Risk factors and outcomes for the Q151M and T69 insertion HIV-1 resistance mutations in historic UK data View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2018-12

AUTHORS

Oliver T. Stirrup, David T. Dunn, Anna Tostevin, Caroline A. Sabin, Anton Pozniak, David Asboe, Alison Cox, Chloe Orkin, Fabiola Martin, Patricia Cane, the UK HIV Drug Resistance Database, the UK Collaborative HIV Cohort

ABSTRACT

BACKGROUND: The prevalence of HIV-1 resistance to antiretroviral therapies (ART) has declined in high-income countries over recent years, but drug resistance remains a substantial concern in many low and middle-income countries. The Q151M and T69 insertion (T69i) resistance mutations in the viral reverse transcriptase gene can reduce susceptibility to all nucleoside/tide analogue reverse transcriptase inhibitors, motivating the present study to investigate the risk factors and outcomes associated with these mutations. METHODS: We considered all data in the UK HIV Drug Resistance Database for blood samples obtained in the period 1997-2014. Where available, treatment history and patient outcomes were obtained through linkage to the UK Collaborative HIV Cohort study. A matched case-control approach was used to assess risk factors associated with the appearance of each of the mutations in ART-experienced patients, and survival analysis was used to investigate factors associated with viral suppression. A further analysis using matched controls was performed to investigate the impact of each mutation on survival. RESULTS: A total of 180 patients with Q151M mutation and 85 with T69i mutation were identified, almost entirely from before 2006. Occurrence of both the Q151M and T69i mutations was strongly associated with cumulative period of virological failure while on ART, and for Q151M there was a particular positive association with use of stavudine and negative association with use of boosted-protease inhibitors. Subsequent viral suppression was negatively associated with viral load at sequencing for both mutations, and for Q151M we found a negative association with didanosine use but a positive association with boosted-protease inhibitor use. The results obtained in these analyses were also consistent with potentially large associations with other drugs. Analyses were inconclusive regarding associations between the mutations and mortality, but mortality was high for patients with low CD4 at detection. CONCLUSIONS: The Q151M and T69i resistance mutations are now very rare in the UK. Our results suggest that good outcomes are possible for people with these mutations. However, in this historic sample, viral load and CD4 at detection were important factors in determining prognosis. More... »

PAGES

11

Identifiers

URI

http://scigraph.springernature.com/pub.10.1186/s12981-018-0198-7

DOI

http://dx.doi.org/10.1186/s12981-018-0198-7

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1103387727

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/29661246


Indexing Status Check whether this publication has been indexed by Scopus and Web Of Science using the SN Indexing Status Tool
Incoming Citations Browse incoming citations for this publication using opencitations.net

JSON-LD is the canonical representation for SciGraph data.

TIP: You can open this SciGraph record using an external JSON-LD service: JSON-LD Playground Google SDTT

