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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) globalproject. 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 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 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 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. Keywords: adolescent; CD4; cohort studies; growth; HIV; perinatally acquired Additional information may be found under the Supporting Information tab of this article., 1 | INTRODUCTION In 2019, an estimated 1.7 million adolescents aged 10-19 years were living with HIV worldwide, with 90% of them in sub-Saharan Africa, and 8% in Asia and [...]

: Introduction: Limited data describe outcomes on second‐line antiretroviral therapy (ART) among children globally. Our objective was to contribute data on outcomes among children living with HIV after initiation of second‐line ART in the context of routine care within a large global cohort collaboration. Methods: Patient‐level data from 1993 through 2015 from 11 paediatric HIV cohorts were pooled. Characteristics at switch and through two years of follow‐up were summarized for children who switched to second‐line ART after starting a standard first‐line regimen in North America, Latin America, Europe, Asia, Southern Africa (South Africa & Botswana) and the rest of sub‐Saharan Africa (SSA). Cumulative incidences of mortality and loss to follow‐up (LTFU) were estimated using a competing risks framework. Results: Of the 85,389 children on first‐line ART, 3,555 (4%) switched to second‐line after a median of 2.8 years on ART (IQR: 1.6, 4.7); 69% were from Southern Africa or SSA and 86% of second‐line regimens were protease inhibitor‐based. At switch, median age was 8.4 years and 50% had a prior AIDS diagnosis. Median follow‐up after switch to second‐line ranged from 1.8 years in SSA to 5.3 years in North America. Median CD4 counts at switch to second‐line ranged from 235 cells/mm[sup.3] in SSA to 828 cells/mm[sup.3] in North America. Improvements in CD4 counts were observed over two years of follow‐up, particularly in regions with lower CD4 counts at second‐line switch. Improvements in weight‐for‐age z‐scores were not observed during follow‐up. Cumulative incidence of LTFU at two years was Conclusions: Children switched to second‐line ART experience CD4 count increases as well as low to moderate rates of LTFU and mortality within two years after switch. Severe immune deficiency at time of switch in some settings suggests need for improved recognition and management of treatment failure in children., Introduction In 2018, there were an estimated 1.7 million children living with HIV globally and 160,000 new paediatric infections [1]. With the recommendation for immediate antiretroviral therapy (ART) [2], substantial [...]

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., Author(s): The Collaborative Initiative for Paediatric HIV Education and Research (CIPHER) Global Cohort Collaboration, Amy L. Slogrove 1, Michael Schomaker 1, Mary-Ann Davies 1, Paige Williams 2, Suna Balkan 3, [...]

: Introduction: Eighty percent of adolescents living with perinatally and behaviourally acquired HIV live in sub‐Saharan Africa (SSA), a continent with marked economic inequality. As part of our global project describing adolescents living with perinatally acquired HIV (APH), we aimed to assess whether inequality in outcomes exists by country income group (CIG) for APH within SSA. Methods: Through the CIPHER cohort collaboration, individual retrospective data from 7 networks and 25 countries in SSA were included. APH were included if they entered care at age 10 years. World Bank CIG classification for median year of first visit was used. Cumulative incidence of mortality, transfer‐out and loss‐to‐follow‐up was calculated by competing risks analysis. Mortality was compared across CIG by Cox proportional hazards models. Results: A total of 30,296 APH were included; 50.9% were female and 75.7% were resident in low‐income countries (LIC). Median [interquartile range (IQR)] age at antiretroviral therapy (ART) start was 8.1 [6.3; 9.5], 7.8 [6.2; 9.3] and 7.3 [5.2; 8.9] years in LIC, lower‐middle income countries (LMIC) and upper‐middle income countries (UMIC) respectively. Median age at last follow‐up was 12.1 [10.9; 13.8] years, with no difference between CIG. Cumulative incidence (95% CI) for mortality between age 10 and 15 years was lowest in UMIC (1.1% (0.8; 1.4)) compared to LIC (3.5% (3.1; 3.8)) and LMIC (3.9% (2.7; 5.4)). Loss‐to‐follow‐up was highest in UMIC (14.0% (12.9; 15.3)) compared to LIC (13.1% (12.4; 13.8)) and LMIC (8.3% (6.3; 10.6)). Adjusted mortality hazard ratios (95% CI) for APH in LIC and LMIC in reference to UMIC were 2.50 (1.85; 3.37) and 2.96 (1.90; 4.61) respectively, with little difference when restricted only to APH who ever received ART. In adjusted analyses mortality was similar for male and female APH. Conclusions: Results highlight probable inequality in mortality according to CIG in SSA even when ART was received. These findings highlight that without attention towards SDG 10 (to reduce inequality within and among countries), progress towards ensuring healthy lives and promoting wellbeing for all at all ages (SDG 3) will be hampered for APH in LIC and LMIC., Introduction Sub‐Saharan Africa (SSA) is a complex region marked by diversity and inequality. Across the continent gross national income per capita varies almost thirty fold from 160/1000. Sub‐Saharan Africa is [...]

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. [ABSTRACT FROM AUTHOR]