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HIV-1 integrase resistance associated mutations and the use of dolutegravir in Sub-Saharan Africa: A systematic review and meta-analysis
As sub-Saharan Africa (SSA) countries are transitioning to dolutegravir (DTG)-based ART, baseline data are required for optimal monitoring of therapeutic response. In this frame, we sought to generate up-to-date evidence on the use of integrase-strand transfer inhibitors (INSTI) and associated drug...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10021461/ https://www.ncbi.nlm.nih.gov/pubmed/36962573 http://dx.doi.org/10.1371/journal.pgph.0000826 |
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author | Ngoufack Jagni Semengue, Ezechiel Santoro, Maria Mercedes Ndze, Valantine Ngum Ka’e, Aude Christelle Yagai, Bouba Nka, Alex Durand Dambaya, Beatrice Takou, Desiré Teto, Georges Fabeni, Lavinia Colizzi, Vittorio Perno, Carlo-Federico Ceccherini-Silberstein, Francesca Fokam, Joseph |
author_facet | Ngoufack Jagni Semengue, Ezechiel Santoro, Maria Mercedes Ndze, Valantine Ngum Ka’e, Aude Christelle Yagai, Bouba Nka, Alex Durand Dambaya, Beatrice Takou, Desiré Teto, Georges Fabeni, Lavinia Colizzi, Vittorio Perno, Carlo-Federico Ceccherini-Silberstein, Francesca Fokam, Joseph |
author_sort | Ngoufack Jagni Semengue, Ezechiel |
collection | PubMed |
description | As sub-Saharan Africa (SSA) countries are transitioning to dolutegravir (DTG)-based ART, baseline data are required for optimal monitoring of therapeutic response. In this frame, we sought to generate up-to-date evidence on the use of integrase-strand transfer inhibitors (INSTI) and associated drug resistance mutations (DRMs) within SSA. In this systematic review and meta-analysis, we included randomized and non-randomized trials, cohort-studies, cross-sectional studies, and case-reports published on INSTI or integrase DRMs in SSA. We included studies of patients exposed to DTG, raltegravir (RAL) or elvitegravir (EVG). Primary outcomes were “the rate of virological control (VC:<50copies/ml)” and “the presence of DRMs” on INSTI-based regimens among patients in SSA. We synthesised extracted data using subgroup analysis, and random effect models were used where appropriate. Additional analyses were conducted to assess study heterogeneity. We identified 1,916 articles/citations through database searches, of which 26 were included in the analysis pertaining to 5,444 patients (mean age: 37±13 years), with 67.62% (3681/5444) female. Specifically, 46.15% (12/26) studies focused on DTG, 26.92% (7/26) on RAL, 23.08% (6/26) on both DTG and RAL, and 3.85% (1/26) on EVG. We found an increasing use of DTG overtime (0% before 2018 to 100% in 2021). Median treatment duration under INSTI-based regimens was 12 [9–36] months. Overall, the rate of VC was 88.51% [95%CI: 73.83–97.80] with DTG vs. 82.49% [95%CI: 55.76–99.45] and 96.55% [95%CI: 85.7–100.00] with RAL and EVG, respectively. In univariate analysis, VC with DTG-containing vs. other INSTI-regimens was significantly higher (OR = 1.44 [95%CI: 1.15–1.79], p = 0.0014). Among reported DRMs at failure, the only DTG resistance-mutations were G118R and R263K. In SSA, DTG presents a superiority effect in VC compared to other INSTIs. Nonetheless, the early detection of INSTI-DRMs calls for sentinel surveillance for a successful transition and a sustained efficacy of DTG in SSA. PROSPERO Registration Number: CRD42019122424. |
format | Online Article Text |
