Abstract
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.
Original language | English (US) |
---|---|
Article number | e25477 |
Journal | Journal of the International AIDS Society |
Volume | 23 |
Issue number | 4 |
DOIs | |
State | Published - Apr 1 2020 |
Keywords
- antiretroviral therapy
- children
- mortality
- outcomes
- perinatal HIV
- second-line
ASJC Scopus subject areas
- Public Health, Environmental and Occupational Health
- Infectious Diseases
Access to Document
Other files and links
Fingerprint
Dive into the research topics of 'Outcomes of second-line antiretroviral therapy among children living with HIV: a global cohort analysis'. Together they form a unique fingerprint.Cite this
- APA
- Author
- BIBTEX
- Harvard
- Standard
- RIS
- Vancouver
}
Outcomes of second-line antiretroviral therapy among children living with HIV : a global cohort analysis. / The Collaborative Initiative for Paediatric HIV Education and Research (CIPHER) Global Cohort Collaboration.
In: Journal of the International AIDS Society, Vol. 23, No. 4, e25477, 01.04.2020.Research output: Contribution to journal › Article › peer-review
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 - Chadwick, Ellen
N1 - Funding Information: The authors thank all participating networks, clinics, clinic personnel and patients who contributed data and made the Collaborative Initiative for Paediatric HIV Education and Research (CIPHER) Global Cohort Collaboration Second‐Line Project possible. We also thank the CIPHER Executive Committee, the CIPHER Steering Committee, the Project Oversight Group, and Samantha Hodgetts for her administrative support. The full list of acknowledgments is available in the Supplement. The study was sponsored by the International AIDS Society‐CIPHER. Funding Information: This work was supported by the International AIDS Society – Collaborative Initiative for Paediatric HIV Education & Research (IAS‐CIPHER, http://www.iasociety.org/CIPHER ) which is made possible through funding from CIPHER Founding Sponsor ViiV Healthcare ( https://www.viivhealthcare.com ) and Janssen ( http://www.janssen.com ). Funding Information: This work was supported by the International AIDS Society ? Collaborative Initiative for Paediatric HIV Education & Research (IAS-CIPHER, http://www.iasociety.org/CIPHER) which is made possible through funding from CIPHER Founding Sponsor ViiV Healthcare (https://www.viivhealthcare.com) and Janssen (http://www.janssen.com). Individual networks contributing to the CIPHER Cohort Collaboration have received the following financial support: IeDEA CCASAnet receives funding from the United States (US) National Institutes of Health (NIH) (grant number U01AI069923); IeDEA Asia Pacific receives funding from the US NIH (grant number U01AI069907); IeDEA Central Africa receives funding from the US NIH (grant number U01AI096299); IeDEA East Africa receives funding from the US NIH (grant number U01A1069911); IeDEA Southern Africa receives funding from the US NIH (grant number U01AI069924); IeDEA West Africa receives funding from the US NIH (grant number U01AI069919); IMPAACT 219C and P1074 are supported by the US NIH (grant numbers UM1AI068632, UM1AI068616, UM1AI106716, and U01AI41110; contract N01-3-3345 and HHSN267200800001C); PHACS receives funding from the US NIH (grant numbers U01 HD052102 and U01 HD052104); The Optimal Models (ICAP at Columbia University) project was supported by the President?s Emergency Plan for AIDS Relief (PEPFAR) through the Centers for Disease Control and Prevention (cooperative agreement numbers: 5U62PS223540 and 5U2GPS001537); EPPICC receives funding from EuroCoord (grant number: no260694), the PENTA Foundation, and was partly funded by the Medical Research Council (https://www.mrc.ac.uk) (programme number MC_UU_12023/26). Individual cohorts contributing to EPPICC receive the following support: The ATHENA database is maintained by Stichting HIV Monitoring and supported by a grant from the Dutch Ministry of Health, Welfare and Sport through the Centre for Infectious Disease Control of the National Institute for Public Health and the Environment. CoRISPE-cat receives financial support from the Instituto de Salud Carlos III through the Red Tem?tica de Investigaci?n Cooperativa en Sida. CoRISPE-s and Madrid Cohort is partially funded by the Fundaci?n para la Investigaci?n y Prevenci?n de SIDA en Espa?a (FIPSE) (grant numbers FIPSE 3608229/09, FIPSE 240800/09, FIPSE 361910/10), Red Tem?tica de Investigaci?n en SIDA (RED RIS) supported by Instituto de Salud Carlos III (ISCIII) (grant numbers RD12/0017/0035 and RD12/0017/0037), project as part of the Plan R+D+I and co-financed by ISCIII- Subdirecci?n General de Evaluaci?n and Fondo Europeo de Desarrollo Regional (FEDER), Mutua Madrile?a 2012/0077, Gilead Fellowship 2013/0071, FIS PI15/00694, CoRISpe (grant numbers RED RIS RD06/0006/0035 yRD06/0006/0021). The Swiss HIV Cohort Study is supported by the Swiss National Science Foundation (grant number: 148522), and by the SHCS Research Foundation. Ukraine Paediatric HV Cohort is supported by the PENTA Foundation. CHIPS is funded by the NHS (London Specialised Commissioning Group) and has received additional support from Bristol-Myers Squibb, Boehringer Ingelheim, GlaxoSmithKline, Roche, Abbott and Gilead Sciences. The MRC Clinical Trials Unit at UCL is supported by the Medical Research Council (programme number MC_UU_12023/26). No funding bodies had any role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. This work is solely the responsibility of the authors and does not necessarily represent the official views of any of the institutions mentioned above. The authors thank all participating networks, clinics, clinic personnel and patients who contributed data and made the Collaborative Initiative for Paediatric HIV Education and Research (CIPHER) Global Cohort Collaboration Second-Line Project possible. We also thank the CIPHER Executive Committee, the CIPHER Steering Committee, the Project Oversight Group, and Samantha Hodgetts for her administrative support. The full list of acknowledgments is available in the Supplement. The study was sponsored by the International AIDS Society-CIPHER. This work was supported by the International AIDS Society ? Collaborative Initiative for Paediatric HIV Education & Research (IAS-CIPHER, http://www.iasociety.org/CIPHER) which is made possible through funding from CIPHER Founding Sponsor ViiV Healthcare (https://www.viivhealthcare.com) and Janssen (http://www.janssen.com). Individual networks contributing to the CIPHER Cohort Collaboration have received the following financial support: IeDEA CCASAnet receives funding from the United States (US) National Institutes of Health (NIH) (grant number U01AI069923); IeDEA Asia Pacific receives funding from the US NIH (grant number U01AI069907); IeDEA Central Africa receives funding from the US NIH (grant number U01AI096299); IeDEA East Africa receives funding from the US NIH (grant number U01A1069911); IeDEA Southern Africa receives funding from the US NIH (grant number U01AI069924); IeDEA West Africa receives funding from the US NIH (grant number U01AI069919); IMPAACT 219C and P1074 are supported by the US NIH (grant numbers UM1AI068632, UM1AI068616, UM1AI106716, and U01AI41110; contract N01-3-3345 and HHSN267200800001C); PHACS receives funding from the US NIH (grant numbers U01 HD052102 and U01 HD052104); The Optimal Models (ICAP at Columbia University) project was supported by the President?s Emergency Plan for AIDS Relief (PEPFAR) through the Centers for Disease Control and Prevention (cooperative agreement numbers: 5U62PS223540 and 5U2GPS001537); EPPICC receives funding from EuroCoord (grant number: no260694), the PENTA Foundation, and was partly funded by the Medical Research Council (https://www.mrc.ac.uk) (programme number MC_UU_12023/26). Individual cohorts contributing to EPPICC receive the following support: The ATHENA database is maintained by Stichting HIV Monitoring and supported by a grant from the Dutch Ministry of Health, Welfare and Sport through the Centre for Infectious Disease Control of the National Institute for Public Health and the Environment. CoRISPE-cat receives financial support from the Instituto de Salud Carlos III through the Red Tem?tica de Investigaci?n Cooperativa en Sida. CoRISPE-s and Madrid Cohort is partially funded by the Fundaci?n para la Investigaci?n y Prevenci?n de SIDA en Espa?a (FIPSE) (grant numbers FIPSE 3608229/09, FIPSE 240800/09, FIPSE 361910/10), Red Tem?tica de Investigaci?n en SIDA (RED RIS) supported by Instituto de Salud Carlos III (ISCIII) (grant numbers RD12/0017/0035 and RD12/0017/0037), project as part of the Plan R+D+I and co-financed by ISCIII- Subdirecci?n General de Evaluaci?n and Fondo Europeo de Desarrollo Regional (FEDER), Mutua Madrile?a 2012/0077, Gilead Fellowship 2013/0071, FIS PI15/00694, CoRISpe (grant numbers RED RIS RD06/0006/0035 yRD06/0006/0021). The Swiss HIV Cohort Study is supported by the Swiss National Science Foundation (grant number: 148522), and by the SHCS Research Foundation. Ukraine Paediatric