[
  {
    "@context": "https://springernature.github.io/scigraph/jsonld/sgcontext.json", 
    "about": [
      {
        "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/1103", 
        "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
        "name": "Clinical Sciences", 
        "type": "DefinedTerm"
      }, 
      {
        "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/11", 
        "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
        "name": "Medical and Health Sciences", 
        "type": "DefinedTerm"
      }
    ], 
    "author": [
      {
        "affiliation": {
          "alternateName": "University College London", 
          "id": "https://www.grid.ac/institutes/grid.83440.3b", 
          "name": [
            "Centre for Clinical Research in Infection and Sexual Health, Institute for Global Health, University College London, London, UK"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Stirrup", 
        "givenName": "Oliver T.", 
        "id": "sg:person.0667525575.06", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0667525575.06"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "University College London", 
          "id": "https://www.grid.ac/institutes/grid.83440.3b", 
          "name": [
            "Centre for Clinical Research in Infection and Sexual Health, Institute for Global Health, University College London, London, UK"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Dunn", 
        "givenName": "David T.", 
        "id": "sg:person.010142470622.53", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.010142470622.53"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "University College London", 
          "id": "https://www.grid.ac/institutes/grid.83440.3b", 
          "name": [
            "Centre for Clinical Research in Infection and Sexual Health, Institute for Global Health, University College London, London, UK"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Tostevin", 
        "givenName": "Anna", 
        "id": "sg:person.010442363621.02", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.010442363621.02"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "University College London", 
          "id": "https://www.grid.ac/institutes/grid.83440.3b", 
          "name": [
            "Centre for Clinical Research, Epidemiology, Modelling and Evaluation, Institute for Global Health, University College London, Royal Free Campus, London, UK"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Sabin", 
        "givenName": "Caroline A.", 
        "id": "sg:person.015453740657.72", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.015453740657.72"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Chelsea and Westminster Hospital NHS Foundation Trust", 
          "id": "https://www.grid.ac/institutes/grid.428062.a", 
          "name": [
            "Chelsea and Westminster Hospital NHS Foundation Trust, London, UK"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Pozniak", 
        "givenName": "Anton", 
        "id": "sg:person.01204335567.62", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01204335567.62"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Chelsea and Westminster Hospital NHS Foundation Trust", 
          "id": "https://www.grid.ac/institutes/grid.428062.a", 
          "name": [
            "Chelsea and Westminster Hospital NHS Foundation Trust, London, UK"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Asboe", 
        "givenName": "David", 
        "id": "sg:person.01041212360.27", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01041212360.27"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Charing Cross Hospital", 
          "id": "https://www.grid.ac/institutes/grid.413820.c", 
          "name": [
            "Infection and Immunity laboratory, Charing Cross Hospital, London, UK"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Cox", 
        "givenName": "Alison", 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Barts Health NHS Trust", 
          "id": "https://www.grid.ac/institutes/grid.139534.9", 
          "name": [
            "Barts Health NHS Trust, London, UK"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Orkin", 
        "givenName": "Chloe", 
        "id": "sg:person.0605547265.03", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0605547265.03"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "University of Queensland", 
          "id": "https://www.grid.ac/institutes/grid.1003.2", 
          "name": [
            "Hull York Medical School, University of York, York, UK", 
            "Faculty of Medicine, University of Queensland, Brisbane, Australia"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Martin", 
        "givenName": "Fabiola", 
        "id": "sg:person.01367106177.37", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01367106177.37"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Department of Health", 
          "id": "https://www.grid.ac/institutes/grid.57981.32", 
          "name": [
            "High Containment Microbiology, Public Health England, Salisbury, UK"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Cane", 
        "givenName": "Patricia", 
        "id": "sg:person.01247677303.20", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01247677303.20"
        ], 
        "type": "Person"
      }, 
      {
        "familyName": "the UK HIV Drug Resistance Database", 
        "type": "Person"
      }, 
      {
        "familyName": "the UK Collaborative HIV Cohort", 
        "type": "Person"
      }
    ], 
    "citation": [
      {
        "id": "https://doi.org/10.1002/sim.1325", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1006015351"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/s0140-6736(12)61038-1", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1006992672"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1128/aac.45.6.1836-1842.2001", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1007992395"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1186/s13104-016-1884-y", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1009409439", 
          "https://doi.org/10.1186/s13104-016-1884-y"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1186/s13104-016-1884-y", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1009409439", 
          "https://doi.org/10.1186/s13104-016-1884-y"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1128/aac.44.8.2109-2117.2000", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1011038210"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1080/19345747.2011.618213", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1011488846"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1097/qai.0000000000000971", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1016554546"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1097/qai.0000000000000971", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1016554546"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1111/j.1468-1293.2004.00197.x", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1017272125"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1371/journal.pone.0073744", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1019744611"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1093/infdis/jit114", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1025977970"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1097/qad.0000000000001233", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1026692710"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1097/qad.0000000000001233", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