Browsing by Author "Ballif M"
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Item Correcting mortality estimates among children and youth on antiretroviral therapy in southern Africa: A comparative analysis between a multi-country tracing study and linkage to a health information exchange.(2024-Aug) Nyakato P; Schomaker M; Boulle A; Euvrard J; Wood R; Eley B; Prozesky H; Christ B; Anderegg N; Ayakaka I; Rafael I; Kunzekwenyika C; Moore CB; van Lettow M; Chimbetete C; Mbewe S; Ballif M; Egger M; Yiannoutsos CT; Cornell M; Davies MA; R.M Fairbanks, School of Public Health, Department of Biostatistics, Indiana University, Indianapolis, Indiana, USA.; Centre for Infectious Diseases Research in Zambia, Lusaka, Zambia.; SolidarMed, Pemba, Mozambique.; Centre for Infectious Disease Epidemiology and Research, School of Public Health, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.; Dalla Lana School of Public Health, University of Toronto, Toronto, Canada.; Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.; Newlands Clinic, Harare, Zimbabwe.; SolidarMed, Masvingo, Zimbabwe.; Department of Infectious Diseases, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.; Division of Infectious Diseases, Department of Medicine, University of Stellenbosch and Tygerberg Academic Hospital, Cape Town, South Africa.; Lighthouse Trust Clinic, Lilongwe, Malawi.; SolidarMed, Maseru, Lesotho.; Khayelitsha ART Programme, Cape Town, South Africa.; Western Cape Government: Health and Wellness, Cape Town, South Africa.; Wellcome Centre for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.; Madiro, Toronto, Canada.; Department of Statistics, Ludwig-Maximilians-Universität München, Munich, Germany.; Red Cross War Memorial Children's Hospital and Department of Paediatrics and Child Health, University of Cape Town, Cape Town, South Africa.; Gugulethu HIV Programme and Desmond Tutu HIV Centre, University of Cape Town, Cape Town, South Africa.; Dignitas International, Zomba, Malawi.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)OBJECTIVES: The objective of this study is to assess the outcomes of children, adolescents and young adults with HIV reported as lost to follow-up, correct mortality estimates for children, adolescents and young adults with HIV for unascertained outcomes in those loss to follow-up (LTFU) based on tracing and linkage data separately using data from the International epidemiology Databases to Evaluate AIDS in Southern Africa. METHODS: We included data from two different populations of children, adolescents and young adults with HIV; (1) clinical data from children, adolescents and young adults with HIV aged ≤24 years from Lesotho, Malawi, Mozambique, Zambia and Zimbabwe; (2) clinical data from children, adolescents and young adults with HIV aged ≤14 years from the Western Cape (WC) in South Africa. Outcomes of patients lost to follow-up were available from (1) a tracing study and (2) linkage to a health information exchange. For both populations, we compared six methods for correcting mortality estimates for all children, adolescents and young adults with HIV. RESULTS: We found substantial variations of mortality estimates among children, adolescents and young adults with HIV reported as lost to follow-up versus those retained in care. Ascertained mortality was higher among lost and traceable children, adolescents and young adults with HIV and lower among lost and linkable than those retained in care (mortality: 13.4% [traced] vs. 12.6% [retained-other Southern Africa countries]; 3.4% [linked] vs. 9.4% [retained-WC]). A high proportion of lost to follow-up children, adolescents and young adults with HIV had self-transferred (21.0% and 47.0%) in the traced and linked samples, respectively. The uncorrected method of non-informative censoring yielded the lowest mortality estimates among all methods for both tracing (6.0%) and linkage (4.0%) approaches at 2 years from ART start. Among corrected methods using ascertained data, multiple imputation, incorporating ascertained data (MI(asc.)) and inverse probability weighting with logistic weights were most robust for the tracing approach. In contrast, for the linkage approach, MI(asc.) was the most robust. CONCLUSIONS: Our findings emphasise that lost to follow-up is non-ignorable and both tracing and linkage improved outcome ascertainment: tracing identified substantial mortality in those reported as lost to follow-up, whereas linkage did not identify out-of-facility deaths, but showed that a large proportion of those reported as lost to follow-up were self-transfers.Item Detection and management of drug-resistant tuberculosis in HIV-infected patients in lower-income countries.