RESEARCH ARTICLE
High Current CD4+ T Cell Count Predicts Suboptimal Adherence to Antiretroviral Therapy Alexander O. Pasternak1*, Marijn de Bruin2, Margreet Bakker1, Ben Berkhout1☯, Jan M. Prins3☯ 1 Laboratory of Experimental Virology, Department of Medical Microbiology, Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center of the University of Amsterdam, Amsterdam, The Netherlands, 2 Health Psychology Group, Institute of Applied Health Sciences, University of Aberdeen, Aberdeen, United Kingdom, 3 Department of Internal Medicine, Division of Infectious Diseases, Academic Medical Center of the University of Amsterdam, Amsterdam, The Netherlands ☯ These authors contributed equally to this work. * [email protected]
Abstract OPEN ACCESS Citation: Pasternak AO, de Bruin M, Bakker M, Berkhout B, Prins JM (2015) High Current CD4+ T Cell Count Predicts Suboptimal Adherence to Antiretroviral Therapy. PLoS ONE 10(10): e0140791. doi:10.1371/journal.pone.0140791 Editor: Jason F Okulicz, Infectious Disease Service, UNITED STATES Received: September 10, 2014 Accepted: September 30, 2015 Published: October 15, 2015 Copyright: © 2015 Pasternak et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability Statement: All relevant data are within the paper. Funding: A.O.P. is financially supported by the Dutch AIDS Fonds (http://www.aidsfonds.nl/), grant nrs. 2011020 and 2012025. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
High levels of adherence to antiretroviral therapy (ART) are necessary for achieving and maintaining optimal virological suppression, as suboptimal adherence leads to therapy failure and disease progression. It is well known that adherence to ART predicts therapy response, but it is unclear whether clinical outcomes of ART predict adherence. To examine the predictive power of current CD4+ T cell count for adherence of HIV-infected individuals to ART, we performed a cross-sectional analysis of 133 Dutch HIV patients with electronically measured adherence. In a multivariate analysis adjusting for a number of sociodemographic and clinical variables, high current CD4+ T cell count (>660 cells/mm3) was most strongly associated with lower adherence to ART (assessed as a continuous variable) during a two-month period immediately following the measurements of variables (P = 0.008). The twice-per-day (versus once-per-day) dosing regimen was also significantly associated with lower adherence (P = 0.014). In a second multivariate analysis aimed at determining the predictors of suboptimal (6 months on ART), started antiretroviral treatment in 1996 or later, and had no uncontrolled psychiatric or drug addiction problems that would prevent them from being able to comply with the study procedures (patients with such problems constitute an extremely small part of our patient population: out of 348 screened patients, 5 and 7 patients were not approached because of severe psychological and drug addiction problems, respectively). Since the nurses preferred to apply this new intervention initially without the additional challenge of language and/or cultural barriers, the trial was focused on native Dutch patients (the main patient population in the Netherlands). The study was approved by the Medical Ethical Committee of the Academic Medical Center, and all patients provided written informed consent. The study has been conducted in accordance with the ethical principles in the Declaration of Helsinki. The time period analyzed in the current study corresponds to a two-month adherence monitoring period between patient inclusion and randomization [11]. Besides measuring adherence, no interventions took place during this period. The subsequent group allocation and adherence interventions could not influence the results of the present study and are not reported here. The following sociodemographic and clinical variables were collected at inclusion: age, gender, education level, current employment, ART regimen, dosing regimen, time on ART, time on ART with undetectable plasma viral load, current CD4+ T cell count, nadir CD4+ T cell count, and current plasma viral load detectability. Adherence was measured electronically using MEMS-cap pill bottles (Aardex, Switzerland) during two-month periods
PLOS ONE | DOI:10.1371/journal.pone.0140791 October 15, 2015
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ART Adherence and CD4+ T Cell Count
immediately following the assessment of variables. MEMS-cap pill bottles recorded the moments of bottle opening electronically. Adherence as measured by MEMS was defined as the percentage of prescribed doses actually taken during the assessment period, and was calculated by dividing the number of times the pill bottle had been opened by the number of times it should have been opened, multiplied by 100. Explanatory power of the sociodemographic and clinical variables was examined both for adherence as a continuous variable and for
