scholarly journals Prevalence of etravirine (TMC-125) resistance mutations in HIV-infected patients with prior experience of non-nucleoside reverse transcriptase inhibitors

2007 ◽  
Vol 60 (6) ◽  
pp. 1409-1410 ◽  
Author(s):  
E. Poveda ◽  
C. Garrido ◽  
C. de Mendoza ◽  
A. Corral ◽  
J. Cobo ◽  
...  
Keyword(s):  
Reverse Transcriptase ◽  
Prior Experience ◽  
Resistance Mutations ◽  
Reverse Transcriptase Inhibitors ◽  
Nucleoside Reverse Transcriptase Inhibitors

scholarly journals HIV Drug Resistance Mutations in Patients with HIV and HIV-TB Coinfection After Failure of First-Line Therapy: A Prevalence Study in a Resource-Limited Setting

2019 ◽  
Vol 18 ◽  
pp. 232595821984906
Author(s):  
Nawaid Hussain Khan ◽  
Mikashmi Kohli ◽  
Kartik Gupta ◽  
Bimal Kumar Das ◽  
Ravindra Mohan Pandey ◽  
...  
Keyword(s):  
Reverse Transcriptase ◽  
Drug Resistant ◽  
Resistance Mutations ◽  
Reverse Transcriptase Inhibitors ◽  
Nucleoside Reverse Transcriptase Inhibitors ◽  
First Line Therapy ◽  
Resource Limited ◽  
High Prevalence ◽  
Hiv 1 ◽  
Limited Setting

Introduction: The present study aimed to report the prevalent HIV-1 drug-resistant mutations in patients with HIV-1 alone and tuberculosis (TB) coinfection alone to improve our understanding of the mutation patterns and aid treatment decisions. Methods: Patients with HIV-1 and HIV-TB on treatment for more than 1 year with suspected failure were recruited. Sequencing of protease and two-thirds of the region of reverse transcriptase gene was done for drug-resistant mutations. Results: In the HIV-TB group (n = 25), 88%, 92%, and 12% had mutations to nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), and protease inhibitors (PIs), respectively. In the HIV-alone group (n = 25), 84%, 100%, and 4% had mutations to NRTIs, NNRTIs, and PIs, respectively. M184V, M41L, D67N, G190A, A98G, and K103N were the most common mutations seen. Conclusion: There is a high prevalence of drug-resistant mutations in HIV and HIV-TB coinfected patients.

New resistance mutations to nucleoside reverse transcriptase inhibitors at codon 184 of HIV-1 reverse transcriptase (M184L and M184T)

2018 ◽  
Vol 93 (1) ◽  
pp. 50-59 ◽  
Author(s):  
Lydia Pouga ◽  
Maria Mercedes Santoro ◽  
Charlotte Charpentier ◽  
Domenico Di Carlo ◽  
Isabella Romeo ◽  
...  
Keyword(s):  
Reverse Transcriptase ◽  
Resistance Mutations ◽  
Reverse Transcriptase Inhibitors ◽  
Nucleoside Reverse Transcriptase Inhibitors ◽  
Hiv 1

scholarly journals Barcoding analysis of HIV drug resistance mutations using Oxford Nanopore MinION (ONT) sequencing

2017 ◽  
Author(s):  
Claudia Gonzalez ◽  
Jessica Gondola ◽  
Alma Y Ortiz ◽  
Juan M Castillo ◽  
Juan M Pascale ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Reverse Transcriptase ◽  
Treatment Resistance ◽  
Resistance Mutations ◽  
Reverse Transcriptase Inhibitors ◽  
Nucleoside Reverse Transcriptase Inhibitors ◽  
Hiv Drug Resistance ◽  
Drug Resistance Mutations ◽  
Oxford Nanopore ◽  
Pre Treatment