(2014-Nov) Ballif M; Nhandu V; Wood R; Dusingize JC; Carter EJ; Cortes CP; McGowan CC; Diero L; Graber C; Renner L; Hawerlander D; Kiertiburanakul S; Du QT; Sterling TR; Egger M; Fenner L; Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.; Centre Intégré de Recherches Biocliniques, Abidjan, Côte d'Ivoire.; United States Agency for International Development Academic Model Providing Access to Healthcare, Eldoret, Kenya.; Vanderbilt University School of Medicine, Nashville, Tennessee, USA.; Swiss Tropical and Public Health Institute, University of Basel, Basel, Switzerland.; Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand; Children's Hospital, Ho Chi Minh City, Viet Nam.; Women's Equity in Access to Care & Treatment, Kigali, Rwanda.; Desmond Tutu HIV Centre, University of Cape Town, Cape Town, South Africa.; University of Ghana Medical School, Accra, Ghana.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; University of Chile School of Medicine, Santiago, Chile.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)SETTING: Drug resistance threatens tuberculosis (TB) control, particularly among human immunodeficiency virus (HIV) infected persons. OBJECTIVE: To describe practices in the prevention and management of drug-resistant TB under antiretroviral therapy (ART) programs in lower-income countries. DESIGN: We used online questionnaires to collect program-level data on 47 ART programs in Southern Africa (n = 14), East Africa (n = 8), West Africa (n = 7), Central Africa (n = 5), Latin America (n = 7) and the Asia-Pacific (n = 6 programs) in 2012. Patient-level data were collected on 1002 adult TB patients seen at 40 of the participating ART programs. RESULTS: Phenotypic drug susceptibility testing (DST) was available in 36 (77%) ART programs, but was only used for 22% of all TB patients. Molecular DST was available in 33 (70%) programs and was used in 23% of all TB patients. Twenty ART programs (43%) provided directly observed therapy (DOT) during the entire course of treatment, 16 (34%) during the intensive phase only, and 11 (23%) did not follow DOT. Fourteen (30%) ART programs reported no access to second-line anti-tuberculosis regimens; 18 (38%) reported TB drug shortages. CONCLUSIONS: Capacity to diagnose and treat drug-resistant TB was limited across ART programs in lower-income countries. DOT was not always implemented and drug supplies were regularly interrupted, which may contribute to the global emergence of drug resistance.Item High Unreported Mortality in Children and Youth (<25 Years) Living With HIV Who Were Lost to Care From Antiretroviral Therapy Programs in Southern Africa: Results From a Multicountry Tracing Study.(2022-Dec-15) Nyakato P; Christ B; Anderegg N; Muhairwe J; Jefferys L; van Dijk J; Vinikoor MJ; van Lettow M; Chimbetete C; Phiri SJ; Egger M; Ballif M; Yiannoutsos CT; Schomaker M; Kassanjee R; Davies MA; Cornell M; Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.; Newlands Clinic, Harare, Zimbabwe.; Wellcome Centre for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine.; SolidarMed, Maseru, Lesotho.; Centre for Infectious Disease Epidemiology and Research, University of Cape Town, Cape Town, South Africa.; Centre for Infectious Diseases Research in Zambia, Lusaka, Zambia.; Lighthouse Trust Clinic, Lilongwe, Malawi.; SolidarMed, Pemba, Mozambique.; SolidarMed, Masvingo, Zimbabwe.; R.M. Fairbanks School of Public Health, Department of Biostatistics, Indiana University, Indianapolis, IN; and.; Dignitas International, Zomba, Malawi.; Department of Statistics, Ludwig-Maximilians-Universität München, München, Germany.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)BACKGROUND: Antiretroviral therapy program mortality maybe underestimated if deceased patients are misclassified as lost. METHODS: We used two-stage inverse probability weighting to account for probability of being: sampled for tracing and found by the tracer. RESULTS: Among 680 children and youth aged <25 years on antiretroviral therapy who were lost and traced in Southern Africa between October 2017 and November 2019, estimated mortality was high at 9.1% (62/680). After adjusting for measured covariates and within-site clustering, mortality remained lower for young adults aged 20-24 years compared with infants aged <2 years [adjusted hazard ratio: 0.40 (95% confidence interval: 0.31 to 0.51)]. CONCLUSIONS: Our study confirms high unreported mortality in children and youth who are lost and the need for tracing to assess vital status among those who are lost to accurately report on program mortality.Item Seasonal variations in tuberculosis diagnosis among HIV-positive individuals in Southern Africa: analysis of cohort studies at antiretroviral treatment programmes.