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      Excellent Adherence to Antiretrovirals in HIV+ Zambian Children Is Compromised by Disrupted Routine, HIV Nondisclosure, and Paradoxical Income Effects

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          Abstract

          Introduction

          A better understanding of pediatric antiretroviral therapy (ART) adherence in sub-Saharan Africa is necessary to develop interventions to sustain high levels of adherence.

          Methodology/Principal Findings

          Adherence among 96 HIV-infected Zambian children (median age 6, interquartile range [IQR] 2,9) initiating fixed-dose combination ART was measured prospectively (median 23 months; IQR 20,26) with caregiver report, clinic and unannounced home-based pill counts, and medication event monitoring systems (MEMS). HIV-1 RNA was determined at 48 weeks. Child and caregiver characteristics, socio-demographic status, and treatment-related factors were assessed as predictors of adherence. Median adherence was 97.4% (IQR 96.1,98.4%) by visual analog scale, 94.8% (IQR 86,100%) by caregiver-reported last missed dose, 96.9% (IQR 94.5,98.2%) by clinic pill count, 93.4% (IQR 90.2,96.7%) by unannounced home-based pill count, and 94.8% (IQR 87.8,97.7%) by MEMS. At 48 weeks, 72.6% of children had HIV-1 RNA <50 copies/ml. Agreement among adherence measures was poor; only MEMS was significantly associated with viral suppression (p = 0.013). Predictors of poor adherence included changing residence, school attendance, lack of HIV disclosure to children aged nine to 15 years, and increasing household income.

          Conclusions/Significance

          Adherence among children taking fixed-dose combination ART in sub-Saharan Africa is high and sustained over two years. However, certain groups are at risk for treatment failure, including children with disrupted routines, no knowledge of their HIV diagnosis among older children, and relatively high household income, possibly reflecting greater social support in the setting of greater poverty.

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          Most cited references34

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          Statistical methods for assessing agreement between two methods of clinical measurement.

          In clinical measurement comparison of a new measurement technique with an established one is often needed to see whether they agree sufficiently for the new to replace the old. Such investigations are often analysed inappropriately, notably by using correlation coefficients. The use of correlation is misleading. An alternative approach, based on graphical techniques and simple calculations, is described, together with the relation between this analysis and the assessment of repeatability.
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            Antiretroviral therapy adherence, virologic and immunologic outcomes in adolescents compared with adults in southern Africa.

            To determine adherence to and effectiveness of antiretroviral therapy (ART) in adolescents vs. adults in southern Africa. Observational cohort study. Aid for AIDS, a private sector disease management program in southern Africa. Adolescents (age 11-19 years; n = 154) and adults (n = 7622) initiating ART between 1999 and 2006 and having a viral load measurement within 1 year after ART initiation. Primary: virologic suppression (HIV viral load < or = 400 copies/mL), viral rebound, and CD4 T-cell count at 6, 12, 18, and 24 months after ART initiation. Secondary: adherence assessed by pharmacy refills at 6, 12, and 24 months. Multivariate analyses: loglinear regression and Cox proportional hazards. A significantly smaller proportion of adolescents achieved 100% adherence at each time point (adolescents: 20.7% at 6 months, 14.3% at 12 months, and 6.6% at 24 months; adults: 40.5%, 27.9%, and 20.6% at each time point, respectively; P < 0.01). Patients achieving 100% 12-month adherence were significantly more likely to exhibit virologic suppression at 12 months, regardless of age. However, adolescents achieving virologic suppression had significantly shorter time to viral rebound (adjusted hazard ratio 2.03; 95% confidence interval: 1.31 to 3.13; P < 0.003). Adolescents were less likely to experience long-term immunologic recovery despite initial CD4 T-cell counts comparable to adults. Compared with adults, adolescents in southern Africa are less adherent to ART and have lower rates of virologic suppression and immunologic recovery and a higher rate of virologic rebound after initial suppression. Studies must determine specific barriers to adherence in this population and develop appropriate interventions.
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              Self-report measures of antiretroviral therapy adherence: A review with recommendations for HIV research and clinical management.

              A review of 77 studies employing self-report measures of antiretroviral adherence published 1/1996 through 8/2004 revealed great variety in adherence assessment item content, format, and response options. Recall periods ranged from 2 to 365 days (mode = 7 days). The most common cutoff for optimal adherence was 100% (21/48 studies, or 44%). In 27 of 34 recall periods (79%), self-reported adherence was associated with adherence as assessed with other indirect measures. Data from 57 of 67 recall periods (84%) indicated self-reported adherence was significantly associated with HIV-1 RNA viral load; in 16 of 26 (62%), it was associated with CD4 count. Clearly, the field would benefit from item standardization and a priori definitions and operationalizations of adherence. We conclude that even brief self-report measures of antiretroviral adherence can be robust, and recommend items and strategies for HIV research and clinical management.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2011
                21 April 2011
                : 6
                : 4
                : e18505
                Affiliations
                [1 ]Massachusetts General Hospital Center for Global Health, Boston, Massachusetts, United States of America
                [2 ]Medical Research Council Clinical Trials Unit, London, United Kingdom
                [3 ]University Teaching Hospital, Lusaka, Zambia
                [4 ]Joint Clinical Research Centre, Kampala, Uganda
                Karolinska Institutet, Sweden
                Author notes

                Conceived and designed the experiments: JH AC ASW MT CC DMG DRB. Performed the experiments: MN VM CK DK CC. Analyzed the data: JH AC ASW AF MT DMG DRB. Contributed reagents/materials/analysis tools: CK. Wrote the paper: JH AC ASW MN AF VM CK MT DK CC DMG DRB.

                Article
                PONE-D-11-00329
                10.1371/journal.pone.0018505
                3080873
                21533031
                ae2986fa-6607-4247-937b-f7fa2e381736
                Haberer 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
                : 20 December 2010
                : 2 March 2011
                Page count
                Pages: 8
                Categories
                Research Article
                Biology
                Microbiology
                Virology
                Antivirals
                Medicine
                Drugs and Devices
                Infectious Diseases
                Viral Diseases
                HIV
                HIV diagnosis and management
                Pediatrics
                Social and Behavioral Sciences
                Psychology
                Behavior
                Habits

                Uncategorized
                Uncategorized

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