ABSTRACTDetermination of HIV drug resistance (HIVDR) is becoming an integral baseline HIV evaluation for newly infected subjects, as the level of pre-treatment resistance is increasing worldwide. Until now, the gold standard for monitoring ART mutations is the Sanger sequencing method, however, next-generation sequencing technologies (NGS) because high-throughput capability, are gaining attention as a method for detection of HIVDR. In the present work, we evaluated the use of the Oxford Nanopore Technologies (ONT) MinION as an alternative method for detection of drug resistance mutations in pre-treatment HIV positive subjects.We evaluate 36 samples taken during November 2016 from treatment naïve subjects with age greater than 18 years old, who went to the lab for their first HIV monitoring. To evaluate the agreement between Sanger and MinION generated sequences, we aligned the sequences (∼1200bp) with muscle v. 3.8.31. Then we counted the differences and calculated the p-distance of the obtained sequences, comparing paired sequences and grouping Sanger and MinION obtained sequences. The percentage of similarity among each sequence was also evaluated.All samples were submitted to the Standford University HIV drug resistance database (HIVdb version 8.4). Then we compared the resistance predictions obtained from the sequences generated by Sanger and MinION methods.Results: The median of available pores was 1314 for the first run, 1215 for the second run, and 536 for the third run. After 3 hours with SQK-NSK007 a total of 18803 2D reads were base-called and in 16577 reads (88%) a barcode was detected.Comparing the nucleotide differences of each sample, we observed that 23 (74%) samples had identical sequence, for the other samples the percentage of identity among each analyzed sequence was greater than 95%. A good positive predictive value (100%) in the estimation of drug resistance mutations in the groups of protease inhibitors (PI), nucleoside reverse transcriptase inhibitors (NRTIs), and non-nucleoside reverse transcriptase inhibitors (NNRTIs).We present an approach for the analysis of HIV reads generated with MinION ONT, further studies are guaranteed before the application of this methodology in clinical settings to assess its suitability for HIVDR testing.

Evaluation of a novel in-house HIV-1 genotype drug resistance assay using clinical samples in China

2021 ◽  
Vol 19 ◽  
Author(s):  
Peijie Gao ◽  
Fengting Yu ◽  
Xiaozhen Yang ◽  
Dan Li ◽  
Yalun Shi ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Reverse Transcriptase ◽  
High Efficiency ◽  
Clinical Samples ◽  
Genotype Distribution ◽  
Resistance Mutations ◽  
Reverse Transcriptase Inhibitors ◽  
Nucleoside Reverse Transcriptase Inhibitors ◽  
Subtype B ◽  
Hiv 1

Background: HIV drug resistance poses a major challenge for anti-retroviral treatment (ART) and the prevention and control of HIV epidemic. Objective: The study aims to establish a novel in-house assay with high efficiency, named AP in-house method, that would be suitable for HIV-1 drug resistance detection in China. Methods: An in-house HIV-1 genotyping method was used to sequence the partial pol gene from 60 clinical plasma samples; the results of our test were compared with a commercial ViroSeq HIV-1 genotyping system. Results : Among sixty samples, 58(96.7%) were successfully amplified by AP in-house method, five of them harbored viral load below 1,000 copies/ml. The genotype distribution was 43.1% CRF07_BC (25/58), 39.7% CRF01_AE (23/58), 6.9% CRF55_01B (4/58), 5.2% subtype B (3/58) and 5.2% CRF08_BC (3/58). Compared with that of the ViroSeq system, the consistent rate of these nucleotides and amino acids obtained by AP in-house method was up to 99.5 ± 0.4% and 99.5 ± 0.4%, respectively. A total of 290 HIV-1 drug resistance mutations were identified by two methods, including 126 nucleoside reverse transcriptase inhibitors (NRTIs), 145 non-nucleoside reverse transcriptase inhibitors (NNRTIs) and 19 protease inhibitors (PIs) resistance mutations. Out of them, 94.1% (273/290) were completely concordant between the AP in-house method and the ViroSeq system. Conclusion: Overall, the evaluation of AP in-house method provided comparable results to those of the ViroSeq system on diversified HIV-1 subtypes in China.

