Browsing by Author "Bekker LG"

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    Growth and CD4 patterns of adolescents living with perinatally acquired HIV worldwide, a CIPHER cohort collaboration analysis.
    (2022-Mar) Jesson J; Crichton S; Quartagno M; Yotebieng M; Abrams EJ; Chokephaibulkit K; Le Coeur S; Aké-Assi MH; Patel K; Pinto J; Paul M; Vreeman R; Davies MA; Ben-Farhat J; Van Dyke R; Judd A; Mofenson L; Vicari M; Seage G; Bekker LG; Essajee S; Gibb D; Penazzato M; Collins IJ; Wools-Kaloustian K; Slogrove A; Powis K; Williams P; Matshaba M; Thahane L; Nyasulu P; Lukhele B; Mwita L; Kekitiinwa-Rukyalekere A; Wanless S; Goetghebuer T; Thorne C; Warszawski J; Galli L; van Rossum AMC; Giaquinto C; Marczynska M; Marques L; Prata F; Ene L; Okhonskaya L; Navarro M; Frick A; Naver L; Kahlert C; Volokha A; Chappell E; Pape JW; Rouzier V; Marcelin A; Succi R; Sohn AH; Kariminia A; Edmonds A; Lelo P; Lyamuya R; Ogalo EA; Odhiambo FA; Haas AD; Bolton C; Muhairwe J; Tweya H; Sylla M; D'Almeida M; Renner L; Abzug MJ; Oleske J; Purswani M; Teasdale C; Nuwagaba-Biribonwoha H; Goodall R; Leroy V; Medical University of Warsaw, Hospital of Infectious Diseases in Warsaw, Warsaw, Poland.; TREAT Asia/amfAR, Bangkok, Thailand.; Baylor College of Medicine Children's Foundation, Mwanza, Tanzania.; Hospital St Pierre, Brussels, Belgium.; Inserm U1018, Centre de recherche en Epidémiologie et Santé des Populations, Paris, France.; Division of General Internal Medicine, Department of Medicine, Albert Einstein College of Medicine, Bronx, New York, USA.; Moi Teaching and Referral Hospital, Eldoret, Kenya.; Hospital General Universitario "Gregorio Marañón", Madrid, Spain.; HIV Department, World Health Organization, Geneva, Switzerland.; Elizabeth Glaser Pediatric AIDS Foundation, Washington, DC, USA.; Padova University/PENTA Foundation, Padua, Italy.; School of Public Health and Family Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.; Baylor College of Medicine Children's Foundation, Maseru, Lesotho.; Baylor College of Medicine Children's Foundation, Lilongwe, Botswana.; Baylor College of Medicine Children's Foundation, Kampala, Uganda.; Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.; Department of Global Health, Icahn School of Medicine at Mount Sinai, New York, USA.; International AIDS Society, Geneva, Switzerland.; Epicentre, Médecins Sans Frontières, Paris, France.; Baylor College of Medicine Children's Foundation, Lilongwe, Malawi.; Hospital de Santa Maria, Lisboa, Portugal.; Institut National d'Etude Demographique (INED), Mortality, Health and Epidemiology Unit, Paris, France.; Desmond Tutu HIV Centre, University of Cape Town, Cape Town, South Africa.; Centro Hospitalar do Porto, Porto, Portugal.; Indiana University School of Medicine, Indianapolis, Indiana, USA.; Korle Bu Teaching Hospital, Accra, Ghana.; UCL Great Ormond Street Institute of Child Health, University College London, London, UK.; Morogoro Regional Hospital, Morogoro, Tanzania.; Center for Microbiology Research, Kenya Medical Research Institute, Nairobi, Kenya.; Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.; Department of Health Sciences, University of Florence, Florence, Italy.; Baylor International Pediatric AIDS Initiative, Texas Children's Hospital-USA, Houston, Texas, USA.; Victor Babes Hospital, Bucharest, Romania.; MRC Clinical Trials Unit, University College London, London, UK.; Children's Hospital of Eastern Switzerland, Saint Gallen, Switzerland.; University Hospital Yopougon, Abidjan, Côte d'Ivoire.; Erasmus MC University Medical Center Rotterdam-Sophia Children's Hospital, Rotterdam, The Netherlands.; Department of Paediatrics & Child Health, Faculty of Medicine & Health Sciences, Stellenbosch University, Worcester, South