ArticleAIDS (London, England)2011
Switching between raltegravir resistance pathways analyzed by deep sequencing.
Article in AIDS (London, England), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 31 citations in OpenAlex.
- Comparison of illumina and 454 deep sequencing in participants failing raltegravir-based antiretroviral therapy.PloS one · 2014Trial
- A general and biomedical perspective of viral quasispecies.RNA (New York, N.Y.) · 2025Review
- Full-Length Envelope Analyzer (FLEA): A tool for longitudinal analysis of viral amplicons.PLoS computational biology · 2018Article
- Impact of the HIV-1 genetic background and HIV-1 population size on the evolution of raltegravir resistance.Retrovirology · 2018Article
- The Role of HIV-1 Drug-Resistant Minority Variants in Treatment Failure.The Journal of infectious diseases · 2017Review
- Drug Susceptibility and Viral Fitness of HIV-1 with Integrase Strand Transfer Inhibitor Resistance Substitution Q148R or N155H in Combination with Nucleoside/Nucleotide Reverse Transcriptase Inhibitor Resistance Substitutions.Antimicrobial agents and chemotherapy · 2016Article
- Adaptation on a genomic scale.eLife · 2015Article
- Targeted deep sequencing of HIV-1 using the IonTorrentPGM platform.Journal of virological methods · 2014Article
- High-Throughput Sequencing, a VersatileWeapon to Support Genome-Based Diagnosis in Infectious Diseases: Applications to Clinical Bacteriology.Pathogens (Basel, Switzerland) · 2014Review
- Next-Generation Sequencing to Help Monitor Patients Infected with HIV: Ready for Clinical Use?Current infectious disease reports · 2014Article
- Sensitive deep-sequencing-based HIV-1 genotyping assay to simultaneously determine susceptibility to protease, reverse transcriptase, integrase, and maturation inhibitors, as well as HIV-1 coreceptor tropism.Antimicrobial agents and chemotherapy · 2014Article
- Multiple genetic pathways involving amino acid position 143 of HIV-1 integrase are preferentially associated with specific secondary amino acid substitutions and confer resistance to raltegravir and cross-resistance to elvitegravir.Antimicrobial agents and chemotherapy · 2013Article
- Impact of primary elvitegravir resistance-associated mutations in HIV-1 integrase on drug susceptibility and viral replication fitness.Antimicrobial agents and chemotherapy · 2013Article
- Clinical implications of HIV-1 minority variants.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2013Article
- Plasmodium falciparum-like parasites infecting wild apes in southern Cameroon do not represent a recurrent source of human malaria.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- Substitutions at amino acid positions 143, 148, and 155 of HIV-1 integrase define distinct genetic barriers to raltegravir resistance in vivo.Journal of virology · 2012Article
- Viral quasispecies evolution.Microbiology and molecular biology reviews : MMBR · 2012Review
- Article
- Use of four next-generation sequencing platforms to determine HIV-1 coreceptor tropism.PloS one · 2012Article
- Challenges and opportunities in estimating viral genetic diversity from next-generation sequencing data.Frontiers in microbiology · 2012Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
objectiveOur objective was to analyze the pathways leading to resistance of HIV to the integrase (IN) inhibitor raltegravir (RAL).
designThree HIV-infected individuals exhibiting RAL resistance pathway switching were characterized using longitudinal analysis of viral samples from plasma.
methods454/Roche pyrosequencing was used to generate approximately 74,000 sequence reads from the integrase coding region. Effects of error were controlled by denoising with Pyronoise, and by comparison to approximately 142,000 control reads from HIV(NL4-3). Viral lineages were modeled quantitatively using viral serial pathway analysis (vSPA).
resultsAll three patients showed transitions from the N155H pathway to the Q148H/G140S pathway. Analysis with vSPA revealed complex pathways to the final genotype, probably involving both de-novo mutation and recombination. No reads contained both the N155H and Q148H drug resistance mutations (DRMs), indicating that the double mutant is not a prominent intermediate, consistent with low fitness. To characterize possible drug-resistant variants circulating prior to therapy, we sequenced approximately 70,000 reads from samples collected prior to initiating treatment. Although some preexisting drug-resistant variants were detected, N155H, the first major DRM present after initiating RAL therapy, was not detected.
conclusionThe main DRMs are present at very low levels if at all prior to initiating therapy. We also outline general methods for deep sequence analysis of DRMs in longitudinal HIV samples.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.