Relationship between tenofovir diphosphate concentrations in dried blood spots and virological outcomes after initiating tenofovir–lamivudine–dolutegravir as first-line or second-line antiretroviral therapy. van Heerden, J. K., Meintjes, G. A, Barr, D., Zhao, Y., Griesel, R., Keene, C. M., Wiesner, L., Galileya, L. T., Denti, P., & Maartens, G. Journal of Acquired Immune Deficiency Syndromes, 95(3):260–267, mar, 2024. ![Relationship between tenofovir diphosphate concentrations in dried blood spots and virological outcomes after initiating tenofovir–lamivudine–dolutegravir as first-line or second-line antiretroviral therapy [link]](https://bibbase.org/img/filetypes/link.svg "link")
Paper doi abstract bibtex Background: Tenofovir diphosphate (TFV-DP) concentration in dried blood spots is a marker of long-term adherence. We investigated the relationship between TFV-DP concentrations and virological outcomes in participants initiating tenofovir–lamivudine–dolutegravir (TLD) as first-line or second-line antiretroviral therapy. Setting: Three primary care clinics in Khayelitsha, Cape Town, South Africa. Methods: We conducted a post hoc analysis of 2 randomized controlled trials of participants initiating TLD. TFV-DP concentrations and viral loads were measured at 12, 24, and 48 weeks. Multivariable logistic regression was performed to assess the association with virological suppression (\textless50 copies/mL) per natural logarithm increase in TFV-DP concentration. Generalized estimating equations with logit link were used to assess associations with virological rebound. The Akaike Information Criterion and Quasi-likelihood Information Criteria were used to compare models built on continuous TFV-DP data to 4 previously defined concentration categories. Results: We included 294 participants in the analysis, 188 (64%) of whom initiated TLD as second-line therapy. Adjusted odds ratios (95% CIs) of virological suppression were 2.12 (1.23, 3.75), 3.11 (1.84, 5.65), and 4.69 (2.81, 8.68) per natural logarithm increase in TFV-DP concentration at weeks 12, 24, and 48, respectively. In participants with virological suppression at week 12, the adjusted odds ratio for remaining virologically suppressed was 3.63 (95% CI: 2.21 to 5.69) per natural logarithm increase in TFV-DP concentration. Models using continuous TFV-DP data had lower Akaike Information Criterion and Quasi-likelihood Information Criteria values than those using categorical data for predicting virological outcomes. Conclusion: TFV-DP concentrations in dried blood spots exhibit a dose–response relationship with viral load. Analyzing TFV-DP concentrations as continuous variables rather than conventional categorization may be appropriate.
@article{VanHeerden2024a,
abstract = {Background: Tenofovir diphosphate (TFV-DP) concentration in dried blood spots is a marker of long-term adherence. We investigated the relationship between TFV-DP concentrations and virological outcomes in participants initiating tenofovir–lamivudine–dolutegravir (TLD) as first-line or second-line antiretroviral therapy. Setting: Three primary care clinics in Khayelitsha, Cape Town, South Africa. Methods: We conducted a post hoc analysis of 2 randomized controlled trials of participants initiating TLD. TFV-DP concentrations and viral loads were measured at 12, 24, and 48 weeks. Multivariable logistic regression was performed to assess the association with virological suppression ({\textless}50 copies/mL) per natural logarithm increase in TFV-DP concentration. Generalized estimating equations with logit link were used to assess associations with virological rebound. The Akaike Information Criterion and Quasi-likelihood Information Criteria were used to compare models built on continuous TFV-DP data to 4 previously defined concentration categories. Results: We included 294 participants in the analysis, 188 (64{\%}) of whom initiated TLD as second-line therapy. Adjusted odds ratios (95{\%} CIs) of virological suppression were 2.12 (1.23, 3.75), 3.11 (1.84, 5.65), and 4.69 (2.81, 8.68) per natural logarithm increase in TFV-DP concentration at weeks 12, 24, and 48, respectively. In participants with virological suppression at week 12, the adjusted odds ratio for remaining virologically suppressed was 3.63 (95{\%} CI: 2.21 to 5.69) per natural logarithm increase in TFV-DP concentration. Models using continuous TFV-DP data had lower Akaike Information Criterion and Quasi-likelihood Information Criteria values than those using categorical data for predicting virological outcomes. Conclusion: TFV-DP concentrations in dried blood spots exhibit a dose–response relationship with viral load. Analyzing TFV-DP concentrations as continuous variables rather than conventional categorization may be appropriate.},
author = {van Heerden, Jennifer Kate and Meintjes, Graeme A and Barr, David and Zhao, Ying and Griesel, Rulan and Keene, Claire Marriott and Wiesner, Lubbe and Galileya, Lufina Tsirizani and Denti, Paolo and Maartens, Gary},
doi = {10.1097/QAI.0000000000003341},
file = {:C$\backslash$:/Users/01462563/OneDrive - University of Cape Town/Documents/CIDRI-Africa papers and outputs/van Heerden et al - 2024- relationship{\_}between{\_}tenofovir{\_}diphosphate.7.pdf:pdf},
issn = {1525-4135},
journal = {Journal of Acquired Immune Deficiency Syndromes},
keywords = {fund{\_}ack,original},
mendeley-tags = {fund{\_}ack,original},
month = {mar},
number = {3},
pages = {260--267},
pmid = {38408216},
title = {{Relationship between tenofovir diphosphate concentrations in dried blood spots and virological outcomes after initiating tenofovir–lamivudine–dolutegravir as first-line or second-line antiretroviral therapy}},
url = {https://journals.lww.com/jaids/fulltext/2024/03010/relationship{\_}between{\_}tenofovir{\_}diphosphate.7.aspx},
volume = {95},
year = {2024}
}
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Methods: We conducted a post hoc analysis of 2 randomized controlled trials of participants initiating TLD. TFV-DP concentrations and viral loads were measured at 12, 24, and 48 weeks. Multivariable logistic regression was performed to assess the association with virological suppression (\\textless50 copies/mL) per natural logarithm increase in TFV-DP concentration. Generalized estimating equations with logit link were used to assess associations with virological rebound. The Akaike Information Criterion and Quasi-likelihood Information Criteria were used to compare models built on continuous TFV-DP data to 4 previously defined concentration categories. Results: We included 294 participants in the analysis, 188 (64%) of whom initiated TLD as second-line therapy. Adjusted odds ratios (95% CIs) of virological suppression were 2.12 (1.23, 3.75), 3.11 (1.84, 5.65), and 4.69 (2.81, 8.68) per natural logarithm increase in TFV-DP concentration at weeks 12, 24, and 48, respectively. In participants with virological suppression at week 12, the adjusted odds ratio for remaining virologically suppressed was 3.63 (95% CI: 2.21 to 5.69) per natural logarithm increase in TFV-DP concentration. Models using continuous TFV-DP data had lower Akaike Information Criterion and Quasi-likelihood Information Criteria values than those using categorical data for predicting virological outcomes. Conclusion: TFV-DP concentrations in dried blood spots exhibit a dose–response relationship with viral load. 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