scholarly journals Signature Nucleotide Polymorphisms at Positions 64 and 65 in Reverse Transcriptase Favor the Selection of the K65R Resistance Mutation in HIV‐1 Subtype C

2009 ◽  
Vol 200 (8) ◽  
pp. 1202-1206 ◽  
Author(s):  
Cédric F. Invernizzi ◽  
Dimitrios Coutsinos ◽  
Maureen Oliveira ◽  
Daniela Moisi ◽  
Bluma G. Brenner ◽  
...  
Keyword(s):  
Reverse Transcriptase ◽  
Resistance Mutation ◽  
Nucleotide Polymorphisms ◽  
Subtype C ◽  
Hiv 1 ◽  
Selection Of

scholarly journals Analysis of drug resistance mutation and signature pattern in the archived DNA of HIV-1 infected North Indian patients

2020 ◽  
Author(s):  
Sushanta Kumar Barik ◽  
Keshar Kunja Mohanty ◽  
Partha Sarathi Mohanty ◽  
Luke Elizabeth Hanna ◽  
Ramesh Karunaianantham ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Reverse Transcriptase ◽  
Resistance Mutation ◽  
Drug Resistance Mutation ◽  
Reference Sequence ◽  
Protease Gene ◽  
Reverse Transcriptase Gene ◽  
Subtype C ◽  
Signature Pattern ◽  
Hiv 1

Abstract Background Characterization of drug resistance mutations and signature pattern in the archived DNA of HIV-1 infected North Indian patients.Methods Blood samples were collected from 9 patients enrolled in ART Centre, S.N. Medical College, Agra, North India from 1 year to = < 7 years. DNA was isolated and amplified for protease and reverse transcriptase genes using nested primers from WHO dried blood spot protocol 2010. The polymerase chain reaction products were sequenced and drug resistance mutation patterns were analysed using the HIV drug resistance database, Stanford University, USA. Various computational tools and websites like Stanford HIV drug resistance database, Viral epidemiological signature pattern analysis (VESPA), Hypermutation, SNAP version 2.1.1, Entropy were utilized for analysis of the sequence data.Results This study enables an analysis of archived DNA samples in patients having lower viral load and where the situation of HIV RNA isolation was negligible. Lamivudine associated drug-resistant mutations such as M184V/M184I, nevirapine associated mutations Y181C and H221Y and efavirenz associated mutations M230I were observed in two patients. No mutations were observed in the remaining seven patients. The signature pattern analysis of 9 protease and reverse transcriptase genes identified the conservation of amino acid sequences as compared to the reference sequence. The signature pattern of nucleotide substitution (synonymous to non-synonymous ratio) of the protease gene was 5.02 and the reverse transcriptase gene was 7.01. No hyper mutation was observed in the protease and reverse transcriptase gene of the archived DNA.Conclusions The analysis of the drug resistance mutation in the protease and reverse transcriptase gene of the archived DNA of HIV-1 subtype C infected patients over 1 to = < 7 years of first-line ART may be helpful in the treatment guideline in North Indian patients. A few signature amino acids were persisted in the reverse transcriptase and protease gene of similar HIV-1 subtype C infected patients over 1 to = < 7 years of first line ART in comparison to the reference sequence. This archived DNA drug resistance mutation testing could be an important tool when RNA testing becomes unsuccessful.

scholarly journals Incidence of the resistance mutation K65R on reverse transcriptase in different HIV-1 subtypes

2008 ◽  
Vol 11 (Suppl 1) ◽  
pp. P188
Author(s):  
D Turner ◽  
S Pollack ◽  
E Kachman ◽  
E Kedem ◽  
E Shahar ◽  
...  
Keyword(s):  
Reverse Transcriptase ◽  
Resistance Mutation ◽  
Hiv 1

scholarly journals Genetic diversity and primary resistance among HIV-1-positive patients from Maringá, Paraná, Brazil

2012 ◽  
Vol 54 (4) ◽  
pp. 207-213 ◽  
Author(s):  
Karine Vieira Gaspareto ◽  
Flávia Myrian Martins de Almeida Mello ◽  
José Ricardo Colleti Dias ◽  
Vera Alice Fernandes Meneguetti ◽  
Marta Evelyn Giansante Storti ◽  
...  
Keyword(s):  
Specific Antigen ◽  
Resistance Mutation ◽  
Drug Resistance Mutation ◽  
Subtype C ◽  
Primary Resistance ◽  
Subtype B ◽  
Pcr Products ◽  
Treatment Naïve ◽  
Positive Treatment ◽  
Hiv 1

