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 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 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 Drug Resistance Mutation L76V Alters Nonpolar Interactions at the Flap–Core Interface of HIV-1 Protease

ACS Omega ◽  
2018 ◽  
Vol 3 (9) ◽  
pp. 12132-12140 ◽  
Author(s):  
Andres Wong-Sam ◽  
Yuan-Fang Wang ◽  
Ying Zhang ◽  
Arun K. Ghosh ◽  
Robert W. Harrison ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Resistance Mutation ◽  
Drug Resistance Mutation ◽  
Hiv 1

scholarly journals Monitoring of HIV Drug Resistance Mutations in Newly Diagnosed Patients in Cyprus (2010–2012)

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S424-S424
Author(s):  
Ioannis Demetriades
Keyword(s):  
Drug Resistance ◽  
Phylogenetic Trees ◽  
Resistance Mutation ◽  
Drug Resistance Mutation ◽  
High Rate ◽  
Resistance Testing ◽  
Newly Diagnosed ◽  
Resistance Mutations ◽  
Subtype B ◽  
Hiv 1

Abstract Background A molecular epidemiology study of HIV-1 infection was conducted in 100 HIV-1 diagnosed and untreated patients in Cyprus representing 65.4 percent of all the reported HIV-1 infections in Cyprus between 2010 and 2012. Methods Eighty-two patients were newly diagnosed (genotypic drug resistance testing within six months from diagnosis), and 18 patients were HIV-1 diagnosed for a longer period or the diagnosis date was unknown. Results Phylogenetic trees of the pol sequences obtained in this study with reference sequences indicated that subtypes B and A1 were the most common subtypes present and accounted for 41.0 and 19.0% respectively, followed by subtype C (7.0%), F1 (8.0%), CRF02_AG (4.0%), A2 (2.0%), other CRFs (7.0%) and unknown recombinant forms, URFs (12%). Most of newly-diagnosed study subjects were Cypriots (63%), males (78%) with median age 39 (Interquartile Range, IQR 33–48) reporting having sex with other men, MSM (51%). Conclusion A high rate of clustered transmission of subtype B drug-sensitive strains to reverse transcriptase and protease inhibitors was observed among MSM. Twenty-eight out of forty-one MSM study subjects (68.0%) infected were implicated in five transmission clusters, two of which are subtype A1 and three subtype B strains. The two largest MSM subtype B clusters included nine and eight Cypriot men, respectively, living in all major cities in Cyprus. There were only three newly diagnosed patients with transmitted drug resistant HIV-1 strains, one study subject from the United Kingdom infected with subtype B strain and one from Romania with subtype A2 strain, both with the PI drug resistance mutation M46L and one patient from Greece with subtype A1 strain with the NNRTI drug resistance mutation K103N. Disclosures All authors: No reported disclosures.

scholarly journals Nucleic Acid Template and the Risk of a PCR-Induced HIV-1 Drug Resistance Mutation

PLoS ONE ◽  
2010 ◽  
Vol 5 (6) ◽  
pp. e10992 ◽  
Author(s):  
Vici Varghese ◽  
Elijah Wang ◽  
Farbod Babrzadeh ◽  
Michael H. Bachmann ◽  
Rajin Shahriar ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Nucleic Acid ◽  
Resistance Mutation ◽  
Drug Resistance Mutation ◽  
Hiv 1

Emergence of drug resistance-associated mutations in HIV-1 subtype C protease gene in north India

Virus Genes ◽  
2013 ◽  
Vol 47 (3) ◽  
pp. 422-428 ◽  
Author(s):  
Mohd Azam ◽  
Abida Malik ◽  
Meher Rizvi ◽  
Supriya Singh ◽  
Poonam Gupta ◽  
...  
Keyword(s):  
Drug Resistance ◽  
North India ◽  
Protease Gene ◽  
Subtype C ◽  
Hiv 1

scholarly journals Differential Persistence of Transmitted HIV-1 Drug Resistance Mutation Classes

2011 ◽  
Vol 203 (8) ◽  
pp. 1174-1181 ◽  
Author(s):  
Vivek Jain ◽  
Maria C. Sucupira ◽  
Peter Bacchetti ◽  
Wendy Hartogensis ◽  
Ricardo S. Diaz ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Resistance Mutation ◽  
Drug Resistance Mutation ◽  
Hiv 1

scholarly journals Deep Sequencing of HIV-1 RNA and DNA in Newly Diagnosed Patients with Baseline Drug Resistance Showed No Indications for Hidden Resistance and Is Biased by Strong Interference of Hypermutation

2016 ◽  
Vol 54 (6) ◽  
pp. 1605-1615 ◽  
Author(s):  
Kenny Dauwe ◽  
Delfien Staelens ◽  
Leen Vancoillie ◽  
Virginie Mortier ◽  
Chris Verhofstede
Keyword(s):  
Drug Resistance ◽  
Reverse Transcriptase ◽  
Deep Sequencing ◽  
Resistance Mutation ◽  
Wild Type Virus ◽  
Multiple Resistance ◽  
Newly Diagnosed ◽  
Resistance Mutations ◽  
Hiv 1 ◽  
Rna And Dna

Deep sequencing of plasma RNA or proviral DNA may be an interesting alternative to population sequencing for the detection of baseline transmitted HIV-1 drug resistance. Using a Roche 454 GS Junior HIV-1 prototype kit, we performed deep sequencing of the HIV-1 protease and reverse transcriptase genes on paired plasma and buffy coat samples from newly diagnosed HIV-1-positive individuals. Selection was based on the outcome of population sequencing and included 12 patients with either a revertant amino acid at codon 215 of the reverse transcriptase or a singleton resistance mutation, 4 patients with multiple resistance mutations, and 4 patients with wild-type virus. Deep sequencing of RNA and DNA detected 6 and 43 mutations, respectively, that were not identified by population sequencing. A subsequently performed hypermutation analysis, however, revealed hypermutation in 61.19% of 3,188 DNA reads with a resistance mutation. The removal of hypermutated reads dropped the number of additional mutations in DNA from 43 to 17. No hypermutation evidence was found in the RNA reads. Five of the 6 additional RNA mutations and all additional DNA mutations, after full exclusion of hypermutation bias, were observed in the 3 individuals with multiple resistance mutations detected by population sequencing. Despite focused selection of patients with T215 revertants or singleton mutations, deep sequencing failed to identify the resistant T215Y/F or M184V or any other resistance mutation, indicating that in most of these cases there is no hidden resistance and that the virus detected at diagnosis by population sequencing is the original infecting variant.

scholarly journals The L76V Drug Resistance Mutation Decreases the Dimer Stability and Rate of Autoprocessing of HIV-1 Protease by Reducing Internal Hydrophobic Contacts

Biochemistry ◽  
2011 ◽  
Vol 50 (21) ◽  
pp. 4786-4795 ◽  
Author(s):  
John M. Louis ◽  
Ying Zhang ◽  
Jane M. Sayer ◽  
Yuan-Fang Wang ◽  
Robert W. Harrison ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Resistance Mutation ◽  
Drug Resistance Mutation ◽  
Hiv 1
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