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      Lamivudine Concentration in Hair and Prediction of Virologic Failure and Drug Resistance among HIV Patients Receiving Free ART in China

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          Abstract

          Background

          The assessment of adherence to antiretroviral therapy (ART) is important in order to predict treatment outcomes. Lamivudine (3TC) is one of the most widely used NRTIs in China, but its concentrations in hair and association with virologic failure and drug resistance have not been studied.

          Methods

          We conducted a cross-sectional survey to investigate 3TC concentrations in hair as a predictor of virologic failure and drug resistance among HIV patients receiving free ART. We also compared the capacity of hair 3TC concentrations with self-reported adherence in predicting virologic responses. Hair 3TC concentrations were detected through the LC-MS/MS system.

          Results

          In patients without HIV drug resistance (HIVDR), with a threshold hair 3TC concentration of 260 ng/g, the sensitivity and specificity in predicting virologic suppression were 76.9% and 89.9%, respectively. Some factors, including CD4 + cell counts, initial treatment regimens with 3TC, and current regimens with second-line drugs, influenced the association between hair 3TC concentrations and virologic suppression. In patients who experienced virologic failure with HIVDR, with a threshold of 180 ng/g, the sensitivity and specificity were 70.0% and 74.4%, respectively. Hair 3TC concentrations had higher sensitivity and specificity in predicting virologic failure and drug resistance than self-reported adherence.

          Conclusions

          The hair 3TC concentration was a stronger indicator than self-reported adherence in predicting virologic failure and drug resistance in HIV patients receiving free ART.

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          Most cited references33

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          Antiretroviral therapy adherence and viral suppression in HIV-infected drug users: comparison of self-report and electronic monitoring.

          To compare electronically monitored (MEMS) with self-reported adherence in drug users, including the impact of adherence on HIV load, we conducted a 6-month observational study of 67 antiretroviral-experienced current and former drug users. Adherence (percentage of doses taken as prescribed) was calculated for both the day and the week preceding each of 6 research visits. Mean self-reported 1-day adherence was 79% (median, 86%), and mean self-reported 1-week adherence was 78% (median, 85%). Mean MEMS 1-day adherence was 57% (median, 52%), and mean MEMS 1-week adherence was 53% (median, 49%). One-day and 1-week estimates were highly correlated (r>.8 for both measures). Both self-reported and MEMS adherence were correlated with concurrent HIV load (r=.43-.60), but the likelihood of achieving virologic suppression was greater if MEMS adherence was high than if self-reported adherence was high. We conclude that self-reported adherence is higher than MEMS adherence, but a strong relationship exists between both measures and virus load. However, electronic monitoring is more sensitive than self-report for the detection of nonadherence and should be used in adherence intervention studies.
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            A comparison study of multiple measures of adherence to HIV protease inhibitors.

            Poor adherence to HIV protease inhibitors may compromise the effectiveness of treatment. Few studies have compared methods for measuring adherence or have related adherence measures to a clinical outcome. To examine the relationship among a composite score of adherence, the three primary measures of adherence, and HIV virologic response. Longitudinal cohort study. Public HIV clinic. 108 HIV-infected adults receiving protease inhibitors or non-nucleoside reverse transcriptase inhibitors who were monitored for 666 monthly intervals. Medication Event Monitoring System (MEMS), pill count, and interview combined into a composite adherence score (CAS), and HIV viral load. Mean antiretroviral adherence differed by adherence measure (MEMS, 0.63; pill count, 0.83; interview, 0.93; and CAS, 0.76). Composite adherence score decreased significantly over time. Composite adherence score, MEMS values, pill values, and interview values were statistically significantly associated with achievement of an undetectable viral load within 6 months of initiating therapy. Composite adherence score showed the strongest predictive relationship (odds ratios for a 10% increase in adherence for CAS, MEMS, pill count, and interview, respectively, were 1.26 [95% CI, 1.16 to 1.37], 1.13 [CI, 1.06 to 1.21], 1.10 [CI, 1.02 to 1.19], and 1.35 [CI, 0.94 to 1.94]). Different measures applied to the same patient suggest different levels of adherence. Adherence may be underestimated by MEMS and overestimated by pill count and interview. A summary measure combining several measures is more strongly related to a clinical response, but more practical measurement methods are needed for clinical use.
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              Practical and conceptual challenges in measuring antiretroviral adherence.

              Accurate measurement of antiretroviral adherence is essential for targeting and rigorously evaluating interventions to improve adherence and prevent viral resistance. Across diseases, medication adherence is an individual, complex, and dynamic human behavior that presents unique measurement challenges. Measurement of medication adherence is further complicated by the diversity of available measures, which have different utility in clinical and research settings. Limited understanding of how to optimize existing adherence measures has hindered progress in adherence research in HIV and other diseases. Although self-report is the most widely used adherence measure and the most promising for use in clinical care and resource-limited settings, adherence researchers have yet to develop evidence-based standards for self-reported adherence. In addition, the use of objective measures, such as electronic drug monitoring or pill counts, is limited by poor understanding of the source and magnitude of error biasing these measures. To address these limitations, research is needed to evaluate methods of combining information from different measures. The goals of this review are to describe the state of the science of adherence measurement, to discuss the advantages and disadvantages of common adherence measurement methods, and to recommend directions for improving antiretroviral adherence measurement in research and clinical care.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                27 April 2016
                2016
                : 11
                : 4
                : e0154421
                Affiliations
                [1 ]State Key Laboratory of Infectious Disease Prevention and Control (SKLID), National Center for AIDS/STD Control (NCAIDS) and Prevention, Chinese Center for Disease Control and Prevention (China CDC), Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Beijing, China
                [2 ]Henan Center for Disease Control and Prevention, Zhenzhou, Henan Province, China
                [3 ]Anhui Center for Disease Control and Prevention, Hefei, Anhui Province, China
                [4 ]Zhejiang Center for Disease Control and Prevention, Hangzhou, Zhejiang Province, China
                Shanghai Medical College, Fudan University, CHINA
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: HX YHR YMS. Performed the experiments: XHP BS ZW JJW JFZ. Analyzed the data: JY JH. Contributed reagents/materials/analysis tools: YHR LJL. Wrote the paper: JL JY.

                Article
                PONE-D-15-53356
                10.1371/journal.pone.0154421
                4847920
                27119346
                5fda1efa-0ce7-4d9b-a7fb-d3f70a9e30ea
                © 2016 Yan 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.

                History
                : 5 January 2016
                : 13 April 2016
                Page count
                Figures: 1, Tables: 3, Pages: 12
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/501100002855, Ministry of Science and Technology of the People's Republic of China;
                Award ID: 2012ZX10001-002 and 2009DFB30420
                Award Recipient :
                Funded by: the Chinese State Key Laboratory of Infectious Disease Develop Grant, and the International Development Research Center of Canada
                Award ID: grant #104519-010
                Award Recipient :
                This study was supported by grants from the Ministry of Science and Technology of China (2012ZX10001-002 and 2009DFB30420), the Chinese State Key Laboratory of Infectious Disease Develop Grant, and the International Development Research Center of Canada (grant #104519-010). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
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                Biology and Life Sciences
                Microbiology
                Microbial Control
                Antimicrobial Resistance
                Medicine and Health Sciences
                Pharmacology
                Antimicrobial Resistance
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