Africa.; Lighthouse Trust Clinic, Lilongwe, Malawi.; Kirby Institute, University of New South Wales, Sydney, New South Wales, Australia.; Rutgers - New Jersey Medical School, Newark, New Jersey, USA.; Institut de Recherche pour le Developpement (IRD), UMI-174/PHPT, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand.; Siriraj Institute of Clinical Research, Faculty of Medicine Siriraj Hospital, Mahidol University, Salaya, Thailand.; Baylor College of Medicine Children's Foundation, Mbabane, eSwatini.; SolidarMed, Lesotho, Zimbabwe.; CHU Gabriel Toure, Bamako, Mali.; Centre National Hospitalier Universitaire Hubert K. Maga, Cotonou, Benin.; Bronx-Lebanon Hospital Center, Bronx, New York, USA.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; Karolinska University Hospital and Karolinska Institutet, Stockholm, Sweden.; Tulane University Health Sciences Center, New Orleans, Louisiana, USA.; University of Colorado School of Medicine and Children's Hospital Colorado, Aurora, Colorado, USA.; GHESKIO Center, Port-au-Prince, Haiti.; Republican Hospital of Infectious Diseases, St Petersburg, Russian Federation.; Department of Pediatrics, School of Medicine, Federal University of Minas Gerais, Belo Horizonte, Brazil.; UNICEF, New York, USA.; CERPOP, Inserm, Université Paul Sabatier Toulouse 3, Toulouse, France.; Universidade Federal de Sao Paulo, Sao Paulo, Brazil.; Infection Disease Unit, Meyer Children's University Hospital, Florence, Italy.; Harvard T. H. Chan School of Public Health, Boston, Massachusetts, USA.; Pediatric Hospital Kalembe Lembe, Lingwala, Demogratic Republic of Congo.; Shupyk National Medical Academy of Postgraduate Education, Kiev, Ukraine.; ICAP at Columbia University, Mailman School of Public Health, Columbia University, New York, USA.; Hospital Universitari Vall d' Hebron, Vall d' Hebron Research Institute, Universitat Autònoma de Barcelona, Barcelona, Spain.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
    INTRODUCTION: Adolescents living with HIV are subject to multiple co-morbidities, including growth retardation and immunodeficiency. We describe growth and CD4 evolution during adolescence using data from the Collaborative Initiative for Paediatric HIV Education and Research (CIPHER) global project. METHODS: Data were collected between 1994 and 2015 from 11 CIPHER networks worldwide. Adolescents with perinatally acquired HIV infection (APH) who initiated antiretroviral therapy (ART) before age 10 years, with at least one height or CD4 count measurement while aged 10-17 years, were included. Growth was measured using height-for-age Z-scores (HAZ, stunting if <-2 SD, WHO growth charts). Linear mixed-effects models were used to study the evolution of each outcome between ages 10 and 17. For growth, sex-specific models with fractional polynomials were used to model non-linear relationships for age at ART initiation, HAZ at age 10 and time, defined as current age from 10 to 17 years of age. RESULTS: A total of 20,939 and 19,557 APH were included for the growth and CD4 analyses, respectively. Half were females, two-thirds lived in East and Southern Africa, and median age at ART initiation ranged from <3 years in North America and Europe to >7 years in sub-Saharan African regions. At age 10, stunting ranged from 6% in North America and Europe to 39% in the Asia-Pacific; 19% overall had CD4 counts <500 cells/mm CONCLUSIONS: Growth patterns during adolescence differed substantially by sex and region, while CD4 patterns were similar, with an observed CD4 decline that needs further investigation. Early diagnosis and timely initiation of treatment in early childhood to prevent growth retardation and immunodeficiency are critical to improving APH growth and CD4 outcomes by the time they reach adulthood.