1026692710"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1093/infdis/jit017", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1033922317"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1093/cid/ciw001", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1034489741"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/s2352-3018(14)00061-7", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1035219728"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/s1473-3099(09)70136-7", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1038357016"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1086/381097", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1040423338"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1093/cid/ciw128", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1040805755"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1097/qai.0b013e31823c8b69", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1048708104"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1097/qai.0b013e31823c8b69", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1048708104"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1093/infdis/jiq130", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1050223954"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1089/aid.2016.0133", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1059216411"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1093/jac/dkv500", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1059736151"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.18637/jss.v076.i01", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1068673140"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.3851/imp2437", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1071479663"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1097/qai.0000000000001285", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1074238076"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1097/qai.0000000000001285", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1074238076"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://app.dimensions.ai/details/publication/pub.1079005547", 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://app.dimensions.ai/details/publication/pub.1083844622", 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1093/infdis/jix089", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1083932420"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/s2352-3018(17)30065-6", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1085219499"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.cmi.2017.06.014", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1086137190"
        ], 
        "type": "CreativeWork"
      }
    ], 
    "datePublished": "2018-12", 
    "datePublishedReg": "2018-12-01", 
    "description": "BACKGROUND: The prevalence of HIV-1 resistance to antiretroviral therapies (ART) has declined in high-income countries over recent years, but drug resistance remains a substantial concern in many low and middle-income countries. The Q151M and T69 insertion (T69i) resistance mutations in the viral reverse transcriptase gene can reduce susceptibility to all nucleoside/tide analogue reverse transcriptase inhibitors, motivating the present study to investigate the risk factors and outcomes associated with these mutations.\nMETHODS: We considered all data in the UK HIV Drug Resistance Database for blood samples obtained in the period 1997-2014. Where available, treatment history and patient outcomes were obtained through linkage to the UK Collaborative HIV Cohort study. A matched case-control approach was used to assess risk factors associated with the appearance of each of the mutations in ART-experienced patients, and survival analysis was used to investigate factors associated with viral suppression. A further analysis using matched controls was performed to investigate the impact of each mutation on survival.\nRESULTS: A total of 180 patients with Q151M mutation and 85 with T69i mutation were identified, almost entirely from before 2006. Occurrence of both the Q151M and T69i mutations was strongly associated with cumulative period of virological failure while on ART, and for Q151M there was a particular positive association with use of stavudine and negative association with use of boosted-protease inhibitors. Subsequent viral suppression was negatively associated with viral load at sequencing for both mutations, and for Q151M we found a negative association with didanosine use but a positive association with boosted-protease inhibitor use. The results obtained in these analyses were also consistent with potentially large associations with other drugs. Analyses were inconclusive regarding associations between the mutations and mortality, but mortality was high for patients with low CD4 at detection.\nCONCLUSIONS: The Q151M and T69i resistance mutations are now very rare in the UK. Our results suggest that good outcomes are possible for people with these mutations. However, in this historic sample, viral load and CD4 at detection were important factors in determining prognosis.", 
    "genre": "research_article", 
    "id": "sg:pub.10.1186/s12981-018-0198-7", 
    "inLanguage": [
      "en"
    ], 
    "isAccessibleForFree": true, 
    "isFundedItemOf": [
      {
        "id": "sg:grant.2761341", 
        "type": "MonetaryGrant"
      }, 
      {
        "id": "sg:grant.4888308", 
        "type": "MonetaryGrant"
      }, 
      {
        "id": "sg:grant.3958461", 
        "type": "MonetaryGrant"
      }
    ], 
    "isPartOf": [
      {
        "id": "sg:journal.1034921", 
        "issn": [
          "1742-6405"
        ], 
        "name": "AIDS Research and Therapy", 
        "type": "Periodical"
      }, 
      {
        "issueNumber": "1", 
        "type": "PublicationIssue"
      }, 
      {
        "type": "PublicationVolume", 
        "volumeNumber": "15"
      }
    ], 
    "name": "Risk factors and outcomes for the Q151M and T69 insertion HIV-1 resistance mutations in historic UK data", 
    "pagination": "11", 
    "productId": [
      {
        "name": "readcube_id", 
        "type": "PropertyValue", 
        "value": [
          "918218703e724789176f690cc96324839b7b6c4fe01644b2fa1fb7404cde759d"
        ]
      }, 
      {
        "name": "pubmed_id", 
        "type": "PropertyValue", 
        "value": [
          "29661246"
        ]
      }, 
      {
        "name": "nlm_unique_id", 
        "type": "PropertyValue", 
        "value": [
          "101237921"
        ]
      }, 
      {
        "name": "doi", 
        "type": "PropertyValue", 
        "value": [
          "10.1186/s12981-018-0198-7"
        ]
      }, 
      {
        "name": "dimensions_id", 
        "type": "PropertyValue", 
        "value": [
          "pub.1103387727"
        ]
      }
    ], 
    "sameAs": [
      "https://doi.org/10.1186/s12981-018-0198-7", 
      "https://app.dimensions.ai/details/publication/pub.1103387727"
    ], 
    "sdDataset": "articles", 
    "sdDatePublished": "2019-04-11T13:18", 
    "sdLicense": "https://scigraph.springernature.com/explorer/license/", 
    "sdPublisher": {
      "name": "Springer Nature - SN SciGraph project", 
      "type": "Organization"
    }, 
    "sdSource": "s3://com-uberresearch-data-dimensions-target-20181106-alternative/cleanup/v134/2549eaecd7973599484d7c17b260dba0a4ecb94b/merge/v9/a6c9fde33151104705d4d7ff012ea9563521a3ce/jats-lookup/v90/0000000368_0000000368/records_78947_00000000.jsonl", 
    "type": "ScholarlyArticle", 
    "url": "https://link.springer.com/10.1186%2Fs12981-018-0198-7"
  }
]
 

