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Patterns of pretreatment drug resistance mutations of very early diagnosed and treated infants in Botswana
OBJECTIVE: To describe the occurrence of HIV drug resistance mutations (DRMs) in both intact and defective HIV-1 cell-associated DNA (HIV-1 CAD) among early-treated infants. DESIGN: The Botswana EIT Study (ClinicalTrials.gov NCT02369406) initiated antiretroviral therapy (ART) in the first week of li...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Lippincott Williams & Wilkins
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8631156/ https://www.ncbi.nlm.nih.gov/pubmed/34324451 http://dx.doi.org/10.1097/QAD.0000000000003041 |
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author | Moraka, Natasha Onalenna Garcia-Broncano, Pilar Hu, Zixin Ajibola, Gbolahan Bareng, Ontlametse T. Pretorius-Holme, Molly Maswabi, Kenneth Maphorisa, Comfort Mohammed, Terence Gaseitsiwe, Simani VanZyl, Gert U. Kuritzkes, Daniel R. Lichterfeld, Mathias Moyo, Sikhulile Shapiro, Roger L. |
author_facet | Moraka, Natasha Onalenna Garcia-Broncano, Pilar Hu, Zixin Ajibola, Gbolahan Bareng, Ontlametse T. Pretorius-Holme, Molly Maswabi, Kenneth Maphorisa, Comfort Mohammed, Terence Gaseitsiwe, Simani VanZyl, Gert U. Kuritzkes, Daniel R. Lichterfeld, Mathias Moyo, Sikhulile Shapiro, Roger L. |
author_sort | Moraka, Natasha Onalenna |
collection | PubMed |
description | OBJECTIVE: To describe the occurrence of HIV drug resistance mutations (DRMs) in both intact and defective HIV-1 cell-associated DNA (HIV-1 CAD) among early-treated infants. DESIGN: The Botswana EIT Study (ClinicalTrials.gov NCT02369406) initiated antiretroviral therapy (ART) in the first week of life and evaluated HIV-1 in plasma and peripheral blood mononuclear cells (PBMCs). METHODOLOGY: We analyzed 257 near-HIV-1 full-length sequences (nFLS) obtained by Illumina next-generation sequencing from infants near birth. Sanger sequencing of pol was performed for mothers at delivery and children with clinical failure through 96 weeks. DRMs were identified using the Stanford HIV Drug Resistance Database. RESULTS: In 27 infants, median PBMC HIV-1 proviral load was 492 copies/ml [IQR: 78–1246 copies/ml] at a median of 2 days (range 1–32); 18 (66.7%) had no DRMs detected; six (22.2%) had DRMs detected in defective DNA only, and three (11.1%) had DRMs in both defective and intact DNA (P = 0.09). A total of 60 of 151 (37.7%) defective sequences had at least one DRM: 31.8% NNRTI, 15.2% NRTI, 5.3% protease inhibitor, and 15.5% INSTI-associated mutations. In intact sequences, 33 of 106 (31.1%) had at least 1 DRM: 29.2% NNRTI, 7.5% NRTI, 0.9% protease inhibitor, and no INSTI-associated mutations. For all three infants with intact sequence DRMs, corresponding DRMs occurred in maternal plasma at delivery. Archived DRMs were detectable at a later clinical rebound on only one occasion. CONCLUSION: Defective HIV-1 cell-associated DNA sequences may overestimate the prevalence of drug resistance among early-treated children. The impact of DRMs from intact proviruses on long-term treatment outcomes warrants further investigation. |
format | Online Article Text |
id | pubmed-8631156 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Lippincott Williams & Wilkins |
record_format | MEDLINE/PubMed |