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    Hybrid versus vaccine immunity of mRNA-1273 among people living with HIV in East and Southern Africa: a prospective cohort analysis from the multicentre CoVPN 3008 (Ubuntu) study.
    (2025-Feb) Garrett N; Tapley A; Hudson A; Dadabhai S; Zhang B; Mgodi NM; Andriesen J; Takalani A; Fisher LH; Kee JJ; Magaret CA; Villaran M; Hural J; Andersen-Nissen E; Ferarri G; Miner MD; Le Roux B; Wilkinson E; Lessells R; de Oliveira T; Odhiambo J; Shah P; Polakowski L; Yacovone M; Samandari T; Chirenje Z; Elyanu PJ; Makhema J; Kamuti E; Nuwagaba-Biribonwoha H; Badal-Faesen S; Brumskine W; Coetzer S; Dawson R; Delany-Moretlwe S; Diacon AH; Fry S; Gill KM; Ebrahim Hoosain ZA; Hosseinipour MC; Inambao M; Innes C; Innes S; Kalonji D; Kasaro M; Kassim P; Kayange N; Kilembe W; Laher F; Malahleha M; Maluleke VL; Mboya G; McHarry K; Mitha E; Mngadi K; Mda P; Moloantoa T; Mutuluuza CK; Naicker N; Naicker V; Nana A; Nanvubya A; Nchabeleng M; Otieno W; Potgieter EL; Potloane D; Punt Z; Said J; Singh Y; Tayob MS; Vahed Y; Wabwire DO; McElrath MJ; Kublin JG; Bekker LG; Gilbert PB; Corey L; Gray GE; Huang Y; Kotze P; ICAP at Columbia University, Eswatini Prevention Center, Mbabane, Eswatini.; Nelson Mandela Academic Clinical Research Unit Clinical Research Site, Mthatha, South Africa.; Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington, Seattle, USA.; University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, USA.; South African Medical Research Council, Isipingo Clinical Research Site, KwaZulu-Natal, South Africa.; Soweto - Kliptown Clinical Research Site, Soweto, South Africa.; Synergy Biomed Research Institute, East London, South Africa.; Qhakaza Mbokodo Research Clinic, Ladysmith, South Africa.; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, USA.; COVID-19 Prevention Network, Seattle, USA.; Wits RHI University of the Witwatersrand, Johannesburg, South Africa.; TASK Eden, Western Cape, South Africa.; Synexus Stanza Clinical Research Centre Clinical Research Site, Pretoria, South Africa.; TASK Central, Cape Town, South Africa.; Department of Global Health, University of Washington, Seattle, USA.; KwaZulu-Natal Research Innovation & Sequencing Platform, School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, South Africa.; Discipline of Public Health Medicine, School of Nursing and Public Health, University of KwaZulu-Natal, Durban, South Africa.; Moi University Clinical Research Centre, Eldoret, Kenya.; Centre for the AIDS Programme of Research in South Africa, University of KwaZulu-Natal, Durban, South Africa.; Baylor College of Medicine Children's Foundation-Uganda, Kampala, Uganda.; Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, USA.; PHOENIX Pharma (Pty) Ltd, Port Elizabeth, South Africa.; Kisumu Clinical Research Site, Kisumu, Kenya.; South African Medical Research Council, Pretoria, South Africa.; Perinatal HIV Research Unit, Faculty of Health Sciences, University of the Witwatersrand, South Africa.; FAMCRU Family Clinical Research Unit, Cape Town, South Africa.; Desmond Tutu HIV Centre, University of Cape Town, Cape Town, South Africa.; Joint Clinical Research Centre, Lubowa, Uganda.; MU-JHU Research Collaboration Clinical Research Site, Kampala, Uganda.; Johns Hopkins Research Project, Blantyre, Malawi.; Center for HIV/AIDS Vaccine Immunology, Duke University School of Medicine, Durham, NC, USA.; National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, USA.; Duke University Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA.; The Aurum Institute, Rustenburg Clinical Research Site, Rustenburg, South Africa.; Synexus Helderberg, Cape Town, South Africa.; The Aurum Institute, Klerksdorp Clinical Research Site, Klerksdorp, South Africa.; MERC Kempton, Kempton, South Africa.; Malawi Clinical Research Site, Lilongwe, Malawi.; MERC Welkom, Welkom, South Africa.; Cape Town HVTN Immunology Laboratory, Hutchinson Centre Research Institute of South Africa, Cape Town, South Africa.; Hutchinson Centre Research Institute of South Africa, Chris Hani Baragwanath