Browsing by Author "Yiannoutsos CT"

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Changes in rapid HIV treatment initiation after national "treat all" policy adoption in 6 sub-Saharan African countries: Regression discontinuity analysis.
(2019-Jun) Tymejczyk O; Brazier E; Yiannoutsos CT; Vinikoor M; van Lettow M; Nalugoda F; Urassa M; Sinayobye JD; Rebeiro PF; Wools-Kaloustian K; Davies MA; Zaniewski E; Anderegg N; Liu G; Ford N; Nash D; Richard M. Fairbanks School of Public Health, Indiana University, Indianapolis, Indiana, United States of America.; Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.; Centre for Infectious Disease Epidemiology and Research, School of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa.; Global Hepatitis Programme, HIV/AIDS Department, World Health Organization, Geneva, Switzerland.; Department of Medicine, University of Alabama, Birmingham, Alabama, United States of America.; Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.; Institute for Implementation Science in Population Health, City University of New York, New York, New York, United States of America.; Graduate School of Public Health and Health Policy, City University of New York, New York, New York, United States of America.; Rakai Health Sciences Program, Kalisizo and Entebbe, Uganda.; Rwanda Military Hospital, Kigali, Rwanda.; Dignitas International, Zomba, Malawi.; Mwanza Intervention Trials Unit, National Institute for Medical Research, Mwanza, Tanzania.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; Division of Infectious Diseases, Indiana University School of Medicine, Indianapolis, Indiana, United States of America.; Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
BACKGROUND: Most countries have formally adopted the World Health Organization's 2015 recommendation of universal HIV treatment ("treat all"). However, there are few rigorous assessments of the real-world impact of treat all policies on antiretroviral treatment (ART) uptake across different contexts. METHODS AND FINDINGS: We used longitudinal data for 814,603 patients enrolling in HIV care between 1 January 2004 and 10 July 2018 in 6 countries participating in the global International epidemiology Databases to Evaluate AIDS (IeDEA) consortium: Burundi (N = 11,176), Kenya (N = 179,941), Malawi (N = 84,558), Rwanda (N = 17,396), Uganda (N = 96,286), and Zambia (N = 425,246). Using a quasi-experimental regression discontinuity design, we assessed the change in the proportion initiating ART within 30 days of enrollment in HIV care (rapid ART initiation) after country-level adoption of the treat all policy. A modified Poisson model was used to identify factors associated with failure to initiate ART rapidly under treat all. In each of the 6 countries, over 60% of included patients were female, and median age at enrollment ranged from 32 to 36 years. In all countries studied, national adoption of treat all was associated with large increases in rapid ART initiation. Significant increases in rapid ART initiation immediately after treat all policy adoption were observed in Rwanda, from 44.4% to 78.9% of patients (34.5 percentage points [pp], 95% CI 27.2 to 41.7; p < 0.001), Kenya (25.7 pp, 95% CI 21.8 to 29.5; p < 0.001), Burundi (17.7 pp, 95% CI 6.5 to 28.9; p = 0.002), and Malawi (12.5 pp, 95% CI 7.5 to 17.5; p < 0.001), while no immediate increase was observed in Zambia (0.4 pp, 95% CI -2.9 to 3.8; p = 0.804) and Uganda (-4.2 pp, 95% CI -9.0 to 0.7; p = 0.090). The rate of rapid ART initiation accelerated sharply following treat all policy adoption in Malawi, Uganda, and Zambia; slowed in Kenya; and did not change in Rwanda and Burundi. In post hoc analyses restricted to patients enrolling under treat all, young adults (16-24 years) and men were at increased risk of not rapidly initiating ART (compared to older patients and women, respectively). However, rapid ART initiation following enrollment increased for all groups as more time elapsed since treat all policy adoption. Study limitations include incomplete data on potential ART eligibility criteria, such as clinical status, pregnancy, and enrollment CD4 count, which precluded the assessment of rapid ART initiation specifically among patients known to be eligible for ART before treat all. CONCLUSIONS: Our analysis indicates that adoption of treat all policies had a strong effect on increasing rates of rapid ART initiation, and that these increases followed different trajectories across the 6 countries. Young adults and men still require additional attention to further improve rapid ART initiation.
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.
Global HIV prevention, care and treatment services for children: a cross-sectional survey from the International Epidemiology Databases to Evaluate AIDS (IeDEA) consortium.
(2023-Mar-13) Vreeman RC; Yiannoutsos CT; Yusoff NKN; Wester CW; Edmonds A; Ofner S; Davies MA; Leroy V; Lumbiganon P; de Menezes Succi RC; Twizere C; Brown S; Bolton-Moore C; Takassi OE; Scanlon M; Martin R; Wools-Kaloustian K; Center for Epidemiology and Research in POPulation Health (CERPOP), Inserm, Université de Toulouse, Université Paul Sabatier, Toulouse, France.; Department of Global Health and Health System Design, Icahn School of Medicine at Mount Sinai Arnhold Institute for Global Health, New York, New York, USA rachel.vreeman@mssm.edu.; Department of Epidemiology, The University of North Carolina at Chapel Hill Gillings School of Global Public Health, Chapel Hill, North Carolina, USA.; Centre for Infectious Disease Epidemiology and Research, School of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa.; Department of Biostatistics and Health Data Science, Indiana University Richard M Fairbanks School of Public Health, Indianapolis, Indiana, USA.; Center for Infectious Disease Research in Zambia, Lusaka, Zambia.; Department of Medicine, The University of Alabama at Birmingham Heersink School of Medicine, Birmingham, Alabama, USA.; Vanderbilt Institute for Global Health, Nashville, Tennessee, USA.; Department of Pediatrics, Universidade Federal de São Paulo, Sao Paulo, Brazil.; Département de Pédiatrie, Université de Lomé, Lomé, Togo.; Indiana University Center for Global Health, Indianapolis, Indiana, USA.; Centre National de Référence en Matière de VIH/SIDA, Bujumbura, Burundi.; Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA.; Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.; Department of Paediatrics, Hospital Raja Perempuan Zainab II, Kota Bharu, Malaysia.; Department of Global Health and Health System Design, Icahn School of Medicine at Mount Sinai Arnhold Institute for Global Health, New York, New York, USA.; Department of Pediatrics, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
OBJECTIVES: To assess access children with HIV have to comprehensive HIV care services, to longitudinally evaluate the implementation and scale-up of services, and to use site services and clinical cohort data to explore whether access to these services influences retention in care. METHODS: A cross-sectional standardised survey was completed in 2014-2015 by sites providing paediatric HIV care across regions of the International Epidemiology Databases to Evaluate AIDS (IeDEA) consortium. We developed a comprehensiveness score based on the WHO's nine categories of essential services to categorise sites as 'low' (0-5), 'medium', (6-7) or 'high' (8-9). When available, comprehensiveness scores were compared with scores from a 2009 survey. We used patient-level data with site services to investigate the relationship between the comprehensiveness of services and retention. RESULTS: Survey data from 174 IeDEA sites in 32 countries were analysed. Of the WHO essential services, sites were most likely to offer antiretroviral therapy (ART) provision and counselling (n=173; 99%), co-trimoxazole prophylaxis (168; 97%), prevention of perinatal transmission services (167; 96%), outreach for patient engagement and follow-up (166; 95%), CD4 cell count testing (126; 88%), tuberculosis screening (151; 87%) and select immunisation services (126; 72%). Sites were less likely to offer nutrition/food support (97; 56%), viral load testing (99; 69%) and HIV counselling and testing (69; 40%). 10% of sites rated 'low', 59% 'medium' and 31% 'high' in the comprehensiveness score. The mean comprehensiveness of services score increased significantly from 5.6 in 2009 to 7.3 in 2014 (p<0.001; n=30). Patient-level analysis of lost to follow-up after ART initiation estimated the hazard was highest in sites rated 'low' and lowest in sites rated 'high'. CONCLUSION: This global assessment suggests the potential care impact of scaling-up and sustaining comprehensive paediatric HIV services. Meeting recommendations for comprehensive HIV services should remain a global priority.
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.
Increased prevalence of pregnancy and comparative risk of program attrition among individuals starting HIV treatment in East Africa.