scholarly journals Non-Nucleoside Reverse Transcriptase Inhibitors Join Forces with Integrase Inhibitors to Combat HIV

2020 ◽  
Vol 13 (6) ◽  
pp. 122
Author(s):  
Daniel M. Himmel ◽  
Eddy Arnold
Keyword(s):  
Reverse Transcriptase ◽  
Immune Deficiency Syndrome ◽  
Deficiency Syndrome ◽  
Strand Transfer ◽  
Hiv Integrase ◽  
Resistance Mutations ◽  
Reverse Transcriptase Inhibitors ◽  
Nucleoside Reverse Transcriptase Inhibitors ◽  
Novel Treatments ◽  
Wide Range

In the treatment of acquired immune deficiency syndrome (AIDS), the diarylpyrimidine (DAPY) analogs etravirine (ETR) and rilpivirine (RPV) have been widely effective against human immunodeficiency virus (HIV) variants that are resistant to other non-nucleoside reverse transcriptase inhibitors (NNRTIs). With non-inferior or improved efficacy, better safety profiles, and lower doses or pill burdens than other NNRTIs in the clinic, combination therapies including either of these two drugs have led to higher adherence than other NNRTI-containing treatments. In a separate development, HIV integrase strand transfer inhibitors (INSTIs) have shown efficacy in treating AIDS, including raltegravir (RAL), elvitegravir (EVG), cabotegravir (CAB), bictegravir (BIC), and dolutegravir (DTG). Of these, DTG and BIC perform better against a wide range of resistance mutations than other INSTIs. Nevertheless, drug-resistant combinations of mutations have begun to emerge against all DAPYs and INSTIs, attributable in part to non-adherence. New dual therapies that may promote better adherence combine ETR or RPV with an INSTI and have been safer and non-inferior to more traditional triple-drug treatments. Long-acting dual- and triple-therapies combining ETR or RPV with INSTIs are under study and may further improve adherence. Here, highly resistant emergent mutations and efficacy data on these novel treatments are reviewed. Overall, ETR or RPV, in combination with INSTIs, may be treatments of choice as long-term maintenance therapies that optimize efficacy, adherence, and safety.

scholarly journals INSTIs and NNRTIs Potently Inhibit HIV-1 Polypurine Tract Mutants in a Single Round Infection Assay

Viruses ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2501
Author(s):  
Steven J. Smith ◽  
Andrea Ferris ◽  
Xuezhi Zhao ◽  
Gary Pauly ◽  
Joel P. Schneider ◽  
...  
Keyword(s):  
Reverse Transcriptase ◽  
Envelope Gene ◽  
Strand Transfer ◽  
Resistance Mutations ◽  
Reverse Transcriptase Inhibitors ◽  
Nucleoside Reverse Transcriptase Inhibitors ◽  
Integrase Gene ◽  
Polypurine Tract ◽  
Emergence Of Resistance ◽  
Hiv 1

Integrase strand transfer inhibitors (INSTIs) are a class of antiretroviral compounds that prevent the insertion of a DNA copy of the viral genome into the host genome by targeting the viral enzyme integrase (IN). Dolutegravir (DTG) is a leading INSTI that is given, usually in combination with nucleoside reverse transcriptase inhibitors (NRTIs), to treat HIV-1 infections. The emergence of resistance to DTG and other leading INSTIs is rare. However, there are recent reports suggesting that drug resistance mutations can occur at positions outside the integrase gene either in the HIV-1 polypurine tract (PPT) or in the envelope gene (env). Here, we used single round infectivity assays to measure the antiviral potencies of several FDA-approved INSTIs and non-nucleoside reverse transcriptase inhibitors (NNRTIs) against a panel of HIV-1 PPT mutants. We also tested several of our promising INSTIs and NNRTIs in these assays. No measurable loss in potency was observed for either INSTIs or NNRTIs against the HIV-1 PPT mutants. This suggests that HIV-1 PPT mutants are not able, by themselves, to confer resistance to INSTIs or NNRTIs.