(2018-Jan-11) Ballif M; Zürcher K; Reid SE; Boulle A; Fox MP; Prozesky HW; Chimbetete C; Zwahlen M; Egger M; Fenner L; Newlands Clinic, Harare, Zimbabwe.; Department of Internal Medicine, Health Economics and Epidemiology Research Office, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.; Division of Infection Diseases, University of Alabama at Birmingham, Birmingham, Alabama, USA.; Centre for Infectious Disease Epidemiology and Research (CIDER), School of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa.; Division of Infectious Diseases, Department of Medicine, University of Stellenbosch & Tygerberg Academic Hospital, Cape Town, South Africa.; Departments of Epidemiology and Global Health, Boston University, Boston, USA.; Institute of Social and Preventive Medicine, University of Bern, Bern, BE, Switzerland.; Médecins Sans Frontières, Khayelitsha, South Africa.; Tuberculosis Department Unit, Centre for Infectious Disease Research in Zambia (CIDRZ), Lusaka, Zambia.OBJECTIVES: Seasonal variations in tuberculosis diagnoses have been attributed to seasonal climatic changes and indoor crowding during colder winter months. We investigated trends in pulmonary tuberculosis (PTB) diagnosis at antiretroviral therapy (ART) programmes in Southern Africa. SETTING: Five ART programmes participating in the International Epidemiology Database to Evaluate AIDS in South Africa, Zambia and Zimbabwe. PARTICIPANTS: We analysed data of 331 634 HIV-positive adults (>15 years), who initiated ART between January 2004 and December 2014. PRIMARY OUTCOME MEASURE: We calculated aggregated averages in monthly counts of PTB diagnoses and ART initiations. To account for time trends, we compared deviations of monthly event counts to yearly averages, and calculated correlation coefficients. We used multivariable regressions to assess associations between deviations of monthly ART initiation and PTB diagnosis counts from yearly averages, adjusted for monthly air temperatures and geographical latitude. As controls, we used Kaposi sarcoma and extrapulmonary tuberculosis (EPTB) diagnoses. RESULTS: All programmes showed monthly variations in PTB diagnoses that paralleled fluctuations in ART initiations, with recurrent patterns across 2004-2014. The strongest drops in PTB diagnoses occurred in December, followed by April-May in Zimbabwe and South Africa. This corresponded to holiday seasons, when clinical activities are reduced. We observed little monthly variation in ART initiations and PTB diagnoses in Zambia. Correlation coefficients supported parallel trends in ART initiations and PTB diagnoses (correlation coefficient: 0.28, 95% CI 0.21 to 0.35, P<0.001). Monthly temperatures and latitude did not substantially change regression coefficients between ART initiations and PTB diagnoses. Trends in Kaposi sarcoma and EPTB diagnoses similarly followed changes in ART initiations throughout the year. CONCLUSIONS: Monthly variations in PTB diagnosis at ART programmes in Southern Africa likely occurred regardless of seasonal variations in temperatures or latitude and reflected fluctuations in clinical activities and changes in health-seeking behaviour throughout the year, rather than climatic factors.Item The long-term impact of the COVID-19 pandemic on tuberculosis care and infection control measures in anti-retroviral therapy (ART) clinics in low- and middle-income countries: a multiregional site survey in Asia and Africa.(2025-Mar-24) Ballif M; Banholzer N; Perrig L; Avihingsanon A; Nsonde DM; Obatsa S; Muula G; Komena E; Uemura H; Lelo P; Otaalo B; Huwa J; Gouéssé P; Kumarasamy N; Brazier E; Michael D; Rafael I; Ramdé R; Somia IKA; Yotebieng M; Diero L; Euvrard J; Ezechi O; Fenner L; City University of New York, Institute for Implementation Science in Population Health, New York, NY, USA.; Pediatric Hospital of Kalembelembe, Kinshasa, Democratic Republic of the Congo.; Centre for Reproduction and Population Health Studies, Nigerian Institute of Medical Research, Lagos, Nigeria.; HIV-NAT / Thai Red Cross AIDS Research Centre and Center of Excellence in Tuberculosis, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.; Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.; Infectious Diseases Institute, Makerere University College of Health Sciences, Kampala, Uganda.; Centre for Microbiology and Research, Kenya Medical Research Institute, Kisumu, Kenya.; School of Public Health, University of Cape Town, Cape Town, South Africa.; Division of General Internal Medicine, Department of Medicine, Albert Einstein College of Medicine, Bronx, NY, USA.; CHU Sourô Sanou, Bobo-Dioulasso, Burkina Faso.; PAC-CI program, Abidjan, Côte d'Ivoire.; Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland lukas.fenner@unibe.ch.; Department of Infectious Diseases, Bern University Hospital, University of Bern, Bern, Switzerland.; CART Clinical Research Site, Voluntary Health Services, Chennai, India.; SolidarMed, Chiure, Mozambique.; Lighthouse Trust, Lilongwe, Malawi.; Kisesa Observation Cohort study, National Institute for Medical Reseach, Mwanza, Tanzania.; Faculty of Medicine, Udayana University, Ngoerah Hospital, Bali, Indonesia.; Centre de Traitement Ambulatoire, Brazzaville, Republic of Congo.; Department of Medicine, Moi University, AMPATH Program / Moi Teaching and Referral Hospital, Eldoret, Kenya.; CePReF, Abidjan, Côte d'Ivoire.