The objective of this study is to identify subtypes of Human Immunodeficiency Virus type 1 (HIV-1) and to analyze the presence of mutations associated to antiretroviral resistance in the protease (PR) and reverse transcriptase (RT) regions from 48 HIV-1 positive treatment naïve patients from an outpatient clinic in Maringá, Paraná, Brazil. Sequencing was conducted using PR, partial RT and group-specific antigen gene (gag) nested PCR products from retrotranscribed RNA. Transmitted resistance was determined according to the Surveillance Drug Resistance Mutation List (SDRM) algorithm. Phylogenetic and SimPlot analysis of concatenated genetic segments classified sequences as subtype B 19/48 (39.6%), subtype C 12/48 (25%), subtype F 4/48 (8.3%), with 13/48 (27.1%) recombinant forms. Most recombinant forms were B mosaics (B/F 12.5%, B/C 10.4%), with one C/F (2.1%) and one complex B/C/F mosaic (2.1%). Low levels of transmitted resistance were found in this study, 2/48 (2.1% to NRTIs and 2.1% for PI). This preliminary data may subsidize the monitoring of the HIV evolution in the region.

scholarly journals L74V increases the reverse transcriptase content of HIV-1 virions with non-nucleoside reverse transcriptase drug-resistant mutations L100I+K103N and K101E+G190S, which results in increased fitness

2013 ◽  
Vol 94 (7) ◽  
pp. 1597-1607 ◽  
Author(s):  
Jiong Wang ◽  
Dongge Li ◽  
Robert A. Bambara ◽  
Hongmei Yang ◽  
Carrie Dykes
Keyword(s):  
Reverse Transcriptase ◽  
Resistance Mutation ◽  
Transcriptase Inhibitor ◽  
Rnase H ◽  
Drug Resistant ◽  
Resistance Mutations ◽  
Nnrti Resistance ◽  
Reverse Transcriptase Inhibitor ◽  
Subsequent Addition ◽  
Hiv 1

The fitness of non-nucleoside reverse transcriptase inhibitor (NNRTI) drug-resistant reverse transcriptase (RT) mutants of HIV-1 correlates with the amount of RT in the virions and the RNase H activity of the RT. We wanted to understand the mechanism by which secondary NNRTI-resistance mutations, L100I and K101E, and the nucleoside resistance mutation, L74V, alter the fitness of K103N and G190S viruses. We measured the amount of RT in virions and the polymerization and RNase H activities of mutant RTs compared to wild-type, K103N and G190S. We found that L100I, K101E and L74V did not change the polymerization or RNase H activities of K103N or G190S RTs. However, L100I and K101E reduced the amount of RT in the virions and subsequent addition of L74V restored RT levels back to those of G190S or K103N alone. We conclude that fitness changes caused by L100I, K101E and L74V derive from their effects on RT content.

scholarly journals Standardized Comparison of the Relative Impacts of HIV-1 Reverse Transcriptase (RT) Mutations on Nucleoside RT Inhibitor Susceptibility

2012 ◽  
Vol 56 (5) ◽  
pp. 2305-2313 ◽  
Author(s):  
George L. Melikian ◽  
Soo-Yon Rhee ◽  
Jonathan Taylor ◽  
W. Jeffrey Fessel ◽  
David Kaufman ◽  
...  
Keyword(s):  
Reverse Transcriptase ◽  
San Francisco ◽  
Resistance Mutation ◽  
Dynamic Susceptibility ◽  
Least Squares Regression ◽  
Resistance Mutations ◽  
Data Set ◽  
New Findings ◽  
The Impact ◽  
Hiv 1

ABSTRACTDetermining the phenotypic impacts of reverse transcriptase (RT) mutations on individual nucleoside RT inhibitors (NRTIs) has remained a statistical challenge because clinical NRTI-resistant HIV-1 isolates usually contain multiple mutations, often in complex patterns, complicating the task of determining the relative contribution of each mutation to HIV drug resistance. Furthermore, the NRTIs have highly variable dynamic susceptibility ranges, making it difficult to determine the relative effect of an RT mutation on susceptibility to different NRTIs. In this study, we analyzed 1,273 genotyped HIV-1 isolates for which phenotypic results were obtained using the PhenoSense assay (Monogram, South San Francisco, CA). We used a parsimonious feature selection algorithm, LASSO, to assess the possible contributions of 177 mutations that occurred in 10 or more isolates in our data set. We then used least-squares regression to quantify the impact of each LASSO-selected mutation on each NRTI. Our study provides a comprehensive view of the most common NRTI resistance mutations. Because our results were standardized, the study provides the first analysis that quantifies the relative phenotypic effects of NRTI resistance mutations on each of the NRTIs. In addition, the study contains new findings on the relative impacts of thymidine analog mutations (TAMs) on susceptibility to abacavir and tenofovir; the impacts of several known but incompletely characterized mutations, including E40F, V75T, Y115F, and K219R; and a tentative role in reduced NRTI susceptibility for K64H, a novel NRTI resistance mutation.

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