Download the RDF metadata as:  json-ld nt turtle xml License info

HOW TO GET THIS DATA PROGRAMMATICALLY:

JSON-LD is a popular format for linked data which is fully compatible with JSON.

curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1186/s12981-018-0198-7'

N-Triples is a line-based linked data format ideal for batch operations.

curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1186/s12981-018-0198-7'

Turtle is a human-readable linked data format.

curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1186/s12981-018-0198-7'

RDF/XML is a standard XML format for linked data.

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1186/s12981-018-0198-7'


 

This table displays all metadata directly associated to this object as RDF triples.

247 TRIPLES      21 PREDICATES      58 URIs      21 LITERALS      9 BLANK NODES

Subject Predicate Object
1 sg:pub.10.1186/s12981-018-0198-7 schema:about anzsrc-for:11
2 anzsrc-for:1103
3 schema:author N53cb052fb8734fc09df26a6b7d56b52f
4 schema:citation sg:pub.10.1186/s13104-016-1884-y
5 https://app.dimensions.ai/details/publication/pub.1079005547
6 https://app.dimensions.ai/details/publication/pub.1083844622
7 https://doi.org/10.1002/sim.1325
8 https://doi.org/10.1016/j.cmi.2017.06.014
9 https://doi.org/10.1016/s0140-6736(12)61038-1
10 https://doi.org/10.1016/s1473-3099(09)70136-7
11 https://doi.org/10.1016/s2352-3018(14)00061-7
12 https://doi.org/10.1016/s2352-3018(17)30065-6
13 https://doi.org/10.1080/19345747.2011.618213
14 https://doi.org/10.1086/381097
15 https://doi.org/10.1089/aid.2016.0133
16 https://doi.org/10.1093/cid/ciw001
17 https://doi.org/10.1093/cid/ciw128
18 https://doi.org/10.1093/infdis/jiq130
19 https://doi.org/10.1093/infdis/jit017
20 https://doi.org/10.1093/infdis/jit114
21 https://doi.org/10.1093/infdis/jix089
22 https://doi.org/10.1093/jac/dkv500
23 https://doi.org/10.1097/qad.0000000000001233
24 https://doi.org/10.1097/qai.0000000000000971
25 https://doi.org/10.1097/qai.0000000000001285
26 https://doi.org/10.1097/qai.0b013e31823c8b69
27 https://doi.org/10.1111/j.1468-1293.2004.00197.x
28 https://doi.org/10.1128/aac.44.8.2109-2117.2000
29 https://doi.org/10.1128/aac.45.6.1836-1842.2001
30 https://doi.org/10.1371/journal.pone.0073744
31 https://doi.org/10.18637/jss.v076.i01
32 https://doi.org/10.3851/imp2437
33 schema:datePublished 2018-12
34 schema:datePublishedReg 2018-12-01
35 schema:description BACKGROUND: The prevalence of HIV-1 resistance to antiretroviral therapies (ART) has declined in high-income countries over recent years, but drug resistance remains a substantial concern in many low and middle-income countries. The Q151M and T69 insertion (T69i) resistance mutations in the viral reverse transcriptase gene can reduce susceptibility to all nucleoside/tide analogue reverse transcriptase inhibitors, motivating the present study to investigate the risk factors and outcomes associated with these mutations. METHODS: We considered all data in the UK HIV Drug Resistance Database for blood samples obtained in the period 1997-2014. Where available, treatment history and patient outcomes were obtained through linkage to the UK Collaborative HIV Cohort study. A matched case-control approach was used to assess risk factors associated with the appearance of each of the mutations in ART-experienced patients, and survival analysis was used to investigate factors associated with viral suppression. A further analysis using matched controls was performed to investigate