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; AIDS Clinical Center, National Center for Global Health and Medicine, Tokyo, Japan.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)BACKGROUND: The COVID-19 pandemic challenged healthcare systems, particularly in settings with high infectious disease burden. We examined the postpandemic long-term impacts of COVID-19 on tuberculosis (TB) services at anti-retroviral therapy (ART) clinics in lower-income countries. METHODS: Using standardised online questionnaires, we conducted a cross-sectional site survey among ART clinics providing TB services in Africa and Asia from July to September 2023 (site-level information and number of TB diagnoses and tests). RESULTS: Of 45 participating ART clinics, 32 (71%) were in Africa and 13 (29%) in Asia. During the COVID-19 pandemic (2020-2022), 43 (96%) clinics reported implementing social distancing or separation measures, 39 (87%) personal protections for staff members and 32 (71%) protections for patients. Infection control measures were in place in 45% of the clinics before the pandemic (until 2019), 23% introduced measures during the pandemic and 15% maintained them after the pandemic (after 2022). Service provision was affected during the pandemic in 33 (73%) clinics, including TB services in 22 (49%) clinics. TB service restrictions were addressed by introducing changes in directly observed therapy provision in 8 (18%) clinics, multimonth TB drug dispensing in 23 (51%), telehealth services in 25 (56%) and differentiated service delivery in 19 (42%). These changes were sustained after the pandemic at 4 (9%), 11 (24%), 17 (38%) and 12 (27%) clinics, respectively. Compared with 2018-2019, the number of TB diagnoses decreased sharply in 2020-2021 and improved after the pandemic. CONCLUSIONS: COVID-19 affected TB care services in ART clinics in Africa and Asia. This was paralleled by a reduction in TB diagnoses, which partly resumed after the pandemic. Infection control measures and alternative modes of service delivery were adopted during the pandemic and only partially maintained. Efforts should be made to sustain the lessons learnt during the COVID-19 pandemic, particularly approaches that reduce the risk of transmission of infectious diseases, including TB, in ART clinics.Item The Tuberculosis Sentinel Research Network (TB-SRN) of the International epidemiology Databases to Evaluate AIDS (IeDEA): protocol for a prospective cohort study in Africa, Southeast Asia and Latin America.(2024-Jan-09) Enane LA; Duda SN; Chanyachukul T; Bolton-Moore C; Navuluri N; Messou E; Mbonze N; McDade LR; Figueiredo MC; Ross J; Evans D; Diero L; Akpata R; Zotova N; Freeman A; Pierre MF; Rupasinghe D; Ballif M; Byakwaga H; de Castro N; Tabala M; Sterling TR; Sohn AH; Fenner L; Wools-Kaloustian K; Poda A; Yotebieng M; Huebner R; Marcy O; Vanderbilt Institute of Clinical and Translational Research, Vanderbilt University Medical Center, Nashville, Tennessee, USA.; Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.; Department of Biomedical Informatics, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.; Division of General Internal Medicine, Department of Medicine, Albert Einstein College of Medicine, Bronx, New York, USA.; Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.; Duke Global Health Institute, Duke University, Durham, North Carolina, USA.; Division of Infectious Diseases, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA.; Indiana University Center for Global Health Equity, Indianapolis, Indiana, USA.; Mbarara University of Science and Technology Faculty of Medicine, Mbarara, Uganda.; Department of Infectious Diseases, Bern University Hospital and University of Bern, Bern, Switzerland.; Center for Infectious Disease Research in Zambia (CIDRZ), Lusaka, Zambia.; Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.; The Haitian Group for the Study of Kaposi's Sarcoma and Opportunistic Infections (GHESKIO), Port-au-Prince, Haiti.; The Kirby Institute, UNSW, Sydney, New South Wales, Australia.; Health Economics and Epidemiology Research Office, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.; Centre Hospitalier Universitaire Sourô Sanou, Bobo Dioulasso, Burkina Faso.; TREAT Asia/amfAR - The Foundation for AIDS Research, Bangkok, Thailand.; Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA.; Kinshasa School of Public Health, University of Kinshasa, Kinshasa, Democratic Republic of the Congo.; The Ryan White Center for Pediatric Infectious Diseases and Global Health, Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana, USA lenane@iu.edu.; Vanderbilt Tuberculosis Center, Division of Infectious Diseases, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.; Centre