Academic Hospital, Soweto, South Africa.; CFHRZ - Ndola Clinical Research Site, Ndola, Zambia.; Department of Medicine, University of Cape Town, Cape Town, South Africa.; University of Cape Town Lung Institute Clinical Research Site, Cape Town, South Africa.; Josha Research Clinical Research Site, Bloemfontein, South Africa.; MERC Middelburg, Middelburg, South Africa.; Centre for Epidemic Response & Innovation, Stellenbosch, South Africa.; Clinical Trials Research Centre, University of Zimbabwe, Harare, Zimbabwe.; Kombewa Clinical Research Site, Kisumu, Kenya.; Maseno University School of Medicine, Kenya.; UNC Global Projects/Kamwala District Health Centre, Lusaka, Zambia.; UVRI-IAVI HIV Vaccine Program Ltd. Clinical Research Site, Entebbe, Uganda.; Botswana Harvard AIDS Institute, Gaborone, Botswana.; PHRU Matlosana Clinical Research Site, Klerksdorp, South Africa.; MeCRU Clinical Research Site, Pretoria, South Africa.; Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, USA.; Tembisa Clinic 4, Gauteng, South Africa.; Blantyre Clinical Research Site, Blantyre, Malawi.; CFHRZ Clinical Research Site, Lusaka, Zambia.; Newtown Clinical Research, Johannesburg, South Africa.; Clinical HIV Research Unit/Helen Joseph Clinical Research Site, Johannesburg, South Africa.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; Tongaat Clinical Research Site, KwaZulu-Natal, South Africa.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
    BACKGROUND: With limited access to mRNA COVID-19 vaccines in lower income countries, and people living with HIV (PLWH) largely excluded from clinical trials, Part A of the multicentre CoVPN 3008 (Ubuntu) study aimed to assess the safety of mRNA-1273, the relative effectiveness of hybrid versus vaccine immunity, and SARS-CoV-2 viral persistence among PLWH in East and Southern Africa during the omicron outbreak. METHODS: Previously unvaccinated adults with HIV and/or other comorbidities associated with severe COVID-19 received either one (hybrid immunity) or two (vaccine immunity) 100-mcg doses of ancestral strain mRNA-1273 in the first month, depending on baseline evidence of prior SARS-CoV-2 infection. In a prospective cohort study design, we used covariate-adjusted Cox regression and counterfactual cumulative incidence methods to determine the hazard ratio and relative risk of COVID-19 and severe COVID-19 with hybrid versus vaccine immunity within six months. The ongoing Ubuntu study is registered on ClinicalTrials.gov (NCT05168813) and this work was conducted from December 2021 to March 2023. FINDINGS: Between December 2021 and September 2022, 14,237 participants enrolled, and 14,002 (83% PLWH, 69% SARS-CoV-2 seropositive) were included in the analyses. Vaccinations were safe and well tolerated. Common adverse events were pain or tenderness at the injection site (26.7%), headache (20.4%), and malaise (20.3%). Severe adverse events were rare (0.8% of participants after the first and 1.1% after the second vaccination), and none were life-threatening or fatal. Among PLWH, the median CD4 count was 635 cells/μl and 18.5% had HIV viraemia. The six-month cumulative incidences in the hybrid immunity and vaccine immunity groups were 2.02% (95% confidence interval [CI] 1.61-2.44) and 3.40% (95% CI 2.30-4.49) for COVID-19, and 0.048% (95% CI 0.00-0.10) and 0.32% (95% CI 0.59-0.63) for severe COVID-19. Among all PLWH the hybrid immunity group had a 42% lower hazard rate of COVID-19 (hazard ratio [HR] 0.58; 95% CI 0.44-0.77; p < 0.001) and a 73% lower hazard rate of severe COVID-19 (HR 0.27; 95% CI 0.07-1.04; p = 0.056) than the vaccine immunity group, but this effect was not seen among PLWH with CD4 counts <350 cells/μl or HIV viraemia. Twenty PLWH had persistent SARS-CoV-2 virus at least 50 days. INTERPRETATION: Hybrid immunity was associated with superior protection from COVID-19 compared to vaccine immunity with the ancestral mRNA-1273 vaccine. Persistent infections among immunocompromised PLWH may provide reservoirs for emerging variants. FUNDING: National Institute of Allergy and Infectious Diseases.