the impact of each mutation on survival. RESULTS: A total of 180 patients with Q151M mutation and 85 with T69i mutation were identified, almost entirely from before 2006. Occurrence of both the Q151M and T69i mutations was strongly associated with cumulative period of virological failure while on ART, and for Q151M there was a particular positive association with use of stavudine and negative association with use of boosted-protease inhibitors. Subsequent viral suppression was negatively associated with viral load at sequencing for both mutations, and for Q151M we found a negative association with didanosine use but a positive association with boosted-protease inhibitor use. The results obtained in these analyses were also consistent with potentially large associations with other drugs. Analyses were inconclusive regarding associations between the mutations and mortality, but mortality was high for patients with low CD4 at detection. CONCLUSIONS: The Q151M and T69i resistance mutations are now very rare in the UK. Our results suggest that good outcomes are possible for people with these mutations. However, in this historic sample, viral load and CD4 at detection were important factors in determining prognosis.
36 schema:genre research_article
37 schema:inLanguage en
38 schema:isAccessibleForFree true
39 schema:isPartOf N4870d83f2b4e4a3bacb5e1704043fa8f
40 Nedeea46d6a594ac1a199a3bb733ea526
41 sg:journal.1034921
42 schema:name Risk factors and outcomes for the Q151M and T69 insertion HIV-1 resistance mutations in historic UK data
43 schema:pagination 11
44 schema:productId N3bae8c37c54946779e4d4a95394e9cb9
45 N59c9c9496a4641b48401bf81c7d206d0
46 N9e2e4bafcc7845e6803a44bb19d20d93
47 Nb87657a8f470447d8dc9973f9047b455
48 Nceff8c5e68e64b50b430cccefea4c109
49 schema:sameAs https://app.dimensions.ai/details/publication/pub.1103387727
50 https://doi.org/10.1186/s12981-018-0198-7
51 schema:sdDatePublished 2019-04-11T13:18
52 schema:sdLicense https://scigraph.springernature.com/explorer/license/
53 schema:sdPublisher Nf9d5837fcbe24a8d97c8558914dd4b2d
54 schema:url https://link.springer.com/10.1186%2Fs12981-018-0198-7
55 sgo:license sg:explorer/license/
56 sgo:sdDataset articles
57 rdf:type schema:ScholarlyArticle
58 N13e9f633ea4747f4bd8c795f62cfbac9 rdf:first Nceabefa57eeb4109b5ab9919e845766d
59 rdf:rest rdf:nil
60 N16604b7456dd44079d6bfcde593ab32f rdf:first sg:person.01367106177.37
61 rdf:rest N4590daf2546741bf8497bfb898429ae1
62 N189c8c905ab1442a8787c93e23299ae0 rdf:first sg:person.010442363621.02
63 rdf:rest N6bd4dab787bd4f1bb5b2dff2463a299a
64 N1a10922d4e0a4d318acc90f16846e595 rdf:first N514b9bdc22e2421bb8268233228d2ba1
65 rdf:rest N13e9f633ea4747f4bd8c795f62cfbac9
66 N2b9c0727c48b43d69fb2e7206d6721fd rdf:first sg:person.01204335567.62
67 rdf:rest N79b152f9a946449db627c328ad5caa5d
68 N3b6bc76c8e20410e82b0901140db3a23 rdf:first Nd0d0162b3edb4cbb9a22074b74ec7f4a
69 rdf:rest Nc5486f1ded924bc3b81aa83217fcf62b
70 N3bae8c37c54946779e4d4a95394e9cb9 schema:name readcube_id
71 schema:value 918218703e724789176f690cc96324839b7b6c4fe01644b2fa1fb7404cde759d
72 rdf:type schema:PropertyValue
73 N4590daf2546741bf8497bfb898429ae1 rdf:first sg:person.01247677303.20
74 rdf:rest N1a10922d4e0a4d318acc90f16846e595
75 N4870d83f2b4e4a3bacb5e1704043fa8f schema:issueNumber 1
76 rdf:type schema:PublicationIssue
77 N514b9bdc22e2421bb8268233228d2ba1 schema:familyName the UK HIV Drug Resistance Database
78 rdf:type schema:Person
79 N53cb052fb8734fc09df26a6b7d56b52f rdf:first sg:person.0667525575.06
