Incidence of switching to second-line antiretroviral therapy and associated factors in children with HIV

an international cohort collaboration

The Collaborative Initiative for Paediatric HIV Education and Research (CIPHER) Global Cohort Collaboration

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Background: Estimates of incidence of switching to second-line antiretroviral therapy (ART) among children with HIV are necessary to inform the need for paediatric second-line formulations. We aimed to quantify the cumulative incidence of switching to second-line ART among children in an international cohort collaboration. Methods: In this international cohort collaboration study, we pooled individual patient-level data for children younger than 18 years who initiated ART (two or more nucleoside reverse-transcriptase inhibitors [NRTI] plus a non-NRTI [NNRTI] or boosted protease inhibitor) between 1993 and 2015 from 12 observational cohort networks in the Collaborative Initiative for Paediatric HIV Education and Research (CIPHER) Global Cohort Collaboration. Patients who were reported to be horizontally infected with HIV and those who were enrolled in trials of treatment monitoring, switching, or interruption strategies were excluded. Switch to second-line ART was defined as change of one or more NRTI plus either change in drug class (NNRTI to protease inhibitor or vice versa) or protease inhibitor change, change from single to dual protease inhibitor, or addition of a new drug class. We used cumulative incidence curves to assess time to switching, and multivariable proportional hazards models to explore patient-level and cohort-level factors associated with switching, with death and loss to follow-up as competing risks. Findings: At the data cutoff of Sept 16, 2015, 182 747 children with HIV were included in the CIPHER dataset, of whom 93 351 were eligible, with 83 984 (90·0%) from sub-Saharan Africa. At ART initiation, the median patient age was 3·9 years (IQR 1·6–6·9) and 82 885 (88·8%) patients initiated NNRTI-based and 10 466 (11·2%) initiated protease inhibitor-based regimens. Median duration of follow-up after ART initiation was 26 months (IQR 9–52). 3883 (4·2%) patients switched to second-line ART after a median of 35 months (IQR 20–57) of ART. The cumulative incidence of switching at 3 years was 3·1% (95% CI 3·0–3·2), but this estimate varied widely depending on the cohort monitoring strategy, from 6·8% (6·5–7·2) in settings with routine monitoring of CD4 (CD4% or CD4 count) and viral load to 0·8% (0·6–1·0) in settings with clinical only monitoring. In multivariable analyses, patient-level factors associated with an increased likelihood of switching were male sex, older age at ART initiation, and initial NNRTI-based regimen (p<0·0001). Cohort-level factors that increased the likelihood of switching were higher-income country (p=0·0017) and routine or targeted monitoring of CD4 and viral load (p<0·0001), which was associated with a 166% increase in likelihood of switching compared with CD4 only monitoring (subdistributional hazard ratio 2·66, 95% CI 2·22–3·19). Interpretation: Our global paediatric analysis found wide variations in the incidence of switching to second-line ART across monitoring strategies. These findings suggest the scale-up of viral load monitoring would probably increase demand for paediatric second-line ART formulations. Funding: International AIDS Society-CIPHER.

Original languageEnglish (US)
Pages (from-to)e105-e115
JournalThe Lancet HIV
Volume6
Issue number2
DOIs
StatePublished - Feb 1 2019

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HIV
Incidence
Protease Inhibitors
Pediatrics
Reverse Transcriptase Inhibitors
Therapeutics
Viral Load
Nucleosides
Education
Research
Africa South of the Sahara
CD4 Lymphocyte Count
Proportional Hazards Models
Pharmaceutical Preparations
Cohort Studies

