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
Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved..
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 (<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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:95 |
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| Enthalten in: |
Journal of acquired immune deficiency syndromes (1999) - 95(2024), 3 vom: 01. März, Seite 260-267 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
van Heerden, Jennifer Kate [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 28.02.2024 Date Revised 07.04.2024 published: Print Citation Status MEDLINE |
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| doi: |
10.1097/QAI.0000000000003341 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM368981754 |
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| 100 | 1 | |a van Heerden, Jennifer Kate |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a 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 |
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| 500 | |a Date Completed 28.02.2024 | ||
| 500 | |a Date Revised 07.04.2024 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved. | ||
| 520 | |a 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 | ||
| 520 | |a SETTING: Three primary care clinics in Khayelitsha, Cape Town, South Africa | ||
| 520 | |a 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 (<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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 7 | |a Tenofovir |2 NLM | |
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| 650 | 7 | |a Piperazines |2 NLM | |
| 650 | 7 | |a Pyridones |2 NLM | |
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| 700 | 1 | |a Barr, David |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Ying |e verfasserin |4 aut | |
| 700 | 1 | |a Griesel, Rulan |e verfasserin |4 aut | |
| 700 | 1 | |a Keene, Claire Marriott |e verfasserin |4 aut | |
| 700 | 1 | |a Wiesner, Lubbe |e verfasserin |4 aut | |
| 700 | 1 | |a Galileya, Lufina Tsirizani |e verfasserin |4 aut | |
| 700 | 1 | |a Denti, Paolo |e verfasserin |4 aut | |
| 700 | 1 | |a Maartens, Gary |e verfasserin |4 aut | |
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