Unexpected interactions between dolutegravir and folate: randomised trial evidence from South Africa.
File(s)
Published version
Author(s)
Chandiwana, Nomathemba C
Chersich, Matthew
Venter, Willem Francois
Akpomiemie, Godspower
Hill, Andrew
Type
Journal Article
Abstract
OBJECTIVE: Dolutegravir exposure at conception was associated with a preliminary signal of increased infant neural tube defect (NTD) risk. As low maternal folate levels are linked with NTDs, 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, 1,053 treatment-naïve participants were randomised 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 count 356 cells/mm. 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. CONCLUSIONS: Unexpectedly, no declines were noted in the dolutegravir-containing arms, and concentrations were considerably higher than in the efavirenz arm. The possibility that dolutegravir may block cellular uptake of folate warrants investigation.
Date Issued
2021-02-02
Date Acceptance
2020-07-07
Citation
AIDS, 2021, 35 (2), pp.205-211
ISSN
0269-9370
Publisher
Lippincott, Williams & Wilkins
Start Page
205
End Page
211
Journal / Book Title
AIDS
Volume
35
Issue
2
Copyright Statement
© 2020 The Author(s). 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.
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.
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/33086234
Subjects
Virology
06 Biological Sciences
11 Medical and Health Sciences
17 Psychology and Cognitive Sciences
Publication Status
Published
Coverage Spatial
England
Date Publish Online
2021-02-02