HV Cohort is supported by the PENTA Foundation. CHIPS is funded by the NHS (London Specialised Commissioning Group) and has received additional support from Bristol-Myers Squibb, Boehringer Ingelheim, GlaxoSmithKline, Roche, Abbott and Gilead Sciences. The MRC Clinical Trials Unit at UCL is supported by the Medical Research Council (programme number MC_UU_12023/26). No funding bodies had any role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. This work is solely the responsibility of the authors and does not necessarily represent the official views of any of the institutions mentioned above. This work was supported by the International AIDS Society ? Collaborative Initiative for Paediatric HIV Education & Research (IAS-CIPHER, http://www.iasociety.org/CIPHER) which is made possible through funding from CIPHER Founding Sponsor ViiV Healthcare (https://www.viivhealthcare.com) and Janssen (http://www.janssen.com). Individual networks contributing to the CIPHER Cohort Collaboration have received the following financial support: IeDEA CCASAnet receives funding from the United States (US) National Institutes of Health (NIH) (grant number U01AI069923); IeDEA Asia Pacific receives funding from the US NIH (grant number U01AI069907); IeDEA Central Africa receives funding from the US NIH (grant number U01AI096299); IeDEA East Africa receives funding from the US NIH (grant number U01A1069911); IeDEA Southern Africa receives funding from the US NIH (grant number U01AI069924); IeDEA West Africa receives funding from the US NIH (grant number U01AI069919); IMPAACT 219C and P1074 are supported by the US NIH (grant numbers UM1AI068632, UM1AI068616, UM1AI106716, and U01AI41110; contract N01-3-3345 and HHSN267200800001C); PHACS receives funding from the US NIH (grant numbers U01 HD052102 and U01 HD052104); The Optimal Models (ICAP at Columbia University) project was supported by the President?s Emergency Plan for AIDS Relief (PEPFAR) through the Centers for Disease Control and Prevention (cooperative agreement numbers: 5U62PS223540 and 5U2GPS001537); EPPICC receives funding from EuroCoord (grant number: no260694), the PENTA Foundation, and was partly funded by the Medical Research Council (https://www.mrc.ac.uk) (programme number MC_UU_12023/26). Individual cohorts contributing to EPPICC receive the following support: The ATHENA database is maintained by Stichting HIV Monitoring and supported by a grant from the Dutch Ministry of Health, Welfare and Sport through the Centre for Infectious Disease Control of the National Institute for Public Health and the Environment. CoRISPE-cat receives financial support from the Instituto de Salud Carlos III through the Red Tem?tica de Investigaci?n Cooperativa en Sida. CoRISPE-s and Madrid Cohort is partially funded by the Fundaci?n para la Investigaci?n y Prevenci?n de SIDA en Espa?a (FIPSE) (grant numbers FIPSE 3608229/09, FIPSE 240800/09, FIPSE 361910/10), Red Tem?tica de Investigaci?n en SIDA (RED RIS) supported by Instituto de Salud Carlos III (ISCIII) (grant numbers RD12/0017/0035 and RD12/0017/0037), project as part of the Plan R+D+I and co-financed by ISCIII- Subdirecci?n General de Evaluaci?n and Fondo Europeo de Desarrollo Regional (FEDER), Mutua Madrile?a 2012/0077, Gilead Fellowship 2013/0071, FIS PI15/00694, CoRISpe (grant numbers RED RIS RD06/0006/0035 yRD06/0006/0021). The Swiss HIV Cohort Study is supported by the Swiss National Science Foundation (grant number: 148522), and by the SHCS Research Foundation. Ukraine Paediatric HV Cohort is supported by the PENTA Foundation. CHIPS is funded by the NHS (London Specialised Commissioning Group) and has received additional support from Bristol-Myers Squibb, Boehringer Ingelheim, GlaxoSmithKline, Roche, Abbott and Gilead Sciences. The MRC Clinical Trials Unit at UCL is supported by the Medical Research Council (programme number MC_UU_12023/26). No funding bodies had any role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. This work is solely the responsibility of the authors and does not necessarily represent the official views of any of the institutions mentioned above. 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
UR - http://www.scopus.com/inward/record.url?scp=85083993919&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85083993919&partnerID=8YFLogxK
U2 - 10.1002/jia2.25477
DO - 10.1002/jia2.25477
M3 - Article
C2 - 32297485
AN - SCOPUS:85083993919
VL - 23
JO - Journal of the International AIDS Society
JF - Journal of the International AIDS Society
SN - 1758-2652
IS - 4
M1 - e25477
ER -