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    Reimagining HIV prevention with artificial intelligence.
    (2025-Jun-11) Ratevosian J; Reid M; Ni Z; Mendonca R; Eakle R; Johnson C; Sikazwe I; Ndirangu M; Baptiste S; Bekker LG; Desmond Tutu Health Foundation, Cape Town, South Africa.; International Treatment Preparedness Coalition (ITPC), Johannesberg, South Africa.; Washington, DC, USA.; Duke University, Washington 20001, DC, USA. Electronic address: jirair.ratevosian@duke.edu.; Centre for Infectious Disease Research in Zambia (CIDRZ), Lusaka, Zambia.; Yale University, New Haven, CT, USA.; World Health Organization, Geneva, Switzerland.; Audere Africa, Seattle, WA, USA.; Amref Health Africa, Nairobi, Kenya.; University of California, San Francisco (UCSF), San Francisco, CA, USA.
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    The epidemiology of adolescents living with perinatally acquired HIV: A cross-region global cohort analysis.
    (2018-Mar) Slogrove AL; Schomaker M; Davies MA; Williams P; Balkan S; Ben-Farhat J; Calles N; Chokephaibulkit K; Duff C; Eboua TF; Kekitiinwa-Rukyalekere A; Maxwell N; Pinto J; Seage G; Teasdale CA; Wanless S; Warszawski J; Wools-Kaloustian K; Yotebieng M; Timmerman V; Collins IJ; Goodall R; Smith C; Patel K; Paul M; Gibb D; Vreeman R; Abrams EJ; Hazra R; Van Dyke R; Bekker LG; Mofenson L; Vicari M; Essajee S; Penazzato M; Anabwani G; Q Mohapi E; N Kazembe P; Hlatshwayo M; Lumumba M; Goetghebuer T; Thorne C; Galli L; van Rossum A; Giaquinto C; Marczynska M; Marques L; Prata F; Ene L; Okhonskaia L; Rojo P; Fortuny C; Naver L; Rudin C; Le Coeur S; Volokha A; Rouzier V; Succi R; Sohn A; Kariminia A; Edmonds A; Lelo P; Ayaya S; Ongwen P; Jefferys LF; Phiri S; Mubiana-Mbewe M; Sawry S; Renner L; Sylla M; Abzug MJ; Levin M; Oleske J; Chernoff M; Traite S; Purswani M; Chadwick EG; Judd A; Leroy V; Baylor International Pediatric AIDS Initiative, Mbabane, Swaziland.; Medical University of Warsaw, Hospital of Infectious Diseases in Warsaw, Warsaw, Poland.; Institut National d'Etudes Démograhiques (Ined), F-75020 Paris, France.; TREAT Asia/amfAR, Bangkok, Thailand.; Baylor International Pediatric AIDS Initiative, Lilongwe, Malawi.; CHU Gabriel Touré, Bamako, Mali.; Bronx-Lebanon Hospital Center (Icahn School of Medicine at Mount Sinai), Bronx, New York, United States of America.; Harvard T. H. Chan School of Public Health, Boston, Massachusetts, United States of America.; Baylor International Pediatric AIDS Initiative, Maseru, Lesotho.; Harriet Shezi Children's Clinic, Chris Hani Baragwanath Hospital, Johannesburg, South Africa.; Baylor International Pediatric AIDS Initiative, Texas Children's Hospital-USA, Houston, Texas, United States of America.; Feinberg School of Medicine, Northwestern University, Evanston, Illinois, United States of America.; SolidarMed Lesotho, Mozambique and Zimbabwe, Lucerne, Switzerland.; Hospital Doce de Octubre, Madrid, Spain.; Wits Reproductive Health and HIV Institute, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.; MRC Clinical Trials Unit at University College London, London, United Kingdom.; Inserm (French Institute of Health and Medical Research), UMR 1027 Université Toulouse 3, Toulouse, France.; Yopougon University Hospital, University Félix Houphouët-Boigny, Abidjan, Côte d'Ivoire.; Indiana University School of Medicine, Indianapolis, Indiana, United States of America.; Baylor International Pediatric AIDS