spelling | pubmed-86311562021-12-07 Patterns of pretreatment drug resistance mutations of very early diagnosed and treated infants in Botswana Moraka, Natasha Onalenna Garcia-Broncano, Pilar Hu, Zixin Ajibola, Gbolahan Bareng, Ontlametse T. Pretorius-Holme, Molly Maswabi, Kenneth Maphorisa, Comfort Mohammed, Terence Gaseitsiwe, Simani VanZyl, Gert U. Kuritzkes, Daniel R. Lichterfeld, Mathias Moyo, Sikhulile Shapiro, Roger L. AIDS Basic Science OBJECTIVE: To describe the occurrence of HIV drug resistance mutations (DRMs) in both intact and defective HIV-1 cell-associated DNA (HIV-1 CAD) among early-treated infants. DESIGN: The Botswana EIT Study (ClinicalTrials.gov NCT02369406) initiated antiretroviral therapy (ART) in the first week of life and evaluated HIV-1 in plasma and peripheral blood mononuclear cells (PBMCs). METHODOLOGY: We analyzed 257 near-HIV-1 full-length sequences (nFLS) obtained by Illumina next-generation sequencing from infants near birth. Sanger sequencing of pol was performed for mothers at delivery and children with clinical failure through 96 weeks. DRMs were identified using the Stanford HIV Drug Resistance Database. RESULTS: In 27 infants, median PBMC HIV-1 proviral load was 492 copies/ml [IQR: 78–1246 copies/ml] at a median of 2 days (range 1–32); 18 (66.7%) had no DRMs detected; six (22.2%) had DRMs detected in defective DNA only, and three (11.1%) had DRMs in both defective and intact DNA (P = 0.09). A total of 60 of 151 (37.7%) defective sequences had at least one DRM: 31.8% NNRTI, 15.2% NRTI, 5.3% protease inhibitor, and 15.5% INSTI-associated mutations. In intact sequences, 33 of 106 (31.1%) had at least 1 DRM: 29.2% NNRTI, 7.5% NRTI, 0.9% protease inhibitor, and no INSTI-associated mutations. For all three infants with intact sequence DRMs, corresponding DRMs occurred in maternal plasma at delivery. Archived DRMs were detectable at a later clinical rebound on only one occasion. CONCLUSION: Defective HIV-1 cell-associated DNA sequences may overestimate the prevalence of drug resistance among early-treated children. The impact of DRMs from intact proviruses on long-term treatment outcomes warrants further investigation. Lippincott Williams & Wilkins 2021-12-01 2021-09-14 /pmc/articles/PMC8631156/ /pubmed/34324451 http://dx.doi.org/10.1097/QAD.0000000000003041 Text en Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0 (https://creativecommons.org/licenses/by-nc-nd/4.0/) |
spellingShingle | Basic Science Moraka, Natasha Onalenna Garcia-Broncano, Pilar Hu, Zixin Ajibola, Gbolahan Bareng, Ontlametse T. Pretorius-Holme, Molly Maswabi, Kenneth Maphorisa, Comfort Mohammed, Terence Gaseitsiwe, Simani VanZyl, Gert U. Kuritzkes, Daniel R. Lichterfeld, Mathias Moyo, Sikhulile Shapiro, Roger L. Patterns of pretreatment drug resistance mutations of very early diagnosed and treated infants in Botswana |
title | Patterns of pretreatment drug resistance mutations of very early diagnosed and treated infants in Botswana |
title_full | Patterns of pretreatment drug resistance mutations of very early diagnosed and treated infants in Botswana |
title_fullStr | Patterns of pretreatment drug resistance mutations of very early diagnosed and treated infants in Botswana |
title_full_unstemmed | Patterns of pretreatment drug resistance mutations of very early diagnosed and treated infants in Botswana |
title_short | Patterns of pretreatment drug resistance mutations of very early diagnosed and treated infants in Botswana |
title_sort | patterns of pretreatment drug resistance mutations of very early diagnosed and treated infants in botswana |
topic | Basic Science |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8631156/ https://www.ncbi.nlm.nih.gov/pubmed/34324451 http://dx.doi.org/10.1097/QAD.0000000000003041 |
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