High Current CD4+ T Cell Count Predicts Suboptimal Adherence to Antiretroviral Therapy Alexander O. Pasternak1*, Marijn de Bruin2, Margreet Bakker1, Ben Berkhout1☯, Jan M. Prins3☯ 1 Laboratory of Experimental Virology, Department of Medical Microbiology, Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center of the University of Amsterdam, Amsterdam, The Netherlands, 2 Health Psychology Group, Institute of Applied Health Sciences, University of Aberdeen, Aberdeen, United Kingdom, 3 Department of Internal Medicine, Division of Infectious Diseases, Academic Medical Center of the University of Amsterdam, Amsterdam, The Netherlands ☯ These authors contributed equally to this work. * [email protected]
Abstract OPEN ACCESS Citation: Pasternak AO, de Bruin M, Bakker M, Berkhout B, Prins JM (2015) High Current CD4+ T Cell Count Predicts Suboptimal Adherence to Antiretroviral Therapy. PLoS ONE 10(10): e0140791. doi:10.1371/journal.pone.0140791 Editor: Jason F Okulicz, Infectious Disease Service, UNITED STATES Received: September 10, 2014 Accepted: September 30, 2015 Published: October 15, 2015 Copyright: © 2015 Pasternak et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability Statement: All relevant data are within the paper. Funding: A.O.P. is financially supported by the Dutch AIDS Fonds (http://www.aidsfonds.nl/), grant nrs. 2011020 and 2012025. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
High levels of adherence to antiretroviral therapy (ART) are necessary for achieving and maintaining optimal virological suppression, as suboptimal adherence leads to therapy failure and disease progression. It is well known that adherence to ART predicts therapy response, but it is unclear whether clinical outcomes of ART predict adherence. To examine the predictive power of current CD4+ T cell count for adherence of HIV-infected individuals to ART, we performed a cross-sectional analysis of 133 Dutch HIV patients with electronically measured adherence. In a multivariate analysis adjusting for a number of sociodemographic and clinical variables, high current CD4+ T cell count (>660 cells/mm3) was most strongly associated with lower adherence to ART (assessed as a continuous variable) during a two-month period immediately following the measurements of variables (P = 0.008). The twice-per-day (versus once-per-day) dosing regimen was also significantly associated with lower adherence (P = 0.014). In a second multivariate analysis aimed at determining the predictors of suboptimal (6 months on ART), started antiretroviral treatment in 1996 or later, and had no uncontrolled psychiatric or drug addiction problems that would prevent them from being able to comply with the study procedures (patients with such problems constitute an extremely small part of our patient population: out of 348 screened patients, 5 and 7 patients were not approached because of severe psychological and drug addiction problems, respectively). Since the nurses preferred to apply this new intervention initially without the additional challenge of language and/or cultural barriers, the trial was focused on native Dutch patients (the main patient population in the Netherlands). The study was approved by the Medical Ethical Committee of the Academic Medical Center, and all patients provided written informed consent. The study has been conducted in accordance with the ethical principles in the Declaration of Helsinki. The time period analyzed in the current study corresponds to a two-month adherence monitoring period between patient inclusion and randomization [11]. Besides measuring adherence, no interventions took place during this period. The subsequent group allocation and adherence interventions could not influence the results of the present study and are not reported here. The following sociodemographic and clinical variables were collected at inclusion: age, gender, education level, current employment, ART regimen, dosing regimen, time on ART, time on ART with undetectable plasma viral load, current CD4+ T cell count, nadir CD4+ T cell count, and current plasma viral load detectability. Adherence was measured electronically using MEMS-cap pill bottles (Aardex, Switzerland) during two-month periods
PLOS ONE | DOI:10.1371/journal.pone.0140791 October 15, 2015
2 / 11
ART Adherence and CD4+ T Cell Count
immediately following the assessment of variables. MEMS-cap pill bottles recorded the moments of bottle opening electronically. Adherence as measured by MEMS was defined as the percentage of prescribed doses actually taken during the assessment period, and was calculated by dividing the number of times the pill bottle had been opened by the number of times it should have been opened, multiplied by 100. Explanatory power of the sociodemographic and clinical variables was examined both for adherence as a continuous variable and for
