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. 2018 Mar 1;15(3):e1002514.
doi: 10.1371/journal.pmed.1002514. eCollection 2018 Mar.

The epidemiology of adolescents living with perinatally acquired HIV: A cross-region global cohort analysis

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 , Jihane Ben-Farhat  3 , Nancy Calles  4 , Kulkanya Chokephaibulkit  5 , Charlotte Duff  6 , Tanoh François Eboua  7 , Adeodata Kekitiinwa-Rukyalekere  8 , Nicola Maxwell  1 , Jorge Pinto  9 , George Seage 3rd  2 , Chloe A Teasdale  10 , Sebastian Wanless  4 , Josiane Warszawski  11 , Kara Wools-Kaloustian  12 , Marcel Yotebieng  13 , Venessa Timmerman  1 , Intira J Collins  6 , Ruth Goodall  6 , Colette Smith  6 , Kunjal Patel  2 , Mary Paul  4 , Diana Gibb  6 , Rachel Vreeman  12 , Elaine J Abrams  10 , Rohan Hazra  14 , Russell Van Dyke  15 , Linda-Gail Bekker  16 , Lynne Mofenson  17 , Marissa Vicari  18 , Shaffiq Essajee  19 , Martina Penazzato  20 , Gabriel Anabwani  21 , Edith Q Mohapi  22 , Peter N Kazembe  23 , Makhosazana Hlatshwayo  24 , Mwita Lumumba  25 , Tessa Goetghebuer  26 , Claire Thorne  27 , Luisa Galli  28 , Annemarie van Rossum  29 , Carlo Giaquinto  30 , Magdalena Marczynska  31 , Laura Marques  32 , Filipa Prata  33 , Luminita Ene  34 , Liubov Okhonskaia  35 , Pablo Rojo  36 , Claudia Fortuny  37 , Lars Naver  38 , Christoph Rudin  39 , Sophie Le Coeur  40   41 , Alla Volokha  42 , Vanessa Rouzier  43 , Regina Succi  44 , Annette Sohn  45 , Azar Kariminia  46 , Andrew Edmonds  47 , Patricia Lelo  48 , Samuel Ayaya  49 , Patricia Ongwen  50 , Laura F Jefferys  51 , Sam Phiri  52 , Mwangelwa Mubiana-Mbewe  53 , Shobna Sawry  54   55 , Lorna Renner  56 , Mariam Sylla  57 , Mark J Abzug  58 , Myron Levin  58 , James Oleske  59 , Miriam Chernoff  2 , Shirley Traite  2 , Murli Purswani  60 , Ellen G Chadwick  61 , Ali Judd  6 , Valériane Leroy  62
Affiliations

The epidemiology of adolescents living with perinatally acquired HIV: A cross-region global cohort analysis

Collaborative Initiative for Paediatric HIV Education and Research (CIPHER) Global Cohort Collaboration et al. PLoS Med. .

Abstract

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.

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Conflict of interest statement

I have read the journal's policy and the authors of this manuscript have the following competing interests: AS's institution receives research and travel funding from ViiV Healthcare. CT has participated in an advisory board for ViiV Healthcare and received research grants from the European Commission, UK Medical Research Council, Public Health England, PENTA Foundation, Abbvie, and ViiV. CT is on the Advisory Board of the Antiretroviral Pregnancy Registry, the Board of the PENTA Foundation, and the UK Infectious Diseases in Pregnancy Screening Advisory Group. MV's work at CIPHER is funded through Unrestricted Educational grants received from ViiV Healthcare and Janssen to the International AIDS Society. CS has received personal payment for preparation of educational materials for Gilead Sciences and ViiV Healthcare. JW's institution has received academic grants from the INSERM-ANRS for cohorts of JW's responsibility involved in the study. SW receives a fee from Baylor International Pediatric AIDS Initiative for consultancy services related to research. MJA receives funding from NIH to perform research in the IMPAACT network. LGB is guest editor for the PLOS Medicine HIV Collection.

Figures

Fig 1
Fig 1. Flow diagram of inclusion of adolescents living with perinatally acquired HIV (N = 38,187).
CIPHER, Collaborative Initiative for Paediatric HIV Education and Research.
Fig 2
Fig 2. Comparison by geographic region of characteristics at first visit, ART start, age 10 years, and last visit of adolescents living with perinatally acquired HIV.
ART, antiretroviral therapy; IQR, interquartile range; S&SE Asia, South and Southeast Asia; WHO, World Health Organization.
Fig 3
Fig 3. Comparison by CIG of characteristics at first visit, ART start, age 10 years, and last visit of adolescents living with perinatally acquired HIV.
ART, antiretroviral therapy; CIG, country income group; IQR, interquartile range; WHO, World Health Organization.
See this image and copyright information in PMC

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