Initiative, Gaborone, Botswana.; Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand.; International AIDS Society, Geneva, Switzerland.; Epicentre, Médecins Sans Frontières, Paris, France.; Universidade Federal de São Paulo, São Paulo, Brazil.; Centro Hospitalar do Porto, Porto, Portugal.; Desmond Tutu HIV Centre, University of Cape Town, Cape Town, South Africa.; Pediatric Hospital Kalembe Lembe, Lingwala, Kinshasa, Democratic Republic of Congo.; ICAP at Columbia University Mailman School of Public Health, New York, New York, United States of America.; Karolinska University Hospital, Stockholm, Sweden.; Gillings School of Global Public Health, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.; Hospital St Pierre Cohort, Bruxelles, Belgium.; Center for Infectious Disease Research in Zambia, Lusaka, Zambia.; Institute of Child Health, University College London, London, United Kingdom.; Department of Health Sciences, University of Florence, Florence, Italy.; Victor Babes Hospital, Bucharest, Romania.; University of Colorado School of Medicine and Children's Hospital Colorado, Aurora, Colorado, United States of America.; Kirby Institute, UNSW, Sydney, Australia.; UNICEF, New York, New York, United States of America.; Institut de Recherche pour le Développement (IRD) 174/PHPT, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand.; Rutgers New Jersey Medical School, Newark, New Jersey, United States of America.; Lighthouse Trust Clinic, Lilongwe, Malawi.; World Health Organization, Geneva, Switzerland.; College of Public Health, Ohio State University, Columbus, Ohio, United States of America.; Hospital Sant Joan de Déu, Universitat de Barcelona, Barcelona, Spain.; Center for Infectious Diseases Epidemiology and Research, University of Cape Town, Cape Town, South Africa.; University Children's Hospital, Basel, Switzerland.; Family AIDS Care and Education Services, Kenya Medical Research Institute, Kisumu, Kenya.; Inserm (French Institute of Health and Medical Research), CESP UMR Villejuif, France.; Tulane University, New Orleans, Louisiana, United States of America.; National Institute of Child Health and Human Development (NICHD), US National Institutes of Health, Rockville, Maryland, United States of America.; Elizabeth Glaser Pediatric AIDS Foundation, Washington, DC, United States of America.; GHESKIO Center, Port-au-Prince, Haiti.; Academic Model Providing Access to Healthcare (AMPATH), Eldoret, Kenya.; School of Medicine, Federal University of Minas Gerais, Belo Horizonte, Brazil.; Republican Hospital of Infectious Diseases, St Petersburg, Russian Federation.; Baylor International Pediatric AIDS Initiative, Mbeya, Tanzania.; University of Ghana School of Medicine and Dentistry, Accra, Ghana.; Erasmus MC University Medical Center Rotterdam-Sophia Children's Hospital, Rotterdam, the Netherlands.; Hospital de Santa Maria/CHLN, Lisbon, Portugal.; Shupyk National Medical Academy of Postgraduate Education, Kiev, Ukraine.; Baylor International Pediatric AIDS Initiative, Kampala, Uganda.; PENTA Foundation, Padova, Italy.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
