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Engagement in Mental Health Care is Associated with Higher Cumulative Drug Exposure and Adherence to Antiretroviral Therapy

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Abstract

Mental health (MH) disorders are more prevalent among persons living with HIV compared to the general population, and may contribute to suboptimal adherence to antiretroviral therapy (ART). Tenofovir-diphosphate (TFV-DP), the phosphorylated anabolite of tenofovir (TFV), is a biomarker with a 17-day half-life in red blood cells. TFV-DP can be measured in dried blood spots (DBS) using liquid chromatography/tandem mass spectrometry (LC-MS/MS) to assess adherence and cumulative drug exposure to tenofovir disoproxil fumarate (TDF)-based ART. From a larger clinical cohort (N = 807), TFV-DP concentrations and a paired HIV viral load were available from 521 participants at their enrollment visit. We used multivariable linear regression to evaluate the association between TFV-DP in DBS and engagement in MH care. After adjusting for clinical covariates, participants with MH disorders who were engaged in MH care had 40% higher TFV-DP compared to participants with MH disorders who were not engaged in MH care (p < 0.001), and similar TFV-DP to participants without MH disorders (p = 0.219). Further research is needed to identify the mechanism(s) for these findings, with the goal of optimizing engagement and retention in MH care strategies to improve ART adherence and clinical outcomes in PLWH with MH disorders.

Resumen

Las enfermedades mentales (EMs) son más frecuentes en personas que viven con VIH (PVIH), y pueden reducir la adherencia a la terapia antirretroviral (TARV). El difosfato de tenofovir (DF-TFV), el anabolito activo del tenofovir (TFV), tiene una vida media de 17 días en los eritrocitos y es cuantificable en gotas de sangre desecada (GSD) mediante cromatografía liquida y espectrometría de masa. El DF-TFV sirve come medida de adherencia y exposición acumulativa a la TARV basada en el fumarato de tenofovir disoproxil (TDF). En este estudio analizamos las concentraciones de DF-TFV en 521 PVIH derivadas de una cohorte clínica de 807 PVIH tratadas con TDF, con el objetivo de identificar si existe alguna asociación entre el DF-TFV y el cuidado activo de una EM en pacientes con este diagnóstico. Usando regresión lineal múltiple ajustada, en este análisis encontramos una reducción del 40% en las concentraciones de DF-TFV en las PVIH recibiendo tratamiento de una EM en comparación con las PVIH con un diagnóstico de EM sin recibir tratamiento activo (p<0.001), pero concentraciones similares a las de PVIH sin diagnóstico de EM (p=0.219). Las causas de estas diferencias deben ser investigadas en estudios adicionales con el fin de optimizar el tratamiento activo de las EMs y mejorar la adherencia a la TARV en PVIH con EMs.

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Acknowledgements

We would like to thank all study participants and the personnel at the Colorado Antiviral Pharmacology Laboratory for their invaluable assistance and support of this study. We would also like to thank the director of the UCH-HIV program (Steven Johnson, MD), the medical assistants (Nancy Olague, Brittany Limon, Ariel Cates, Maureen Sullivan and Missy Sorrell) and the nursing staff (Joslyn Axinn, Jackie Deavers, and Ann Czyz) at the UCH-IDGP for their invaluable contributions and support of this study.

Funding

Funding was provided through the National Institutes of Health (K23 AI104315 to J.C.M.; R01 AI122298 to P.L.A.; R56 MH117131-01 to C.D.S.). C.D.S. has received Ryan White funding. P.L.A., J.J.K., and L.R.B. have received research funding from Gilead Sciences, paid to their institution. J.J.K. has also received research funding from Janssen Therapeutics and ViiV Healthcare, paid to their institution.

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Authors and Affiliations

  1. Division of Infectious Diseases, Department of Medicine, School of Medicine, University of Colorado-Anschutz Medical Campus, 12700 E. 19th Ave., B168, Aurora, CO, 80045, USA

    Ryan P. Coyle & Jose R. Castillo-Mancilla

  2. Department of Psychiatry, School of Medicine, University of Colorado-Anschutz Medical Campus, Aurora, CO, 80045, USA

    Christopher D. Schneck

  3. Department of Biostatistics and Informatics, Colorado School of Public Health, University of Colorado-Anschutz Medical Campus, Aurora, CO, USA

    Mary Morrow & Samantha Mawhinney

  4. Duke University Hospital, Durham, NC, USA

    Stacey S. Coleman

  5. Division of Infectious Diseases, Denver Health Medical Center, Denver, CO, USA

    Edward M. Gardner

  6. Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado-Anschutz Medical Campus, Aurora, CO, USA

    Jia-Hua Zheng, Lucas Ellison, Lane R. Bushman, Jennifer J. Kiser & Peter L. Anderson

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  1. Ryan P. Coyle
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Correspondence to Jose R. Castillo-Mancilla.

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Conflict of interest

No conflicts of interest were reported from all remaining authors. Each author has submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts of interest that the editors consider relevant to the content of the manuscript have been disclosed.

Ethical Approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This study was approved by the Colorado Multiple Institutional Review Board (COMIRB; protocol 13-2104) and was registered at ClinicalTrials.gov (NCT02012621).

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Coyle, R.P., Schneck, C.D., Morrow, M. et al. Engagement in Mental Health Care is Associated with Higher Cumulative Drug Exposure and Adherence to Antiretroviral Therapy. AIDS Behav 23, 3493–3502 (2019). https://doi.org/10.1007/s10461-019-02441-8

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