id | pubmed-10021461 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-100214612023-03-17 HIV-1 integrase resistance associated mutations and the use of dolutegravir in Sub-Saharan Africa: A systematic review and meta-analysis Ngoufack Jagni Semengue, Ezechiel Santoro, Maria Mercedes Ndze, Valantine Ngum Ka’e, Aude Christelle Yagai, Bouba Nka, Alex Durand Dambaya, Beatrice Takou, Desiré Teto, Georges Fabeni, Lavinia Colizzi, Vittorio Perno, Carlo-Federico Ceccherini-Silberstein, Francesca Fokam, Joseph PLOS Glob Public Health Research Article As sub-Saharan Africa (SSA) countries are transitioning to dolutegravir (DTG)-based ART, baseline data are required for optimal monitoring of therapeutic response. In this frame, we sought to generate up-to-date evidence on the use of integrase-strand transfer inhibitors (INSTI) and associated drug resistance mutations (DRMs) within SSA. In this systematic review and meta-analysis, we included randomized and non-randomized trials, cohort-studies, cross-sectional studies, and case-reports published on INSTI or integrase DRMs in SSA. We included studies of patients exposed to DTG, raltegravir (RAL) or elvitegravir (EVG). Primary outcomes were “the rate of virological control (VC:<50copies/ml)” and “the presence of DRMs” on INSTI-based regimens among patients in SSA. We synthesised extracted data using subgroup analysis, and random effect models were used where appropriate. Additional analyses were conducted to assess study heterogeneity. We identified 1,916 articles/citations through database searches, of which 26 were included in the analysis pertaining to 5,444 patients (mean age: 37±13 years), with 67.62% (3681/5444) female. Specifically, 46.15% (12/26) studies focused on DTG, 26.92% (7/26) on RAL, 23.08% (6/26) on both DTG and RAL, and 3.85% (1/26) on EVG. We found an increasing use of DTG overtime (0% before 2018 to 100% in 2021). Median treatment duration under INSTI-based regimens was 12 [9–36] months. Overall, the rate of VC was 88.51% [95%CI: 73.83–97.80] with DTG vs. 82.49% [95%CI: 55.76–99.45] and 96.55% [95%CI: 85.7–100.00] with RAL and EVG, respectively. In univariate analysis, VC with DTG-containing vs. other INSTI-regimens was significantly higher (OR = 1.44 [95%CI: 1.15–1.79], p = 0.0014). Among reported DRMs at failure, the only DTG resistance-mutations were G118R and R263K. In SSA, DTG presents a superiority effect in VC compared to other INSTIs. Nonetheless, the early detection of INSTI-DRMs calls for sentinel surveillance for a successful transition and a sustained efficacy of DTG in SSA. PROSPERO Registration Number: CRD42019122424. Public Library of Science 2022-10-11 /pmc/articles/PMC10021461/ /pubmed/36962573 http://dx.doi.org/10.1371/journal.pgph.0000826 Text en © 2022 Ngoufack Jagni Semengue et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Ngoufack Jagni Semengue, Ezechiel Santoro, Maria Mercedes Ndze, Valantine Ngum Ka’e, Aude Christelle Yagai, Bouba Nka, Alex Durand Dambaya, Beatrice Takou, Desiré Teto, Georges Fabeni, Lavinia Colizzi, Vittorio Perno, Carlo-Federico Ceccherini-Silberstein, Francesca Fokam, Joseph HIV-1 integrase resistance associated mutations and the use of dolutegravir in Sub-Saharan Africa: A systematic review and meta-analysis |
title | HIV-1 integrase resistance associated mutations and the use of dolutegravir in Sub-Saharan Africa: A systematic review and meta-analysis |
title_full | HIV-1 integrase resistance associated mutations and the use of dolutegravir in Sub-Saharan Africa: A systematic review and meta-analysis |
title_fullStr | HIV-1 integrase resistance associated mutations and the use of dolutegravir in Sub-Saharan Africa: A systematic review and meta-analysis |
title_full_unstemmed | HIV-1 integrase resistance associated mutations and the use of dolutegravir in Sub-Saharan Africa: A systematic review and meta-analysis |
title_short | HIV-1 integrase resistance associated mutations and the use of dolutegravir in Sub-Saharan Africa: A systematic review and meta-analysis |
title_sort | hiv-1 integrase resistance associated mutations and the use of dolutegravir in sub-saharan africa: a systematic review and meta-analysis |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10021461/ https://www.ncbi.nlm.nih.gov/pubmed/36962573 http://dx.doi.org/10.1371/journal.pgph.0000826 |
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