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      Rates and predictors of attrition among children on antiretroviral therapy in Ethiopia: A prospective cohort study

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          Abstract

          Introduction

          Attrition from antiretroviral therapy (ART) programmes is a critical challenge among children receiving care in resource-limited settings. Our objective was to determine the rates and predictors of attrition among children on ART in Ethiopia.

          Methods

          Between December 2014 and September 2016, we conducted a prospective cohort study in eight health facilities in Ethiopia. Eligibility criteria included age 3 months–14 years; being on ART for not more than a month. Outcome was attrition due to death and/or loss to follow-up. Predictor variables were child clinical and socio-demographic characteristics, and caregiver socio-demographic characteristics. We used Cox Regression analyses to examine the association between predictors and outcome.

          Results

          Of 309 children, 304 were included, 52% were male. Their median age was 9 years (Inter-quartile range, IQR, 6–12). At ART initiation, their median CD4 was 362 cells/mm 3 (IQR 231–499); and 74.3% had WHO stage 1 or 2 disease. During 287.7 person-years of observation (PYO), 24 attritions were recorded, yielding an attrition rate of 8.3 per 100 PYO (95% CI 5.4–12.1). Of these, six children were reported dead, leading to a mortality rate of 2.1 per 100 PYO (95% CI 0.8–4.3). Eighteen were lost to follow-up (LTFU) leading to LTFU rate of 6.26 per 100 PYO (95% CI: 3.83–9.70). The majority, 14 (58%) of attrition occurred during the first six months of treatment.

          Age below three years [aHR] = 5.14 (95% CI: 2.07–12.96), rural residence (aHR = 3.97, 95% CI: 1.34–11.78) and baseline Hgb in g/dl < 10 g/dl [aHR] = 5.68 (95% CI: 2.03–6.23) predicted higher risk of attrition. Baseline Hgb < 10 g/dl (aHR = 16.63, 95% CI: 1.64–168.4) and WHO stage III or IV (aHR = 12.25, 95% CI: 1.26–119.05) predicted the death of the child. Higher attrition was documented among children of both biological parents alive and biologically related close family caregivers.

          Conclusion

          Younger children, those from rural areas, and children with anaemia were at higher risk of attrition, especially during the early months of treatment, and therefore should be prioritized during treatment follow-up. Further studies should examine underlying reasons for higher attrition.

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          Most cited references8

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          Retention of HIV-Infected Children in the First 12 Months of Anti-Retroviral Therapy and Predictors of Attrition in Resource Limited Settings: A Systematic Review

          Current UNAIDS goals aimed to end the AIDS epidemic set out to ensure that 90% of all people living with HIV know their status, 90% initiate and continue life-long anti-retroviral therapy (ART), and 90% achieve viral load suppression. In 2014 there were an estimated 2.6 million children under 15 years of age living with HIV, of which only one-third were receiving ART. Little literature exists describing retention of HIV-infected children in the first year on ART. We conducted a systematic search for English language publications reporting on retention of children with median age at ART initiation less than ten years in resource limited settings. The proportion of children retained in care on ART and predictors of attrition were identified. Twelve studies documented retention at one year ranging from 71–95% amongst 31877 African children. Among the 5558 children not retained, 4082 (73%) were reported as lost to follow up (LFU) and 1476 (27%) were confirmed to have died. No studies confirmed the outcomes of children LFU. Predictors of attrition included younger age, shorter duration of time on ART, and severe immunosuppression. In conclusion, significant attrition occurs in children in the first 12 months after ART initiation, the majority attributed to LFU, although true outcomes of children labeled as LFU are unknown. Focused efforts to ensure retention and minimize early mortality are needed as universal ART for children is scaled up.
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            Predictors of mortality among children on Antiretroviral Therapy at a referral hospital, Northwest Ethiopia: A retrospective follow up study