HIV-1 Resistance Profile of the Novel Nucleoside Reverse Transcriptase Inhibitor β-D-2′,3′-Dideoxy-2′,3′-Didehydro-5-Fluorocytidine (Reverset™)

2003 ◽  
Vol 14 (1) ◽  
pp. 49-59 ◽  
Author(s):  
Romas Geleziunas ◽  
Karen Gallagher ◽  
Hangchun Zhang ◽  
Lee Bacheler ◽  
Sena Garber ◽  
...  
Keyword(s):  
Reverse Transcriptase ◽  
Highly Active Antiretroviral Therapy ◽  
Resistance Mutations ◽  
Reverse Transcriptase Inhibitors ◽  
Nucleoside Reverse Transcriptase Inhibitors ◽  
Resistance Profile ◽  
Wide Range ◽  
Resistant Strains ◽  
Hiv 1

Nucleoside reverse transcriptase inhibitors (NRTIs) represent the cornerstone of highly active antiretroviral therapy when combined with non-nucleoside reverse transcriptase inhibitors (NNRTIs) or HIV-1 protease inhibitors (PIs). Unlike the NNRTIs and PIs, NRTIs must be successively phosphorylated by cellular kinases to a triphosphate form, which represents the active metabolite possessing antiviral activity. Emergence of viral resistance to NRTIs has severely hampered treatment options for persons infected with HIV-1. As such, there is an urgent need to develop NRTIs capable of suppressing NRTI-resistant strains of HIV-1. We have recently reported that the cytidine analogue D-d4FC (DPC817, Reverset™) effectively inhibits clinically prevalent resistant strains of HIV-1. In this report, we have extended these findings and now describe a detailed resistance profile for this novel NRTI. By examining a panel of 50 viruses carrying RTs derived from HIV-1 clinical isolates displaying a wide range of NRTI resistance mutations, we report that the median fold increase in effective antiviral concentration for such a panel of viruses is 3.2, which is comparable to tenofovir (2.8-fold) and didanosine (2.4-fold). D-d4FC is highly effective at inhibiting subsets of lamivudine-and zidovudine-resistant variants but, like other NRTIs, seems less potent against multi-NRTI-resistant viruses, particularly those carrying the Q151M complex of mutations. Finally, in vitro selections for HIV-1 mutants capable of replicating in the presence of D-d4FC yielded a mutant carrying the RT K65R mutation. This mutation confers 5.3- to 8.7-fold resistance to D-d4FC in vitro. These findings suggest that D-d4FC may represent an alternative NRTI for the treatment of individuals infected with lamivudine- and zidovudine-resistant strains of HIV-1.

scholarly journals ATP-Dependent Removal of Nucleoside Reverse Transcriptase Inhibitors by Human Immunodeficiency Virus Type 1 Reverse Transcriptase

2002 ◽  
Vol 46 (7) ◽  
pp. 2179-2184 ◽  
Author(s):  
Lisa K. Naeger ◽  
Nicolas A. Margot ◽  
Michael D. Miller
Keyword(s):  
Human Immunodeficiency Virus ◽  
Reverse Transcriptase ◽  
Resistance Mutations ◽  
Reverse Transcriptase Inhibitors ◽  
Nucleoside Reverse Transcriptase Inhibitors ◽  
Thymidine Analog ◽  
Immunodeficiency Virus ◽  
Analog Resistance ◽  
Deoxynucleoside Triphosphate

