Growth and CD4 patterns of adolescents living with perinatally acquired HIV worldwide, a CIPHER cohort collaboration analysis
Authors:   The Collaborative Initiative for Paediatric HIV Education and Research (CIPHER) Global Cohort Collaboration, Jesson Julie , Crichton Siobhan , Quartagno Matteo , Yotebieng Marcel , Abrams Elaine J. , Chokephaibulkit Kulkanya , Le Coeur Sophie , Aké‐Assi Marie‐Hélène , Patel Kunjal , Pinto Jorge , Paul Mary , Vreeman Rachel , Davies Mary‐Ann , Ben‐Farhat Jihane , Van Dyke Russell , Judd Ali , Mofenson Lynne , Vicari Marissa , Seage George , Bekker Linda‐Gail , Essajee Shaffiq , Gibb Diana , Penazzato Martina , Collins Intira Jeannie , Wools‐Kaloustian Kara , Slogrove Amy , Powis Kate , Williams Paige , Matshaba Mogomotsi , Thahane Lineo , Nyasulu Phoebe , Lukhele Bhekumusa , Mwita Lumumba , Kekitiinwa‐Rukyalekere Adeodata , Wanless Sebastian , Goetghebuer Tessa , Thorne Claire , Warszawski Josiane , Galli Luisa , van Rossum Annemarie M.C , Giaquinto Carlo , Marczynska Magdalena , Marques Laura , Prata Filipa , Ene Luminita , Okhonskaya Lyuba , Navarro Marisa , Frick Antoinette , Naver Lars , Kahlert Christian , Volokha Alla , Chappell Elizabeth , Pape Jean William , Rouzier Vanessa , Marcelin Adias , Succi Regina , Sohn Annette H. , Kariminia Azar , Edmonds Andrew , Lelo Patricia , Lyamuya Rita , Ogalo Edith Apondi , Odhiambo Francesca Akoth , Haas Andreas D. , Bolton Carolyn , Muhairwe Josephine , Tweya Hannock , Sylla Mariam , D'Almeida Marceline , Renner Lorna , Abzug Mark J. , Oleske James , Purswani Murli , Teasdale Chloe , Nuwagaba‐Biribonwoha Harriet , Goodall Ruth , Leroy Valériane 
Published: March 2022

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/mm3. Across adolescence, higher HAZ was observed in females and among those in high‐income countries. APH with stunting at age 10 and those with late ART initiation (after age 5) had the largest HAZ gains during adolescence, but these gains were insufficient to catch‐up with non‐stunted, early ART‐treated adolescents. From age 10 to 16 years, mean CD4 counts declined from 768 to 607 cells/mm3. This decline was observed across all regions, in males and females.

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.