The epidemiology of adolescents living with perinatally acquired HIV: A cross-region global cohort analysis
Creators: name: The Collaborative Initiative For Paediatric HIV Education And Research (CIPHER) Global Cohort Collaboration
name: Slogrove, Amy L.
name: Schomaker, Michael
name: Davies, Mary-Ann
name: Williams, Paige
name: Balkan, Suna
name: Ben-Farhat, Jihane
name: Calles, Nancy
name: Chokephaibulkit, Kulkanya
name: Duff, Charlotte
name: Eboua, Tanoh Francois
name: Kekitiinwa-Rukyalekere, Adeodata
name: Maxwell, Nicola
name: Pinto, Jorge
name: Seage III, George R.
name: Teasdale, Chloe A.
name: Wanless, Sebastian
name: Warszawski, Josiane
name: Wools-Kaloustian, Kara
name: Yotebieng, Marcel
name: Timmerman, Venessa
name: Collins, Intira J.
name: Goodall, Ruth
name: Smith, Colette
name: Patel, Kunjal
name: Paul, Mary E.
name: Gibb, Diana
name: Vreeman, Rachel
name: Abrams, Elaine J.
name: Hazra, Rohan
name: Van Dyke, Russell
name: Bekker, Linda-Gail
name: Mofenson, Lynne
name: Vicari, Marissa
name: Essajee, Shaffiq
name: Penazzato, Martina
name: Anabwani, Gabriel
name: Mohapi, Edith Q.
name: Kazembe, Peter N.
name: Hlatshwayo, Makhosazana
name: Lumumba, Mwita
name: Goetghebuer, Tessa
name: Thorne, Claire
name: Galli, Luisa
name: Van Rossum, Annemarie
name: Giaquinto, Carlo
name: Marczynska, Magdalena
name: Marques, Laura
name: Prata, Filipa
name: Ene, Luminita
name: Okhonskaia, Liubov
name: Rojo, Pablo
name: Fortuny, Claudia
name: Naver, Lars
name: Rudin, Christoph
name: Le Coeur, Sophie
name: Volokha, Alla
name: Rouzier, Vanessa
name: Succi, Regina
name: Sohn, Annette
name: Kariminia, Azar
name: Edmonds, Andrew
name: Lelo, Patricia
name: Ayaya, Samuel
name: Ongwen, Patricia
name: Jefferys, Laura F.
name: Phiri, Sam
name: Mubiana-Mbewe, Mwangelwa
name: Sawry, Shobna
name: Renner, Lorna
name: Sylla, Mariam
name: Abzug, Mark J.
name: Levin, Myron
name: Oleske, James
name: Chernoff, Miriam
name: Traite, Shirley
name: Purswani, Murli
name: Chadwick, Ellen G.
name: Judd, Ali
name: Leroy, Valeriane
Publisher: name: Columbia University
Year: 2018
Subjects: Epidemiology
Teenagers
Cohort analysis

description: 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.