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.

Autor:	van Heerden JK; Wellcome Centre for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa., Meintjes G; Wellcome Centre for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa.; Department of Medicine, University of Cape Town and Groote Schuur Hospital, Cape Town, South Africa., Barr D; NHS Greater Glasgow and Clyde, Scotland, United Kingdom.; Institute of Infection and Global Health, University of Liverpool, Liverpool, United Kingdom., Zhao Y; Wellcome Centre for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa.; Department of Medicine, University of Cape Town and Groote Schuur Hospital, Cape Town, South Africa., Griesel R; Wellcome Centre for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa.; Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa., Keene CM; Médecins Sans Frontières, Cape Town, South Africa; and.; Health Systems Collaborative, NDM Centre for Global Health Research, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom., Wiesner L; Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa., Galileya LT; Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa., Denti P; Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa., Maartens G; Wellcome Centre for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa.; Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa.
Jazyk:	angličtina
Zdroj:	Journal of acquired immune deficiency syndromes (1999) [J Acquir Immune Defic Syndr] 2024 Mar 01; Vol. 95 (3), pp. 260-267.
DOI:	10.1097/QAI.0000000000003341
Abstrakt:	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. Competing Interests: The authors declare no conflict of interests. (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu