whom previous first-line antiretroviral therapy with a non-nucleoside reverse transcriptase inhibitor (NNRTI) plus two NRTIs has failed.DAWNING is a phase 3b, open-label, parallel-group, non-inferiority, active-controlled trial done at 58 sites in 13 countries. Eligible adults were aged at least 18 years and, during at least 6 months of treatment with a first-line treatment containing an NNRTI and two NRTIs, had virological failure (confirmed HIV-1 RNA ≥400 copies per mL (...) Dolutegravir versus ritonavir-boosted lopinavir both with dual nucleoside reverse transcriptase inhibitor therapy in adults with HIV-1 infection in whom first-line therapy has failed (DAWNING): an open-label, non-inferiority, phase 3b trial. Doubts exist regarding optimal second-line treatment options for HIV-1-infected patients in resource-limited settings. We assessed safety and efficacy of dolutegravir compared with ritonavir-boosted lopinavir, plus two nucleoside reverse transcriptase

2019 Lancet infectious diseases Controlled trial quality: predicted high

19. Non-Nucleoside Reverse Transcriptase Inhibitor-Based Antiretroviral Therapy in Perinatally HIV-Infected, Treatment-Naïve Adolescents in Asia. Full Text available with Trip Pro

Non-Nucleoside Reverse Transcriptase Inhibitor-Based Antiretroviral Therapy in Perinatally HIV-Infected, Treatment-Naïve Adolescents in Asia. About a third of untreated, perinatally HIV-infected children reach adolescence. We evaluated the durability and effectiveness of non-nucleoside reverse-transcriptase inhibitor (NNRTI)-based antiretroviral therapy (ART) in this population.Data from perinatally HIV-infected, antiretroviral-naïve patients initiated on NNRTI-based ART aged 10-19 years who

2016 The Journal of Adolescent Health

20. Incidence and risk factors for neuropsychiatric events among Ghanaian HIV patients on long-term non-nucleoside reverse transcriptase inhibitor-based therapy Full Text available with Trip Pro

Incidence and risk factors for neuropsychiatric events among Ghanaian HIV patients on long-term non-nucleoside reverse transcriptase inhibitor-based therapy Non-nucleoside reverse transcriptase inhibitor (NNRTI)-based antiretroviral therapy (ART) is associated with neuropsychiatric toxicity. Little is known about the risk of short- and long-term neuropsychiatric toxicity in sub-Saharan Africa, where NNRTIs are widely used in first-line combination ART. This observational study assessed the risk

2016 eNeurologicalSci

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