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      Prospective assessment of loss to follow‐up: incidence and associated factors in a cohort of HIV‐positive adults in rural Tanzania

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          Abstract

          Introduction

          Lifelong antiretroviral therapy (ART) improves health outcomes for HIV‐positive individuals, but is jeopardized by irregular clinic attendance and hence poor adherence. Loss to follow‐up (LTFU) is typically defined retrospectively but this may lead to biased inferences. We assessed incidence of and factors associated with LTFU, prospectively and accounting for recurrent LTFU episodes, in the Kilombero and Ulanga Antiretroviral Cohort (KIULARCO) of HIV‐positive persons in rural Tanzania.

          Methods

          We included adults (≥15 years) enrolled in 2005 to 2016, regardless of ART status, with follow‐up through April 2017. LTFU was defined as >60 days late for a scheduled appointment. Participants could experience multiple LTFU episodes. We performed analyses based on the first (prospective) and last (retrospective) events observed during follow‐up, and accounting for recurrent LTFU episodes. Time to LTFU was estimated using cumulative incidence functions. We assessed factors associated with LTFU using cause‐specific proportional hazards, marginal means/rates, and Prentice, Williams and Peterson models.

          Results

          Among 8087 participants (65% female, 60% aged ≥35 years, 42% WHO stage 3/4, and 47% CD4 count <200 cells/mm 3), there were 8140 LTFU episodes, after which there were 2483 (31%) returns to care. One‐year LTFU probabilities were 0.41 (95% confidence interval 0.40, 0.42) and 0.21 (0.20, 0.22) considering the first and last events respectively. Factors associated with LTFU were broadly consistent across different models: being male, younger age, never married, living far from the clinic, not having an HIV‐positive partner, lower BMI, advanced WHO stage, not having tuberculosis, and shorter time since ART initiation. Associations between LTFU and pregnancy, CD4 count, and enrolment year depended on the analysis approach.

          Conclusions

          LTFU episodes were common and prompt tracing efforts are urgently needed. We identified socio‐demographic and clinical characteristics associated with LTFU that can be used to target tracing efforts and to help inform the design of appropriate interventions. Incidence of and risk factors for LTFU differed based on the LTFU definition applied, highlighting the importance of appropriately accounting for recurrent LTFU episodes. We recommend using a prospective definition of LTFU combined with recurrent event analyses in cohorts where repeated interruptions in care are common.

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          Most cited references29

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          Understanding reasons for and outcomes of patients lost to follow-up in antiretroviral therapy programs in Africa through a sampling-based approach.

          Losses to follow-up after initiation of antiretroviral therapy (ART) are common in Africa and are a considerable obstacle to understanding the effectiveness of nascent treatment programs. We sought to characterize, through a sampling-based approach, reasons for and outcomes of patients who become lost to follow-up. Cohort study. We searched for and interviewed a representative sample of lost patients or close informants in the community to determine reasons for and outcomes among lost patients. Three thousand six hundred twenty-eight HIV-infected adults initiated ART between January 1, 2004 and September 30, 2007 in Mbarara, Uganda. Eight hundred twenty-nine became lost to follow-up (cumulative incidence at 1, 2, and 3 years of 16%, 30%, and 39%). We sought a representative sample of 128 lost patients in the community and ascertained vital status in 111 (87%). Top reasons for loss included lack of transportation or money and work/child care responsibilities. Among the 111 lost patients who had their vital status ascertained through tracking, 32 deaths occurred (cumulative 1-year incidence 36%); mortality was highest shortly after the last clinic visit. Lower pre-ART CD4 T-cell count, older age, low blood pressure, and a central nervous system syndrome at the last clinic visit predicted deaths. Of patients directly interviewed, 83% were in care at another clinic and 71% were still using ART. Sociostructural factors are the primary reasons for loss to follow-up. Outcomes among the lost are heterogeneous: both deaths and transfers to other clinics were common. Tracking a sample of lost patients is an efficient means for programs to understand site-specific reasons for and outcomes among patients lost to follow-up.
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            Modelling recurrent events: a tutorial for analysis in epidemiology.

            In many biomedical studies, the event of interest can occur more than once in a participant. These events are termed recurrent events. However, the majority of analyses focus only on time to the first event, ignoring the subsequent events. Several statistical models have been proposed for analysing multiple events. In this paper we explore and illustrate several modelling techniques for analysis of recurrent time-to-event data, including conditional models for multivariate survival data (AG, PWP-TT and PWP-GT), marginal means/rates models, frailty and multi-state models. We also provide a tutorial for analysing such type of data, with three widely used statistical software programmes. Different approaches and software are illustrated using data from a bladder cancer project and from a study on lower respiratory tract infection in children in Brazil. Finally, we make recommendations for modelling strategy selection for analysis of recurrent event data.
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              Outcomes of Patients Lost to Follow-up in African Antiretroviral Therapy Programs: Individual Patient Data Meta-analysis

              Retention on antiretrovirals is of concern in Africa. We analyzed outcomes in patients lost to follow-up: at 4 years after last contact, 22% had died, 23% had stopped therapy, 15% were in another clinic, and 32% could not be found.
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                Author and article information

                Contributors
                fiona.vanobberghen@swisstph.ch
                Journal
                J Int AIDS Soc
                J Int AIDS Soc
                10.1002/(ISSN)1758-2652
                JIA2
                Journal of the International AIDS Society
                John Wiley and Sons Inc. (Hoboken )
                1758-2652
                03 March 2020
                March 2020
                : 23
                : 3 ( doiID: 10.1002/jia2.v23.3 )
                : e25460
                Affiliations
                [ 1 ] Ifakara Health Institute Ifakara Tanzania
                [ 2 ] Swiss Tropical and Public Health Institute Basel Switzerland
                [ 3 ] University of Basel Basel Switzerland
                [ 4 ] Department of Infectious Diseases and Hospital Epidemiology Department of Clinical Research University Hospital Basel Basel Switzerland
                [ 5 ] USAID Boresha Afya Morogoro Tanzania
                Author notes
                [*] [* ] Corresponding author: Fiona Vanobberghen; Swiss Tropical and Public Health Institute, Socinstrasse 55, Basel, Switzerland. Tel: +41 61 284 87 16. ( fiona.vanobberghen@ 123456swisstph.ch )

                [†]

                Membership of the KIULARCO Study Group is provided in the Acknowledgements.

                Author information
                https://orcid.org/0000-0001-7075-9803
                https://orcid.org/0000-0002-8908-0953
                Article
                JIA225460
                10.1002/jia2.25460
                7054631
                32128998
                56222054-9441-4dcb-ac5f-35623f8fc220
                © 2020 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 17 September 2019
                : 09 January 2020
                : 22 January 2020
                Page count
                Figures: 2, Tables: 2, Pages: 10, Words: 9670
                Funding
                Funded by: Ministry of Health and Social Welfare of the Government of Tanzania
                Funded by: Government of the Canton of Basel, Switzerland
                Funded by: Swiss Tropical and Public Health Institute, Basel, Switzerland
                Funded by: Ifakara Health Institute, Tanzania
                Funded by: USAID Boresha Afya
                Categories
                Research Article
                Research Articles
                Custom metadata
                2.0
                March 2020
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.7.6.1 mode:remove_FC converted:04.03.2020

                Infectious disease & Microbiology
                lost to follow‐up,recurrent events,hiv infections,tanzania,cohort,proportional hazards models

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