de Prise en Charge de Recherche et de Formation (Aconda-CePReF), Abidjan, Côte d'Ivoire.; Université de Bordeaux, Bordeaux, France.; Department of Medicine, Moi University College of Health Sciences, Eldoret, Kenya.INTRODUCTION: Tuberculosis (TB) is a leading infectious cause of death globally. It is the most common opportunistic infection in people living with HIV, and the most common cause of their morbidity and mortality. Following TB treatment, surviving individuals may be at risk for post-TB lung disease. The TB Sentinel Research Network (TB-SRN) provides a platform for coordinated observational TB research within the International epidemiology Databases to Evaluate AIDS (IeDEA) consortium. METHODS AND ANALYSIS: This prospective, observational cohort study will assess treatment and post-treatment outcomes of pulmonary TB (microbiologically confirmed or clinically diagnosed) among 2600 people aged ≥15 years, with and without HIV coinfection, consecutively enrolled at 16 sites in 11 countries, across 6 of IeDEA's global regions. Data regarding clinical and sociodemographic factors, mental health, health-related quality of life, pulmonary function, and laboratory and radiographic findings will be collected using standardised questionnaires and data collection tools, beginning from the initiation of TB treatment and through 12 months after the end of treatment. Data will be aggregated for proposed analyses. ETHICS AND DISSEMINATION: Ethics approval was obtained at all implementing study sites, including the Vanderbilt University Medical Center Human Research Protections Programme. Participants will provide informed consent; for minors, this includes both adolescent assent and the consent of their parent or primary caregiver. Protections for vulnerable groups are included, in alignment with local standards and considerations at sites. Procedures for requesting use and analysis of TB-SRN data are publicly available. Findings from TB-SRN analyses will be shared with national TB programmes to inform TB programming and policy, and disseminated at regional and global conferences and other venues.Item Tracing People Living With Human Immunodeficiency Virus Who Are Lost to Follow-up at Antiretroviral Therapy Programs in Southern Africa: A Sampling-Based Cohort Study in 6 Countries.(2022-Jan-29) Ballif M; Christ B; Anderegg N; Chammartin F; Muhairwe J; Jefferys L; Hector J; van Dijk J; Vinikoor MJ; van Lettow M; Chimbetete C; Phiri SJ; Onoya D; Fox MP; Egger M; Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.; Newlands Clinic, Harare, Zimbabwe.; Lighthouse Trust Clinic, Lilongwe, Malawi.; Centre for Infectious Diseases Research in Zambia, Lusaka, Zambia.; SolidarMed, Maseru, Lesotho.; Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom.; SolidarMed, Pemba, Mozambique.; SolidarMed, Masvingo, Zimbabwe.; Health Economics and Epidemiology Research Office, Department of Internal Medicine, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, South Africa.; Dignitas International, Zomba, Malawi.; Department of Epidemiology and Global Health, Boston University School of Public Health, Boston, Massachusetts, USA.; Centre for Infectious Disease Research and Epidemiology, University of Cape Town, Cape Town, South Africa.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)BACKGROUND: Attrition threatens the success of antiretroviral therapy (ART). In this cohort study, we examined outcomes of people living with human immunodeficiency virus (PLHIV) who were lost to follow-up (LTFU) during 2014-2017 at ART programs in Southern Africa. METHODS: We confirmed LTFU (missed appointment for ≥60 or ≥90 days, according to local guidelines) by checking medical records and used a standardized protocol to trace a weighted random sample of PLHIV who were LTFU in 8 ART programs in Lesotho, Malawi, Mozambique, South Africa, Zambia, and Zimbabwe, 2017-2019. We ascertained vital status and identified predictors of mortality using logistic regression, adjusted for sex, age, time on ART, time since LTFU, travel time, and urban or rural setting. RESULTS: Among 3256 PLHIV, 385 (12%) were wrongly categorized as LTFU and 577 (17%) had missing contact details. We traced 2294 PLHIV (71%) by phone calls, home visits, or both: 768 (34% of 2294) were alive and in care, including 385 (17%) silent transfers to another clinic; 528 (23%) were alive without care or unknown care; 252 (11%) had died. Overall, the status of 1323 (41% of 3256) PLHIV remained unknown. Mortality was higher in men than women, higher in children than in young people or adults, and higher in PLHIV who had been on ART <1 year or LTFU ≥1 year and those living farther from the clinic or in rural areas. Results were heterogeneous across sites. CONCLUSIONS: Our study highlights the urgent need for better medical record systems at HIV clinics and rapid tracing of PLHIV who are LTFU.