ASJC Scopus subject areas

  • Epidemiology
  • Immunology
  • Infectious Diseases
  • Virology

Cite this

The Collaborative Initiative for Paediatric HIV Education and Research (CIPHER) Global Cohort Collaboration (2019). Incidence of switching to second-line antiretroviral therapy and associated factors in children with HIV: an international cohort collaboration. The Lancet HIV, 6(2), e105-e115. https://doi.org/10.1016/S2352-3018(18)30319-9
The Collaborative Initiative for Paediatric HIV Education and Research (CIPHER) Global Cohort Collaboration. / Incidence of switching to second-line antiretroviral therapy and associated factors in children with HIV : an international cohort collaboration. In: The Lancet HIV. 2019 ; Vol. 6, No. 2. pp. e105-e115.
@article{57314b2914534958a34cc821e36ff7fa,
title = "Incidence of switching to second-line antiretroviral therapy and associated factors in children with HIV: an international cohort collaboration",
abstract = "Background: Estimates of incidence of switching to second-line antiretroviral therapy (ART) among children with HIV are necessary to inform the need for paediatric second-line formulations. We aimed to quantify the cumulative incidence of switching to second-line ART among children in an international cohort collaboration. Methods: In this international cohort collaboration study, we pooled individual patient-level data for children younger than 18 years who initiated ART (two or more nucleoside reverse-transcriptase inhibitors [NRTI] plus a non-NRTI [NNRTI] or boosted protease inhibitor) between 1993 and 2015 from 12 observational cohort networks in the Collaborative Initiative for Paediatric HIV Education and Research (CIPHER) Global Cohort Collaboration. Patients who were reported to be horizontally infected with HIV and those who were enrolled in trials of treatment monitoring, switching, or interruption strategies were excluded. Switch to second-line ART was defined as change of one or more NRTI plus either change in drug class (NNRTI to protease inhibitor or vice versa) or protease inhibitor change, change from single to dual protease inhibitor, or addition of a new drug class. We used cumulative incidence curves to assess time to switching, and multivariable proportional hazards models to explore patient-level and cohort-level factors associated with switching, with death and loss to follow-up as competing risks. Findings: At the data cutoff of Sept 16, 2015, 182 747 children with HIV were included in the CIPHER dataset, of whom 93 351 were eligible, with 83 984 (90·0{\%}) from sub-Saharan Africa. At ART initiation, the median patient age was 3·9 years (IQR 1·6–6·9) and 82 885 (88·8{\%}) patients initiated NNRTI-based and 10 466 (11·2{\%}) initiated protease inhibitor-based regimens. Median duration of follow-up after ART initiation was 26 months (IQR 9–52). 3883 (4·2{\%}) patients switched to second-line ART after a median of 35 months (IQR 20–57) of ART. The cumulative incidence of switching at 3 years was 3·1{\%} (95{\%} CI 3·0–3·2), but this estimate varied widely depending on the cohort monitoring strategy, from 6·8{\%} (6·5–7·2) in settings with routine monitoring of CD4 (CD4{\%} or CD4 count) and viral load to 0·8{\%} (0·6–1·0) in settings with clinical only monitoring. In multivariable analyses, patient-level factors associated with an increased likelihood of switching were male sex, older age at ART initiation, and initial NNRTI-based regimen (p<0·0001). Cohort-level factors that increased the likelihood of switching were higher-income country (p=0·0017) and routine or targeted monitoring of CD4 and viral load (p<0·0001), which was associated with a 166{\%} increase in likelihood of switching compared with CD4 only monitoring (subdistributional hazard ratio 2·66, 95{\%} CI 2·22–3·19). Interpretation: Our global paediatric analysis found wide variations in the incidence of switching to second-line ART across monitoring strategies. These findings suggest the scale-up of viral load monitoring would probably increase demand for paediatric second-line ART formulations. Funding: International AIDS Society-CIPHER.",
author = "{The Collaborative Initiative for Paediatric HIV Education and Research (CIPHER) Global Cohort Collaboration} and Collins, {Intira J.} and Kara Wools-Kaloustian and Ruth Goodall and Colette Smith and Abrams, {Elaine J.} and Jihane Ben-Farhat and Suna Balkan and Davies, {Mary Ann} and Andrew Edmonds and Val{\'e}riane Leroy and Harriet Nuwagaba-Biribonwoha and Kunjal Patel and Paul, {Mary E.} and Jorge Pinto and {Rojo Conejo}, Pablo and Annette Sohn and {Van Dyke}, Russell and Rachel Vreeman and Nicky Maxwell and Venessa Timmerman and Charlotte Duff and Ali Judd and George Seage and Paige Williams and Gibb, {Diana M.} and Bekker, {Linda Gail} and Lynne Mofenson and Marissa Vicari and Shaffiq Essajee and Mohapi, {Edith Q.} and Kazembe, {Peter N.} and Makhosazana Hlatshwayo and Mwita Lumumba and Adeodata Kekitiinwa-Rukyalekere and Sebastian Wanless and Matshaba, {Mogomotsi S.} and Tessa Goetghebuer and Claire Thorne and Josiane Warszawski and Luisa Galli and Sybil Geelen and Carlo Giaquinto and Magdalena Marczynska and Laura Marques and Filipa Prata and Luminita Ene and Liubov Okhonskaia and Antoni Noguera-Julian and Lars Naver and Ellen Chadwick",
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The Collaborative Initiative for Paediatric HIV Education and Research (CIPHER) Global Cohort Collaboration 2019, 'Incidence of switching to second-line antiretroviral therapy and associated factors in children with HIV: an international cohort collaboration', The Lancet HIV, vol. 6, no. 2, pp. e105-e115. https://doi.org/10.1016/S2352-3018(18)30319-9

Incidence of switching to second-line antiretroviral therapy and associated factors in children with HIV : an international cohort collaboration. / The Collaborative Initiative for Paediatric HIV Education and Research (CIPHER) Global Cohort Collaboration.

In: The Lancet HIV, Vol. 6, No. 2, 01.02.2019, p. e105-e115.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Incidence of switching to second-line antiretroviral therapy and associated factors in children with HIV

T2 - an international cohort collaboration

AU - The Collaborative Initiative for Paediatric HIV Education and Research (CIPHER) Global Cohort Collaboration

AU - Collins, Intira J.

AU - Wools-Kaloustian, Kara

AU - Goodall, Ruth

AU - Smith, Colette

AU - Abrams, Elaine J.

