Characterization of drug resistance and the defective HIV reservoir in virally suppressed vertically infected children in Mali
© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissionsoup.com..
BACKGROUND: In the perspective of ART-free HIV remission, vertically infected children treated with suppressive ART from early infancy represent an optimal population model to better understand the genetic complexity of the reservoir.
OBJECTIVES: To evaluate the proportion of defective viral population and the genotypic resistance patterns in cell-associated HIV DNA.
METHODS: In a cohort including 93 ART-treated vertically HIV-infected (VHIV) children in Mali with plasma HIV-1 RNA ≤50 copies/mL for at least 6 months, we studied total HIV DNA, percentage of defective genomes and resistance by reverse transcriptase and protease bulk sequencing from whole blood in dried blood spots.
RESULTS: Children had a median age of 9.9 years at the time of inclusion (IQR = 7.6-13.4) and 3.3 years (IQR = 2-7) at ART initiation; median ART duration was 5.5 years (IQR = 3.7-7.3). The median level of total HIV DNA was 470 copies/106 cells with one patient presenting undetectable HIV DNA (<66 copies/106 cells). We observed the presence of at least one stop codon in viruses from 34 patients (37%). The presence of stop codons was not correlated with the level of HIV DNA or duration of ART. We showed a high prevalence of HIV-1 resistance in DNA with 26% of children harbouring virus resistant to at least one NRTI and 40% to at least one NNRTI.
CONCLUSIONS: While these VHIV children were successfully treated for a long time, they showed high prevalence of resistance in HIV DNA and a moderate defective HIV reservoir.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:75 |
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| Enthalten in: |
The Journal of antimicrobial chemotherapy - 75(2020), 5 vom: 01. Mai, Seite 1272-1279 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Brice, Josephine [VerfasserIn] |
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| Links: |
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| Themen: |
Anti-HIV Agents |
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| Anmerkungen: |
Date Completed 24.06.2021 Date Revised 24.06.2021 published: Print Citation Status MEDLINE |
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| doi: |
10.1093/jac/dkaa002 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM306675358 |
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| 245 | 1 | 0 | |a Characterization of drug resistance and the defective HIV reservoir in virally suppressed vertically infected children in Mali |
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| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissionsoup.com. | ||
| 520 | |a BACKGROUND: In the perspective of ART-free HIV remission, vertically infected children treated with suppressive ART from early infancy represent an optimal population model to better understand the genetic complexity of the reservoir | ||
| 520 | |a OBJECTIVES: To evaluate the proportion of defective viral population and the genotypic resistance patterns in cell-associated HIV DNA | ||
| 520 | |a METHODS: In a cohort including 93 ART-treated vertically HIV-infected (VHIV) children in Mali with plasma HIV-1 RNA ≤50 copies/mL for at least 6 months, we studied total HIV DNA, percentage of defective genomes and resistance by reverse transcriptase and protease bulk sequencing from whole blood in dried blood spots | ||
| 520 | |a RESULTS: Children had a median age of 9.9 years at the time of inclusion (IQR = 7.6-13.4) and 3.3 years (IQR = 2-7) at ART initiation; median ART duration was 5.5 years (IQR = 3.7-7.3). The median level of total HIV DNA was 470 copies/106 cells with one patient presenting undetectable HIV DNA (<66 copies/106 cells). We observed the presence of at least one stop codon in viruses from 34 patients (37%). The presence of stop codons was not correlated with the level of HIV DNA or duration of ART. We showed a high prevalence of HIV-1 resistance in DNA with 26% of children harbouring virus resistant to at least one NRTI and 40% to at least one NNRTI | ||
| 520 | |a CONCLUSIONS: While these VHIV children were successfully treated for a long time, they showed high prevalence of resistance in HIV DNA and a moderate defective HIV reservoir | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Anti-HIV Agents |2 NLM | |
| 700 | 1 | |a Sylla, Mariam |e verfasserin |4 aut | |
| 700 | 1 | |a Desire, Nathalie |e verfasserin |4 aut | |
| 700 | 1 | |a Sayon, Sophie |e verfasserin |4 aut | |
| 700 | 1 | |a Telly, Fatoumata |e verfasserin |4 aut | |
| 700 | 1 | |a Bocar-Fofana, Djeneba |e verfasserin |4 aut | |
| 700 | 1 | |a Murphy, Robert |e verfasserin |4 aut | |
| 700 | 1 | |a Peytavin, Gilles |e verfasserin |4 aut | |
| 700 | 1 | |a Diallo, Souleymane |e verfasserin |4 aut | |
| 700 | 1 | |a Nastouli, Eleni |e verfasserin |4 aut | |
| 700 | 1 | |a Calvez, Vincent |e verfasserin |4 aut | |
| 700 | 1 | |a Marcelin, Anne-Geneviève |e verfasserin |4 aut | |
| 700 | 1 | |a Maiga, Almoustapha Issiaka |e verfasserin |4 aut | |
| 700 | 1 | |a Lambert-Niclot, Sidonie |e verfasserin |4 aut | |
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