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      Effectiveness of Patient Adherence Groups as a Model of Care for Stable Patients on Antiretroviral Therapy in Khayelitsha, Cape Town, South Africa

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          Abstract

          Background

          Innovative models of care are required to cope with the ever-increasing number of patients on antiretroviral therapy in the most affected countries. This study, in Khayelitsha, South Africa, evaluates the effectiveness of a group-based model of care run predominantly by non-clinical staff in retaining patients in care and maintaining adherence.

          Methods and Findings

          Participation in “adherence clubs” was offered to adults who had been on ART for at least 18 months, had a current CD4 count >200 cells/ml and were virologically suppressed. Embedded in an ongoing cohort study, we compared loss to care and virologic rebound in patients receiving the intervention with patients attending routine nurse-led care from November 2007 to February 2011. We used inverse probability weighting to estimate the intention-to-treat effect of adherence club participation, adjusted for measured baseline and time-varying confounders. The principal outcome was the combination of death or loss to follow-up. The secondary outcome was virologic rebound in patients who were virologically suppressed at study entry. Of 2829 patients on ART for >18 months with a CD4 count above 200 cells/µl, 502 accepted club participation. At the end of the study, 97% of club patients remained in care compared with 85% of other patients. In adjusted analyses club participation reduced loss-to-care by 57% (hazard ratio [HR] 0.43, 95% CI = 0.21–0.91) and virologic rebound in patients who were initially suppressed by 67% (HR 0.33, 95% CI = 0.16–0.67).

          Discussion

          Patient adherence groups were found to be an effective model for improving retention and documented virologic suppression for stable patients in long term ART care. Out-of-clinic group-based models facilitated by non-clinical staff are a promising approach to assist in the long-term management of people on ART in high burden low or middle-income settings.

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          Most cited references15

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          Marginal structural models to estimate the causal effect of zidovudine on the survival of HIV-positive men.

          Standard methods for survival analysis, such as the time-dependent Cox model, may produce biased effect estimates when there exist time-dependent confounders that are themselves affected by previous treatment or exposure. Marginal structural models are a new class of causal models the parameters of which are estimated through inverse-probability-of-treatment weighting; these models allow for appropriate adjustment for confounding. We describe the marginal structural Cox proportional hazards model and use it to estimate the causal effect of zidovudine on the survival of human immunodeficiency virus-positive men participating in the Multicenter AIDS Cohort Study. In this study, CD4 lymphocyte count is both a time-dependent confounder of the causal effect of zidovudine on survival and is affected by past zidovudine treatment. The crude mortality rate ratio (95% confidence interval) for zidovudine was 3.6 (3.0-4.3), which reflects the presence of confounding. After controlling for baseline CD4 count and other baseline covariates using standard methods, the mortality rate ratio decreased to 2.3 (1.9-2.8). Using a marginal structural Cox model to control further for time-dependent confounding due to CD4 count and other time-dependent covariates, the mortality rate ratio was 0.7 (95% conservative confidence interval = 0.6-1.0). We compare marginal structural models with previously proposed causal methods.
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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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              Methotrexate and mortality in patients with rheumatoid arthritis: a prospective study.

              Methotrexate is the most frequent choice of disease-modifying antirheumatic therapy for rheumatoid arthritis. Although results of studies have shown the efficacy of such drugs, including methotrexate, on rheumatoid arthritis morbidity measures, their effect on mortality in patients with the disease remains unknown. Our aim was to prospectively assess the effect on mortality of methotrexate in a cohort of patients with rheumatoid arthritis. Our cohort included 1240 patients with rheumatoid arthritis seen at the Wichita Arthritis Center, an outpatient rheumatology facility. Patients' details were entered into a computerised database at the time of their first clinic visit. We also obtained and recorded demographic, clinical, laboratory, and self-reported data at each follow-up visit (average interval 3.5 months). We estimated the mortality hazard ratio of methotrexate with a marginal structural Cox proportional hazards model. 191 individuals died during follow-up. Patients who began treatment with methotrexate (n=588) had worse prognostic factors for mortality. After adjustment for this confounding by indication, the mortality hazard ratio for methotrexate use compared with no methotrexate use was 0.4 (95% CI 0.2-0.8). Other conventional disease-modifying antirheumatic drugs did not have a significant effect on mortality. The hazard ratio of methotrexate use for cardiovascular death was 0.3 (0.2-0.7), whereas that for non-cardiovascular deaths was 0.6 (0.2-1.2). Our data indicate that methotrexate may provide a substantial survival benefit, largely by reducing cardiovascular mortality. This survival benefit of methotrexate would set a standard against which new disease-modifying antirheumatic drugs could be compared.
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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, USA )
                1932-6203
                2013
                13 February 2013
                : 8
                : 2
                : e56088
                Affiliations
                [1 ]Centre for Infectious Disease Epidemiology and Research, School of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa
                [2 ]Médecins sans Frontières, Cape Town, South Africa
                [3 ]Khayelitsha Community Health Centre, Department of Health, Provincial Government of the Western Cape, Cape Town, South Africa
                [4 ]Treatment Action Campaign, Cape Town, South Africa
                [5 ]Médecins sans Frontières, Geneva, Switzerland
                [6 ]Departments of Epidemiology and Biostatistics, Harvard School of Public Health, Boston, Massachusetts, United States of America
                [7 ]Division of Health Sciences and Technology, Harvard-Massachusetts Institute of Technology, Boston, Massachusetts, United States of America
                Johns Hopkins Bloomberg School of Public Health, United States of America
                Author notes

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

                Developed the concept and design of the study: MALF AB GVC NF MS. Acquired the data: GVC EG KH NM SM VD. Developed and conducted the analyses: MALF AB MAH. Interpreted the data: MALF GVC EG KH MS NM SM VD NF MAH AB. Wrote the initial manuscript draft: MALF. Critically revised the content, and contributed technical support and conceptual advice: MALF GVC EG KH MS NM SM VD NF MAH AB. Read and approved the final manuscript: MALF GVC EG KH MS NM SM VD NF MAH AB. Guarantor of the paper: MALF.

                [¤]

                Current address: Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, United States of America

                Article
                PONE-D-12-20883
                10.1371/journal.pone.0056088
                3571960
                23418518
                edd3e823-eb5c-478d-8760-f8732fd8ed59
                Copyright @ 2013

                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
                : 10 July 2012
                : 4 January 2013
                Page count
                Pages: 8
                Funding
                MALF was supported by the University of Cape Town with a postdoctoral fellowship (LQFMIG001). AB was partially supported by the National Institute of Allergy and Infectious Diseases (U01AI069924-01). MAH was partly funded by NIH grant R01 AI102634. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Biology
                Microbiology
                Virology
                Antivirals
                Mathematics
                Statistics
                Medicine
                Clinical Research Design
                Cohort Studies
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                Infectious Disease Epidemiology
                Global Health
                Infectious Diseases
                Viral Diseases
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                Retrovirology and HIV immunopathogenesis
                Infectious Disease Control
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                Health Care Quality
                Health Services Research
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                Nursing Science
                Nursing Administration
                Primary Care
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                Socioeconomic Aspects of Health
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