(2018) Holmes CB; Yiannoutsos CT; Elul B; Bukusi E; Ssali J; Kambugu A; Musick BS; Cohen C; Williams C; Diero L; Padian N; Wools-Kaloustian KK; Masaka Regional Hospital, Masaka, Uganda.; National Institute of Allergies and Infectious Diseases, Bethesda, Maryland, United States of America.; Centre for Microbiology Research, Kenya Medical Research Institute, Nairobi, Kenya.; University of California San Francisco, San Francisco, California, United States of America.; University of California, Berkeley, California, United States of America.; Academic Model Providing Access to Health Care (AMPATH), Eldoret, Kenya.; Georgetown University School of Medicine, Washington, DC, United States of America.; Indiana University School of Medicine, Indianapolis, Indiana, United States of America.; Mailman School of Public Health, Columbia University, ICAP at Columbia University, New York, New York, United States of America.; Infectious Diseases Institute, Kampala, Uganda.; Indiana University R.M. Fairbanks School of Public Health, Indianapolis, Indiana, United States of America.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
BACKGROUND: The World Health Organization now recommends initiating all pregnant women on life-long antiretroviral therapy (ART), yet there is limited information about the characteristics and program outcomes of pregnant women already on ART in Africa. Our hypothesis was that pregnant women comprised an increasing proportion of those starting ART, and that sub-groups of these women were at higher risk for program attrition. METHODS AND FINDINGS: We used the International Epidemiology Databases to Evaluate AIDS- East Africa (IeDEA-EA) to conduct a retrospective cohort study including HIV care and treatment programs in Kenya, Uganda, and Tanzania. The cohort consecutively included HIV-infected individuals 13 years or older starting ART 2004-2014. We examined trends over time in the proportion pregnant, their characteristics and program attrition rates compared to others initiating and already receiving ART. 156,474 HIV-infected individuals (67.0% women) started ART. The proportion of individuals starting ART who were pregnant women rose from 5.3% in 2004 to 12.2% in 2014. Mean CD4 cell counts at ART initiation, weighted for annual program size, increased from 2004 to 2014, led by non-pregnant women (annual increase 20 cells/mm3) and men (17 cells/mm3 annually), with lower rates of change in pregnant women (10 cells/mm3 per year) (p<0.0001). There was no significant difference in the cumulative incidence of program attrition at 6 months among pregnant women starting ART and non-pregnant women. However, healthy pregnant women starting ART (WHO stage 1/2) had a higher rate of attrition rate (9.6%), compared with healthy non-pregnant women (6.5%); in contrast among women with WHO stage 3/4 disease, pregnant women had lower attrition (8.4%) than non-pregnant women (14.4%). Among women who initiated ART when healthy and remained in care for six months, subsequent six-month attrition was slightly higher among pregnant women at ART start (3.5%) compared to those who were not pregnant (2.4%), (absolute difference 1.1%, 95% CI 0.7%-1.5%). CONCLUSIONS: Pregnant women comprise an increasing proportion of those initiating ART in Africa, and pregnant women starting ART while healthy are at higher risk for program attrition than non-pregnant women. As ART programs further expand access to healthier pregnant women, further studies are needed to better understand the drivers of loss among this high risk group of women to optimize retention.
Universal definition of loss to follow-up in HIV treatment programs: a statistical analysis of 111 facilities in Africa, Asia, and Latin America.
(2011-Oct) Chi BH; Yiannoutsos CT; Westfall AO; Newman JE; Zhou J; Cesar C; Brinkhof MW; Mwango A; Balestre E; Carriquiry G; Sirisanthana T; Mukumbi H; Martin JN; Grimsrud A; Bacon M; Thiebaut R; University of Alabama at Birmingham, Birmingham, Alabama, United States of America. bchi@cidrz.org; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
BACKGROUND: Although patient attrition is recognized as a threat to the long-term success of antiretroviral therapy programs worldwide, there is no universal definition for classifying patients as lost to follow-up (LTFU). We analyzed data from health facilities across Africa, Asia, and Latin America to empirically determine a standard LTFU definition. METHODS AND FINDINGS: At a set "status classification" date, patients were categorized as either "active" or "LTFU" according to different intervals from time of last clinic encounter. For each threshold, we looked forward 365 d to assess the performance and accuracy of this initial classification. The best-performing definition for LTFU had the lowest proportion of patients misclassified as active or LTFU. Observational data from 111 health facilities-representing 180,718 patients from 19 countries-were included in this study. In the primary analysis, for which data from all facilities were pooled, an interval of 180 d (95% confidence interval [CI]: 173-181 d) since last patient encounter resulted in the fewest misclassifications (7.7%, 95% CI: 7.6%-7.8%). A secondary analysis that gave equal weight to cohorts and to regions generated a similar result (175 d); however, an alternate approach that used inverse weighting for cohorts based on variance and equal weighting for regions produced a slightly lower summary measure (150 d). When examined at the facility level, the best-performing definition varied from 58 to 383 d (mean=150 d), but when a standard definition of 180 d was applied to each facility, only slight increases in misclassification (mean=1.2%, 95% CI: 1.0%-1.5%) were observed. Using this definition, the proportion of patients classified as LTFU by facility ranged from 3.1% to 45.1% (mean=19.9%, 95% CI: 19.1%-21.7%). CONCLUSIONS: Based on this evaluation, we recommend the adoption of ≥180 d since the last clinic visit as a standard LTFU definition. Such standardization is an important step to understanding the reasons that underlie patient attrition and establishing more reliable and comparable program evaluation worldwide. Please see later in the article for the Editors' Summary.