80 rdf:rest Nb535028621ad4f31917a96c333b598a2
81 N59c9c9496a4641b48401bf81c7d206d0 schema:name doi
82 schema:value 10.1186/s12981-018-0198-7
83 rdf:type schema:PropertyValue
84 N6bd4dab787bd4f1bb5b2dff2463a299a rdf:first sg:person.015453740657.72
85 rdf:rest N2b9c0727c48b43d69fb2e7206d6721fd
86 N79b152f9a946449db627c328ad5caa5d rdf:first sg:person.01041212360.27
87 rdf:rest N3b6bc76c8e20410e82b0901140db3a23
88 N9e2e4bafcc7845e6803a44bb19d20d93 schema:name nlm_unique_id
89 schema:value 101237921
90 rdf:type schema:PropertyValue
91 Nb535028621ad4f31917a96c333b598a2 rdf:first sg:person.010142470622.53
92 rdf:rest N189c8c905ab1442a8787c93e23299ae0
93 Nb87657a8f470447d8dc9973f9047b455 schema:name pubmed_id
94 schema:value 29661246
95 rdf:type schema:PropertyValue
96 Nc5486f1ded924bc3b81aa83217fcf62b rdf:first sg:person.0605547265.03
97 rdf:rest N16604b7456dd44079d6bfcde593ab32f
98 Nceabefa57eeb4109b5ab9919e845766d schema:familyName the UK Collaborative HIV Cohort
99 rdf:type schema:Person
100 Nceff8c5e68e64b50b430cccefea4c109 schema:name dimensions_id
101 schema:value pub.1103387727
102 rdf:type schema:PropertyValue
103 Nd0d0162b3edb4cbb9a22074b74ec7f4a schema:affiliation https://www.grid.ac/institutes/grid.413820.c
104 schema:familyName Cox
105 schema:givenName Alison
106 rdf:type schema:Person
107 Nedeea46d6a594ac1a199a3bb733ea526 schema:volumeNumber 15
108 rdf:type schema:PublicationVolume
109 Nf9d5837fcbe24a8d97c8558914dd4b2d schema:name Springer Nature - SN SciGraph project
110 rdf:type schema:Organization
111 anzsrc-for:11 schema:inDefinedTermSet anzsrc-for:
112 schema:name Medical and Health Sciences
113 rdf:type schema:DefinedTerm
114 anzsrc-for:1103 schema:inDefinedTermSet anzsrc-for:
115 schema:name Clinical Sciences
116 rdf:type schema:DefinedTerm
117 sg:grant.2761341 http://pending.schema.org/fundedItem sg:pub.10.1186/s12981-018-0198-7
118 rdf:type schema:MonetaryGrant
119 sg:grant.3958461 http://pending.schema.org/fundedItem sg:pub.10.1186/s12981-018-0198-7
120 rdf:type schema:MonetaryGrant
121 sg:grant.4888308 http://pending.schema.org/fundedItem sg:pub.10.1186/s12981-018-0198-7
122 rdf:type schema:MonetaryGrant
123 sg:journal.1034921 schema:issn 1742-6405
124 schema:name AIDS Research and Therapy
125 rdf:type schema:Periodical
126 sg:person.010142470622.53 schema:affiliation https://www.grid.ac/institutes/grid.83440.3b
127 schema:familyName Dunn
128 schema:givenName David T.
129 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.010142470622.53
130 rdf:type schema:Person
131 sg:person.01041212360.27 schema:affiliation https://www.grid.ac/institutes/grid.428062.a
132 schema:familyName Asboe
133 schema:givenName David
134 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01041212360.27
135 rdf:type schema:Person
136 sg:person.010442363621.02 schema:affiliation https://www.grid.ac/institutes/grid.83440.3b
137 schema:familyName Tostevin
138 schema:givenName Anna
139 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.010442363621.02
140 rdf:type schema:Person
141 sg:person.01204335567.62 schema:affiliation https://www.grid.ac/institutes/grid.428062.a
142 schema:familyName Pozniak
143 schema:givenName Anton
144 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01204335567.62
145 rdf:type schema:Person
146 sg:person.01247677303.20 schema:affiliation https://www.grid.ac/institutes/grid.57981.32
147 schema:familyName Cane
148 schema:givenName Patricia
149 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01247677303.20