ABSTRACT Removal of nucleoside chain terminator inhibitors mediated by human immunodeficiency virus (HIV) reverse transcriptase (RT) using ATP as an acceptor molecule has been proposed as a novel mechanism of HIV resistance. Recombinant wild-type and mutant HIV type 1 (HIV-1) RT enzymes with thymidine analog resistance mutations D67N, K70R, and T215Y were analyzed for their ability to remove eight nucleoside reverse transcriptase inhibitors in the presence of physiological concentrations of ATP. The order for the rate of removal of the eight inhibitors by the mutant RT enzyme was zidovudine (AZT) > stavudine (d4T) ≫ zalcitabine (ddC) > abacavir > amdoxovir (DAPD) > lamivudine (3TC) > didanosine (ddI) > tenofovir. Thymidine analogs AZT and d4T were the most significantly removed by the mutant enzyme, suggesting that removal of these inhibitors by the ATP-dependent removal mechanism contributes to the AZT and d4T resistance observed in patients with HIV expressing thymidine analog resistance mutations. ATP-dependent removal of tenofovir was 22- to 35-fold less efficient than removal of d4T and AZT, respectively. The addition of ATP and the next complementary deoxynucleoside triphosphate caused a reduction of ATP-mediated removal of d4T, ddC, and DAPD, while AZT and abacavir removal was unaffected. The reduction of d4T, ddC, and DAPD removal in the presence of the deoxynucleoside triphosphate could explain the minor changes in susceptibility to these drugs observed in conventional in vitro phenotypic assays using cells that have higher deoxynucleoside triphosphate pools. The minimal removal of abacavir, ddC, DAPD, 3TC, ddI, and tenofovir is consistent with the minor changes in susceptibility to these drugs observed for HIV mutants with thymidine analog resistance mutations.

scholarly journals Transmitted drug resistance and transmission clusters among HIV-1 treatment-naïve patients in Guangdong, China: a cross-sectional study

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Yun Lan ◽  
Linghua Li ◽  
Xiang He ◽  
Fengyu Hu ◽  
Xizi Deng ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Reverse Transcriptase ◽  
Transmitted Drug Resistance ◽  
Resistance Mutations ◽  
Reverse Transcriptase Inhibitors ◽  
Nucleoside Reverse Transcriptase Inhibitors ◽  
Cross Sectional ◽  
Genetic Transmission ◽  
Treatment Naïve ◽  
Hiv 1

Abstract Background Transmitted drug resistance (TDR) that affects the effectiveness of the first-line antiretroviral therapy (ART) regimen is becoming prevalent worldwide. However, its prevalence and transmission among HIV-1 treatment-naïve patients in Guangdong, China are rarely reported. We aimed to comprehensively analyze the prevalence of TDR and the transmission clusters of HIV-1 infected persons before ART in Guangdong. Methods The HIV-1 treatment-naïve patients were recruited between January 2018 and December 2018. The HIV-1 pol region was amplified by reverse transcriptional PCR and sequenced by sanger sequencing. Genotypes, surveillance drug resistance mutations (SDRMs) and TDR were analyzed. Genetic transmission clusters among patients were identified by pairwise Tamura-Nei 93 genetic distance, with a threshold of 0.015. Results A total of 2368 (97.17%) HIV-1 pol sequences were successfully amplified and sequenced from the enrolled 2437 patients. CRF07_BC (35.90%, 850/2368), CRF01_AE (35.56%, 842/2368) and CRF55_01B (10.30%, 244/2368) were the main HIV-1 genotypes circulating in Guangdong. Twenty-one SDRMs were identified among fifty-two drug-resistant sequences. The overall prevalence of TDR was 2.20% (52/2368). Among the 2368 patients who underwent sequencing, 8 (0.34%) had TDR to protease inhibitors (PIs), 22 (0.93%) to nucleoside reverse transcriptase inhibitors (NRTIs), and 23 (0.97%) to non-nucleoside reverse transcriptase inhibitors (NNRTIs). Two (0.08%) sequences showed dual-class resistance to both NRTIs and NNRTIs, and no sequences showed triple-class resistance. A total of 1066 (45.02%) sequences were segregated into 194 clusters, ranging from 2 to 414 sequences. In total, 15 (28.85%) of patients with TDR were included in 9 clusters; one cluster contained two TDR sequences with the K103N mutation was observed. Conclusions There is high HIV-1 genetic heterogeneity among patients in Guangdong. Although the overall prevalence of TDR is low, it is still necessary to remain vigilant regarding some important SDRMs.

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