Cargando…
Risk factors and outcomes for the Q151M and T69 insertion HIV-1 resistance mutations in historic UK data
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 re...
Autores principales: | , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2018
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5902836/ https://www.ncbi.nlm.nih.gov/pubmed/29661246 http://dx.doi.org/10.1186/s12981-018-0198-7 |
_version_ | 1783314822463488000 |
---|---|
author | Stirrup, Oliver T. Dunn, David T. Tostevin, Anna Sabin, Caroline A. Pozniak, Anton Asboe, David Cox, Alison Orkin, Chloe Martin, Fabiola Cane, Patricia |
author_facet | Stirrup, Oliver T. Dunn, David T. Tostevin, Anna Sabin, Caroline A. Pozniak, Anton Asboe, David Cox, Alison Orkin, Chloe Martin, Fabiola Cane, Patricia |
author_sort | Stirrup, Oliver T. |
collection | PubMed |
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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12981-018-0198-7) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-5902836 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-59028362018-04-23 Risk factors and outcomes for the Q151M and T69 insertion HIV-1 resistance mutations in historic UK data Stirrup, Oliver T. Dunn, David T. Tostevin, Anna Sabin, Caroline A. Pozniak, Anton Asboe, David Cox, Alison Orkin, Chloe Martin, Fabiola Cane, Patricia AIDS Res Ther Research 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12981-018-0198-7) contains supplementary material, which is available to authorized users. BioMed Central 2018-04-16 /pmc/articles/PMC5902836/ /pubmed/29661246 http://dx.doi.org/10.1186/s12981-018-0198-7 Text en © The Author(s) 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Stirrup, Oliver T. Dunn, David T. Tostevin, Anna Sabin, Caroline A. Pozniak, Anton Asboe, David Cox, Alison Orkin, Chloe Martin, Fabiola Cane, Patricia Risk factors and outcomes for the Q151M and T69 insertion HIV-1 resistance mutations in historic UK data |
title | Risk factors and outcomes for the Q151M and T69 insertion HIV-1 resistance mutations in historic UK data |
title_full | Risk factors and outcomes for the Q151M and T69 insertion HIV-1 resistance mutations in historic UK data |
title_fullStr | Risk factors and outcomes for the Q151M and T69 insertion HIV-1 resistance mutations in historic UK data |
title_full_unstemmed | Risk factors and outcomes for the Q151M and T69 insertion HIV-1 resistance mutations in historic UK data |
title_short | Risk factors and outcomes for the Q151M and T69 insertion HIV-1 resistance mutations in historic UK data |
title_sort | risk factors and outcomes for the q151m and t69 insertion hiv-1 resistance mutations in historic uk data |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5902836/ https://www.ncbi.nlm.nih.gov/pubmed/29661246 http://dx.doi.org/10.1186/s12981-018-0198-7 |
work_keys_str_mv | AT stirrupolivert riskfactorsandoutcomesfortheq151mandt69insertionhiv1resistancemutationsinhistoricukdata AT dunndavidt riskfactorsandoutcomesfortheq151mandt69insertionhiv1resistancemutationsinhistoricukdata AT tostevinanna riskfactorsandoutcomesfortheq151mandt69insertionhiv1resistancemutationsinhistoricukdata AT sabincarolinea riskfactorsandoutcomesfortheq151mandt69insertionhiv1resistancemutationsinhistoricukdata AT pozniakanton riskfactorsandoutcomesfortheq151mandt69insertionhiv1resistancemutationsinhistoricukdata AT asboedavid riskfactorsandoutcomesfortheq151mandt69insertionhiv1resistancemutationsinhistoricukdata AT coxalison riskfactorsandoutcomesfortheq151mandt69insertionhiv1resistancemutationsinhistoricukdata AT orkinchloe riskfactorsandoutcomesfortheq151mandt69insertionhiv1resistancemutationsinhistoricukdata AT martinfabiola riskfactorsandoutcomesfortheq151mandt69insertionhiv1resistancemutationsinhistoricukdata AT canepatricia riskfactorsandoutcomesfortheq151mandt69insertionhiv1resistancemutationsinhistoricukdata AT riskfactorsandoutcomesfortheq151mandt69insertionhiv1resistancemutationsinhistoricukdata AT riskfactorsandoutcomesfortheq151mandt69insertionhiv1resistancemutationsinhistoricukdata |