150 rdf:type schema:Person
151 sg:person.01367106177.37 schema:affiliation https://www.grid.ac/institutes/grid.1003.2
152 schema:familyName Martin
153 schema:givenName Fabiola
154 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01367106177.37
155 rdf:type schema:Person
156 sg:person.015453740657.72 schema:affiliation https://www.grid.ac/institutes/grid.83440.3b
157 schema:familyName Sabin
158 schema:givenName Caroline A.
159 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.015453740657.72
160 rdf:type schema:Person
161 sg:person.0605547265.03 schema:affiliation https://www.grid.ac/institutes/grid.139534.9
162 schema:familyName Orkin
163 schema:givenName Chloe
164 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0605547265.03
165 rdf:type schema:Person
166 sg:person.0667525575.06 schema:affiliation https://www.grid.ac/institutes/grid.83440.3b
167 schema:familyName Stirrup
168 schema:givenName Oliver T.
169 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0667525575.06
170 rdf:type schema:Person
171 sg:pub.10.1186/s13104-016-1884-y schema:sameAs https://app.dimensions.ai/details/publication/pub.1009409439
172 https://doi.org/10.1186/s13104-016-1884-y
173 rdf:type schema:CreativeWork
174 https://app.dimensions.ai/details/publication/pub.1079005547 schema:CreativeWork
175 https://app.dimensions.ai/details/publication/pub.1083844622 schema:CreativeWork
176 https://doi.org/10.1002/sim.1325 schema:sameAs https://app.dimensions.ai/details/publication/pub.1006015351
177 rdf:type schema:CreativeWork
178 https://doi.org/10.1016/j.cmi.2017.06.014 schema:sameAs https://app.dimensions.ai/details/publication/pub.1086137190
179 rdf:type schema:CreativeWork
180 https://doi.org/10.1016/s0140-6736(12)61038-1 schema:sameAs https://app.dimensions.ai/details/publication/pub.1006992672
181 rdf:type schema:CreativeWork
182 https://doi.org/10.1016/s1473-3099(09)70136-7 schema:sameAs https://app.dimensions.ai/details/publication/pub.1038357016
183 rdf:type schema:CreativeWork
184 https://doi.org/10.1016/s2352-3018(14)00061-7 schema:sameAs https://app.dimensions.ai/details/publication/pub.1035219728
185 rdf:type schema:CreativeWork
186 https://doi.org/10.1016/s2352-3018(17)30065-6 schema:sameAs https://app.dimensions.ai/details/publication/pub.1085219499
187 rdf:type schema:CreativeWork
188 https://doi.org/10.1080/19345747.2011.618213 schema:sameAs https://app.dimensions.ai/details/publication/pub.1011488846
189 rdf:type schema:CreativeWork
190 https://doi.org/10.1086/381097 schema:sameAs https://app.dimensions.ai/details/publication/pub.1040423338
191 rdf:type schema:CreativeWork
192 https://doi.org/10.1089/aid.2016.0133 schema:sameAs https://app.dimensions.ai/details/publication/pub.1059216411
193 rdf:type schema:CreativeWork
194 https://doi.org/10.1093/cid/ciw001 schema:sameAs https://app.dimensions.ai/details/publication/pub.1034489741
195 rdf:type schema:CreativeWork
196 https://doi.org/10.1093/cid/ciw128 schema:sameAs https://app.dimensions.ai/details/publication/pub.1040805755
197 rdf:type schema:CreativeWork
198 https://doi.org/10.1093/infdis/jiq130 schema:sameAs https://app.dimensions.ai/details/publication/pub.1050223954
199 rdf:type schema:CreativeWork
200 https://doi.org/10.1093/infdis/jit017 schema:sameAs https://app.dimensions.ai/details/publication/pub.1033922317
201 rdf:type schema:CreativeWork
202 https://doi.org/10.1093/infdis/jit114 schema:sameAs https://app.dimensions.ai/details/publication/pub.1025977970