            Background An estimated 2.5 million children were living with HIV/AIDS at the end of 2009, 2.3 million (92%) in sub-Saharan Africa. Without treatment, a third of children with HIV will die of AIDS before their first birthday, half dying before two years of age. Hence, this study aimed to assess magnitude and predictors of mortality among children on Antiretroviral Therapy (ART) at a referral hospital in North-West Ethiopia. Methods Institution based retrospective follow up study was carried out among HIV-positive children from January 1st, 2006 - March 31st, 2011. Information on relevant variables was collected from patients’ charts and registries. Life table was used to estimate the cumulative survival of children. Log rank tests were employed to compare survival between the different categories of the explanatory variables. Multivariate Cox proportional hazards model was fitted to identify predictors of mortality. Results A total of 549 records were included in the analysis. The mean age at initiation of treatment was 6.35 ±3.78 SD years. The median follow up period was 22 months. At the end of the follow up, 41(7.5%) were dead and 384(69.9%) were alive. Mortality was 4.0 deaths per 100 child-years of follow-up period. The cumulative probabilities of survival at 3, 6, 12, 24, and 60 months of ART were 0.96, 0.94, 0.93, 0.92 and 0.83 respectively. Majority (90.2%) of the deaths occurred within the first year of treatment. Absence of cotrimoxazole preventive therapy (adjusted hazard ratio [AHR] = 4.74, 95% CI: 2.17, 10.34), anaemia (haemoglobin level < 10gm/dl) (AHR=2.44, 95% CI: 1.26, 4.73), absolute CD4 cell count below the threshold for severe immunodeficiency (AHR=2.24, 95% CI: 1.07, 4.69) and delayed or regressing developmental milestones at baseline (AHR=6.31, 95% CI: 2.52, 15.83) were predictors of mortality. Conclusions There was a high rate of early mortality. Hence, starting ART very early reduces disease progression and early mortality; close follow up of all children of HIV-positive mothers is recommended to make the diagnosis and start treatment at an earlier time before they develop severe immunodeficiency.
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              Retention in care among HIV-positive patients initiating second-line antiretroviral therapy: a retrospective study from an Ethiopian public hospital clinic

              Background Access to second-line antiretroviral therapy (ART) for HIV-positive patients remains limited in sub-Saharan Africa. Furthermore, outcomes of second-line ART may be compromised by mortality and loss to follow-up (LTFU). Objective To determine retention in care among patients receiving second-line ART in a public hospital in Ethiopia, and to investigate factors associated with LTFU among adults and adolescents. Design HIV-positive persons with documented change of first-line ART to a second-line regimen were retrospectively identified from hospital registers, and data were collected at the time of treatment change and subsequent clinic visits. Baseline variables for adults and adolescents were analyzed using multivariate Cox proportional hazards models comparing subjects remaining in care and those LTFU (defined as a missed appointment of ≥90 days). Results A total of 383 persons had started second-line ART (330 adults/adolescents; 53 children) and were followed for a median of 22.2 months (the total follow-up time was 906 person years). At the end of study follow-up, 80.5% of patients remained in care (adults and adolescents 79.8%; children 85.7%). In multivariate analysis, LTFU among adults and adolescents was associated with a baseline CD4 cell count <100 cells/mm3 and a first-line regimen failure that was not confirmed by HIV RNA testing. Conclusions Although retention in care during second-line ART in this cohort was satisfactory, and similar to that reported from first-line ART programs in Ethiopia, our findings suggest the benefit of earlier recognition of patients with first-line ART failure and confirmation of suspected treatment failure by viral load testing.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Project administrationRole: ResourcesRole: SoftwareRole: SupervisionRole: ValidationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Formal analysisRole: Funding acquisitionRole: MethodologyRole: Project administrationRole: ResourcesRole: SupervisionRole: Writing – review & editing
                Role: Formal analysisRole: MethodologyRole: SupervisionRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: SoftwareRole: SupervisionRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                6 February 2018
                2018
                : 13
                : 2
                : e0189777
                Affiliations
                [1 ] Department of Health Sciences, Faculty of Medicine, Lund University, Sweden
                [2 ] Management Sciences for Health, Addis Ababa, Ethiopia
                National and Kapodistrian University of Athens, GREECE
                Author notes

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

                Author information
                http://orcid.org/0000-0002-8370-2571
                Article
                PONE-D-17-25959
                10.1371/journal.pone.0189777
                5800538
                29408897
                a95e46dd-52b9-4d55-9244-a469345b0930
                © 2018 Biru 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
                : 10 July 2017
                : 12 November 2017
                Page count
                Figures: 2, Tables: 4, Pages: 13
                Funding
                This study was supported by the Swedish Research Council [grant number 521-2013-2633], The Swedish Research Council for Health, Working Life and Welfare [grant number 2013-2094] and SIDA [grant number 348-2011-7394]. The support was received by I. Hallström.
                Categories
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                Biology and Life Sciences
                Immunology
                Vaccination and Immunization
                Antiviral Therapy
                Antiretroviral Therapy
                Medicine and Health Sciences
                Immunology
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                All relevant data are available at Dryad Digital Repository: https://doi.org/10.5061/dryad.12g6g.

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