    BACKGROUND: Globally, the population of adolescents living with perinatally acquired HIV (APHs) continues to expand. In this study, we pooled data from observational pediatric HIV cohorts and cohort networks, allowing comparisons of adolescents with perinatally acquired HIV in "real-life" settings across multiple regions. We describe the geographic and temporal characteristics and mortality outcomes of APHs across multiple regions, including South America and the Caribbean, North America, Europe, sub-Saharan Africa, and South and Southeast Asia. METHODS AND FINDINGS: Through the Collaborative Initiative for Paediatric HIV Education and Research (CIPHER), individual retrospective longitudinal data from 12 cohort networks were pooled. All children infected with HIV who entered care before age 10 years, were not known to have horizontally acquired HIV, and were followed up beyond age 10 years were included in this analysis conducted from May 2016 to January 2017. Our primary analysis describes patient and treatment characteristics of APHs at key time points, including first HIV-associated clinic visit, antiretroviral therapy (ART) start, age 10 years, and last visit, and compares these characteristics by geographic region, country income group (CIG), and birth period. Our secondary analysis describes mortality, transfer out, and lost to follow-up (LTFU) as outcomes at age 15 years, using competing risk analysis. Among the 38,187 APHs included, 51% were female, 79% were from sub-Saharan Africa and 65% lived in low-income countries. APHs from 51 countries were included (Europe: 14 countries and 3,054 APHs; North America: 1 country and 1,032 APHs; South America and the Caribbean: 4 countries and 903 APHs; South and Southeast Asia: 7 countries and 2,902 APHs; sub-Saharan Africa, 25 countries and 30,296 APHs). Observation started as early as 1982 in Europe and 1996 in sub-Saharan Africa, and continued until at least 2014 in all regions. The median (interquartile range [IQR]) duration of adolescent follow-up was 3.1 (1.5-5.2) years for the total cohort and 6.4 (3.6-8.0) years in Europe, 3.7 (2.0-5.4) years in North America, 2.5 (1.2-4.4) years in South and Southeast Asia, 5.0 (2.7-7.5) years in South America and the Caribbean, and 2.1 (0.9-3.8) years in sub-Saharan Africa. Median (IQR) age at first visit differed substantially by region, ranging from 0.7 (0.3-2.1) years in North America to 7.1 (5.3-8.6) years in sub-Saharan Africa. The median age at ART start varied from 0.9 (0.4-2.6) years in North America to 7.9 (6.0-9.3) years in sub-Saharan Africa. The cumulative incidence estimates (95% confidence interval [CI]) at age 15 years for mortality, transfers out, and LTFU for all APHs were 2.6% (2.4%-2.8%), 15.6% (15.1%-16.0%), and 11.3% (10.9%-11.8%), respectively. Mortality was lowest in Europe (0.8% [0.5%-1.1%]) and highest in South America and the Caribbean (4.4% [3.1%-6.1%]). However, LTFU was lowest in South America and the Caribbean (4.8% [3.4%-6.7%]) and highest in sub-Saharan Africa (13.2% [12.6%-13.7%]). Study limitations include the high LTFU rate in sub-Saharan Africa, which could have affected the comparison of mortality across regions; inclusion of data only for APHs receiving ART from some countries; and unavailability of data from high-burden countries such as Nigeria. CONCLUSION: To our knowledge, our study represents the largest multiregional epidemiological analysis of APHs. Despite probable under-ascertained mortality, mortality in APHs remains substantially higher in sub-Saharan Africa, South and Southeast Asia, and South America and the Caribbean than in Europe. Collaborations such as CIPHER enable us to monitor current global temporal trends in outcomes over time to inform appropriate policy responses.