203 rdf:type schema:CreativeWork
204 https://doi.org/10.1093/infdis/jix089 schema:sameAs https://app.dimensions.ai/details/publication/pub.1083932420
205 rdf:type schema:CreativeWork
206 https://doi.org/10.1093/jac/dkv500 schema:sameAs https://app.dimensions.ai/details/publication/pub.1059736151
207 rdf:type schema:CreativeWork
208 https://doi.org/10.1097/qad.0000000000001233 schema:sameAs https://app.dimensions.ai/details/publication/pub.1026692710
209 rdf:type schema:CreativeWork
210 https://doi.org/10.1097/qai.0000000000000971 schema:sameAs https://app.dimensions.ai/details/publication/pub.1016554546
211 rdf:type schema:CreativeWork
212 https://doi.org/10.1097/qai.0000000000001285 schema:sameAs https://app.dimensions.ai/details/publication/pub.1074238076
213 rdf:type schema:CreativeWork
214 https://doi.org/10.1097/qai.0b013e31823c8b69 schema:sameAs https://app.dimensions.ai/details/publication/pub.1048708104
215 rdf:type schema:CreativeWork
216 https://doi.org/10.1111/j.1468-1293.2004.00197.x schema:sameAs https://app.dimensions.ai/details/publication/pub.1017272125
217 rdf:type schema:CreativeWork
218 https://doi.org/10.1128/aac.44.8.2109-2117.2000 schema:sameAs https://app.dimensions.ai/details/publication/pub.1011038210
219 rdf:type schema:CreativeWork
220 https://doi.org/10.1128/aac.45.6.1836-1842.2001 schema:sameAs https://app.dimensions.ai/details/publication/pub.1007992395
221 rdf:type schema:CreativeWork
222 https://doi.org/10.1371/journal.pone.0073744 schema:sameAs https://app.dimensions.ai/details/publication/pub.1019744611
223 rdf:type schema:CreativeWork
224 https://doi.org/10.18637/jss.v076.i01 schema:sameAs https://app.dimensions.ai/details/publication/pub.1068673140
225 rdf:type schema:CreativeWork
226 https://doi.org/10.3851/imp2437 schema:sameAs https://app.dimensions.ai/details/publication/pub.1071479663
227 rdf:type schema:CreativeWork
228 https://www.grid.ac/institutes/grid.1003.2 schema:alternateName University of Queensland
229 schema:name Faculty of Medicine, University of Queensland, Brisbane, Australia
230 Hull York Medical School, University of York, York, UK
231 rdf:type schema:Organization
232 https://www.grid.ac/institutes/grid.139534.9 schema:alternateName Barts Health NHS Trust
233 schema:name Barts Health NHS Trust, London, UK
234 rdf:type schema:Organization
235 https://www.grid.ac/institutes/grid.413820.c schema:alternateName Charing Cross Hospital
236 schema:name Infection and Immunity laboratory, Charing Cross Hospital, London, UK
237 rdf:type schema:Organization
238 https://www.grid.ac/institutes/grid.428062.a schema:alternateName Chelsea and Westminster Hospital NHS Foundation Trust
239 schema:name Chelsea and Westminster Hospital NHS Foundation Trust, London, UK
240 rdf:type schema:Organization
241 https://www.grid.ac/institutes/grid.57981.32 schema:alternateName Department of Health
242 schema:name High Containment Microbiology, Public Health England, Salisbury, UK
243 rdf:type schema:Organization
244 https://www.grid.ac/institutes/grid.83440.3b schema:alternateName University College London
245 schema:name Centre for Clinical Research in Infection and Sexual Health, Institute for Global Health, University College London, London, UK
246 Centre for Clinical Research, Epidemiology, Modelling and Evaluation, Institute for Global Health, University College London, Royal Free Campus, London, UK
247 rdf:type schema:Organization
 




Preview window. Press ESC to close (or click here)


...