TY - JOUR
T1 - Outcomes of second-line antiretroviral therapy among children living with HIV
T2 - a global cohort analysis
AU - The Collaborative Initiative for Paediatric HIV Education and Research (CIPHER) Global Cohort Collaboration
AU - Patel, Kunjal
AU - Smith, Colette
AU - Collins, Intira Jeannie
AU - Goodall, Ruth
AU - Abrams, Elaine J.
AU - Sohn, Annette H.
AU - Mohamed, Thahira J.
AU - Van Dyke, Russell B.
AU - Rojo, Pablo
AU - Wools-Kaloustian, Kara
AU - Pinto, Jorge
AU - Edmonds, Andrew
AU - Marete, Irene
AU - Paul, Mary
AU - Nuwaqaba-Biribonwoha, Harriet
AU - Leroy, Valériane
AU - Davies, Mary Ann
AU - Vreeman, Rachel
AU - Maxwell, Nicky
AU - Timmerman, Venessa
AU - Duff, Charlotte
AU - Mofenson, Lynne
AU - Bekker, Linda Gail
AU - Vicari, Marissa
AU - Essajee, Shaffiq
AU - Penazzato, Martina
AU - Collins, Intira Jeannie
AU - Wools-Kaloustian, Kara
AU - Goodall, Ruth
AU - Patel, Kunjal
AU - Smith, Colette
AU - Vreeman, Rachel
AU - Slogrove, Amy
AU - Williams, Paige
AU - Crichton, Siobhan
AU - Seage, George
AU - Thahane, Lineo
AU - Kazembe, Peter N.
AU - Lukhele, Bhekumusa
AU - Mwita, Lumumba
AU - Kekitiinwa-Rukyalekere, Adeodata
AU - Wanless, Sebastian
AU - Matshaba, Mogomotsi S.
AU - Collins, Intira Jeannie
AU - Goodall, Ruth
AU - Smith, Colette
AU - Goetghebuer, Tessa
AU - Thorne, Claire
AU - Warszawski, Josiane
AU - Yotebieng, Marcel
N1 - Publisher Copyright:
© 2020 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.
PY - 2020/4/1
Y1 - 2020/4/1
N2 - 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/mm3 in SSA to 828 cells/mm3 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 <5% in all regions except SSA (7.1%) and Southern Africa (7.4%). Risk of mortality was <3% at two years of follow-up in all regions, except Latin America (4.9%) and SSA (5.5%). 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.
AB - 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/mm3 in SSA to 828 cells/mm3 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 <5% in all regions except SSA (7.1%) and Southern Africa (7.4%). Risk of mortality was <3% at two years of follow-up in all regions, except Latin America (4.9%) and SSA (5.5%). 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.
KW - antiretroviral therapy
KW - children
KW - mortality
KW - outcomes
KW - perinatal HIV
KW - second-line
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U2 - 10.1002/jia2.25477
DO - 10.1002/jia2.25477
M3 - Article
C2 - 32297485
AN - SCOPUS:85083993919
SN - 1758-2652
VL - 23
JO - Journal of the International AIDS Society
JF - Journal of the International AIDS Society
IS - 4
M1 - e25477
ER -