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Unexpected interactions between dolutegravir and folate: randomized trial evidence from South Africa
Dolutegravir exposure at conception was associated with a preliminary signal of increased infant neural tube defect risk. As low maternal folate levels are linked with neural tube defects, we aimed to assess serum folate concentrations in women starting dolutegravir. DESIGN: We analysed serum folate...
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/PMC7810415/ https://www.ncbi.nlm.nih.gov/pubmed/33086234 http://dx.doi.org/10.1097/QAD.0000000000002741 |
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author | Chandiwana, Nomathemba C. Chersich, Matthew Venter, W.D. François Akpomiemie, Godspower Hill, Andrew Simmons, Bryony Lockman, Shahin Serenata, Celicia M. Fairlie, Lee Moorhouse, Michelle A. |
author_facet | Chandiwana, Nomathemba C. Chersich, Matthew Venter, W.D. François Akpomiemie, Godspower Hill, Andrew Simmons, Bryony Lockman, Shahin Serenata, Celicia M. Fairlie, Lee Moorhouse, Michelle A. |
author_sort | Chandiwana, Nomathemba C. |
collection | PubMed |
description | Dolutegravir exposure at conception was associated with a preliminary signal of increased infant neural tube defect risk. As low maternal folate levels are linked with neural tube defects, we aimed to assess serum folate concentrations in women starting dolutegravir. DESIGN: We analysed serum folate concentrations from stored plasma among women enrolled in the South African ADVANCE trial. METHODS: We compared changes in mean serum folate and occurrence of low serum folate (<14.0 nmol/l) at weeks 0, 12 and 24 across study arms. In ADVANCE, 1053 treatment-naïve participants were randomized to initiate tenofovir–alafenamide/emtricitabine + dolutegravir (TAF/FTC + DTG), tenofovir–disoproxil–fumarate (TDF)/FTC + DTG or TDF/FTC/efavirenz (EFV). RESULTS: Analysis includes 406 females, mean age 31.5 years and baseline CD4(+) cell count 356 cells/μl. At baseline, folate concentrations were similar across treatment arms. However, serum folate increased over 12 weeks in the TAF/FTC + DTG arm (+4.0 ± 8.1 nmol/l), while folate concentrations decreased slightly in the TDF/FTC + DTG arm (−1.8 ± 8.9 nmol/l) and decreased in the TDF/FTC/EFV arm (−5.9 ± 8.1 nmol/l). Women taking TDF/FTC/EFV had low folate concentrations at both 12 and 24 weeks compared with the other arms (P < 0.001). Of 26 women who became pregnant on study before week 24, folate concentrations increased between baseline and 12 weeks by a mean 2.4 ± 7.1 nmol/l in the TAF/FTC + DTG arm and 2.3 ± 8.4 nmol/l in the TDF/FTC + DTG arm, but decreased by −3.3 ± 8.1 with TDF/FTC/EFV arm. CONCLUSION: Unexpectedly, no declines were noted in the dolutegravir-containing arms, and concentrations were considerably higher than in the EFV arm. The possibility that dolutegravir may block cellular uptake of folate warrants investigation. |
format | Online Article Text |
id | pubmed-7810415 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Lippincott Williams & Wilkins |
record_format | MEDLINE/PubMed |
spelling | pubmed-78104152021-02-01 Unexpected interactions between dolutegravir and folate: randomized trial evidence from South Africa Chandiwana, Nomathemba C. Chersich, Matthew Venter, W.D. François Akpomiemie, Godspower Hill, Andrew Simmons, Bryony Lockman, Shahin Serenata, Celicia M. Fairlie, Lee Moorhouse, Michelle A. AIDS Basic Science Dolutegravir exposure at conception was associated with a preliminary signal of increased infant neural tube defect risk. As low maternal folate levels are linked with neural tube defects, we aimed to assess serum folate concentrations in women starting dolutegravir. DESIGN: We analysed serum folate concentrations from stored plasma among women enrolled in the South African ADVANCE trial. METHODS: We compared changes in mean serum folate and occurrence of low serum folate (<14.0 nmol/l) at weeks 0, 12 and 24 across study arms. In ADVANCE, 1053 treatment-naïve participants were randomized to initiate tenofovir–alafenamide/emtricitabine + dolutegravir (TAF/FTC + DTG), tenofovir–disoproxil–fumarate (TDF)/FTC + DTG or TDF/FTC/efavirenz (EFV). RESULTS: Analysis includes 406 females, mean age 31.5 years and baseline CD4(+) cell count 356 cells/μl. At baseline, folate concentrations were similar across treatment arms. However, serum folate increased over 12 weeks in the TAF/FTC + DTG arm (+4.0 ± 8.1 nmol/l), while folate concentrations decreased slightly in the TDF/FTC + DTG arm (−1.8 ± 8.9 nmol/l) and decreased in the TDF/FTC/EFV arm (−5.9 ± 8.1 nmol/l). Women taking TDF/FTC/EFV had low folate concentrations at both 12 and 24 weeks compared with the other arms (P < 0.001). Of 26 women who became pregnant on study before week 24, folate concentrations increased between baseline and 12 weeks by a mean 2.4 ± 7.1 nmol/l in the TAF/FTC + DTG arm and 2.3 ± 8.4 nmol/l in the TDF/FTC + DTG arm, but decreased by −3.3 ± 8.1 with TDF/FTC/EFV arm. CONCLUSION: Unexpectedly, no declines were noted in the dolutegravir-containing arms, and concentrations were considerably higher than in the EFV arm. The possibility that dolutegravir may block cellular uptake of folate warrants investigation. Lippincott Williams & Wilkins 2021-02-02 2021-10-20 /pmc/articles/PMC7810415/ /pubmed/33086234 http://dx.doi.org/10.1097/QAD.0000000000002741 Text en Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. http://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 |
spellingShingle | Basic Science Chandiwana, Nomathemba C. Chersich, Matthew Venter, W.D. François Akpomiemie, Godspower Hill, Andrew Simmons, Bryony Lockman, Shahin Serenata, Celicia M. Fairlie, Lee Moorhouse, Michelle A. Unexpected interactions between dolutegravir and folate: randomized trial evidence from South Africa |
title | Unexpected interactions between dolutegravir and folate: randomized trial evidence from South Africa |
title_full | Unexpected interactions between dolutegravir and folate: randomized trial evidence from South Africa |
title_fullStr | Unexpected interactions between dolutegravir and folate: randomized trial evidence from South Africa |
title_full_unstemmed | Unexpected interactions between dolutegravir and folate: randomized trial evidence from South Africa |
title_short | Unexpected interactions between dolutegravir and folate: randomized trial evidence from South Africa |
title_sort | unexpected interactions between dolutegravir and folate: randomized trial evidence from south africa |
topic | Basic Science |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7810415/ https://www.ncbi.nlm.nih.gov/pubmed/33086234 http://dx.doi.org/10.1097/QAD.0000000000002741 |
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