AU - Ben-Farhat, Jihane

AU - Balkan, Suna

AU - Davies, Mary Ann

AU - Edmonds, Andrew

AU - Leroy, Valériane

AU - Nuwagaba-Biribonwoha, Harriet

AU - Patel, Kunjal

AU - Paul, Mary E.

AU - Pinto, Jorge

AU - Rojo Conejo, Pablo

AU - Sohn, Annette

AU - Van Dyke, Russell

AU - Vreeman, Rachel

AU - Maxwell, Nicky

AU - Timmerman, Venessa

AU - Duff, Charlotte

AU - Judd, Ali

AU - Seage, George

AU - Williams, Paige

AU - Gibb, Diana M.

AU - Bekker, Linda Gail

AU - Mofenson, Lynne

AU - Vicari, Marissa

AU - Essajee, Shaffiq

AU - Mohapi, Edith Q.

AU - Kazembe, Peter N.

AU - Hlatshwayo, Makhosazana

AU - Lumumba, Mwita

AU - Kekitiinwa-Rukyalekere, Adeodata

AU - Wanless, Sebastian

AU - Matshaba, Mogomotsi S.

AU - Goetghebuer, Tessa

AU - Thorne, Claire

AU - Warszawski, Josiane

AU - Galli, Luisa

AU - Geelen, Sybil

AU - Giaquinto, Carlo

AU - Marczynska, Magdalena

AU - Marques, Laura

AU - Prata, Filipa

AU - Ene, Luminita

AU - Okhonskaia, Liubov

AU - Noguera-Julian, Antoni

AU - Naver, Lars

AU - Chadwick, Ellen

PY - 2019/2/1

Y1 - 2019/2/1

N2 - Background: Estimates of incidence of switching to second-line antiretroviral therapy (ART) among children with HIV are necessary to inform the need for paediatric second-line formulations. We aimed to quantify the cumulative incidence of switching to second-line ART among children in an international cohort collaboration. Methods: In this international cohort collaboration study, we pooled individual patient-level data for children younger than 18 years who initiated ART (two or more nucleoside reverse-transcriptase inhibitors [NRTI] plus a non-NRTI [NNRTI] or boosted protease inhibitor) between 1993 and 2015 from 12 observational cohort networks in the Collaborative Initiative for Paediatric HIV Education and Research (CIPHER) Global Cohort Collaboration. Patients who were reported to be horizontally infected with HIV and those who were enrolled in trials of treatment monitoring, switching, or interruption strategies were excluded. Switch to second-line ART was defined as change of one or more NRTI plus either change in drug class (NNRTI to protease inhibitor or vice versa) or protease inhibitor change, change from single to dual protease inhibitor, or addition of a new drug class. We used cumulative incidence curves to assess time to switching, and multivariable proportional hazards models to explore patient-level and cohort-level factors associated with switching, with death and loss to follow-up as competing risks. Findings: At the data cutoff of Sept 16, 2015, 182 747 children with HIV were included in the CIPHER dataset, of whom 93 351 were eligible, with 83 984 (90·0%) from sub-Saharan Africa. At ART initiation, the median patient age was 3·9 years (IQR 1·6–6·9) and 82 885 (88·8%) patients initiated NNRTI-based and 10 466 (11·2%) initiated protease inhibitor-based regimens. Median duration of follow-up after ART initiation was 26 months (IQR 9–52). 3883 (4·2%) patients switched to second-line ART after a median of 35 months (IQR 20–57) of ART. The cumulative incidence of switching at 3 years was 3·1% (95% CI 3·0–3·2), but this estimate varied widely depending on the cohort monitoring strategy, from 6·8% (6·5–7·2) in settings with routine monitoring of CD4 (CD4% or CD4 count) and viral load to 0·8% (0·6–1·0) in settings with clinical only monitoring. In multivariable analyses, patient-level factors associated with an increased likelihood of switching were male sex, older age at ART initiation, and initial NNRTI-based regimen (p<0·0001). Cohort-level factors that increased the likelihood of switching were higher-income country (p=0·0017) and routine or targeted monitoring of CD4 and viral load (p<0·0001), which was associated with a 166% increase in likelihood of switching compared with CD4 only monitoring (subdistributional hazard ratio 2·66, 95% CI 2·22–3·19). Interpretation: Our global paediatric analysis found wide variations in the incidence of switching to second-line ART across monitoring strategies. These findings suggest the scale-up of viral load monitoring would probably increase demand for paediatric second-line ART formulations. Funding: International AIDS Society-CIPHER.

AB - Background: Estimates of incidence of switching to second-line antiretroviral therapy (ART) among children with HIV are necessary to inform the need for paediatric second-line formulations. We aimed to quantify the cumulative incidence of switching to second-line ART among children in an international cohort collaboration. Methods: In this international cohort collaboration study, we pooled individual patient-level data for children younger than 18 years who initiated ART (two or more nucleoside reverse-transcriptase inhibitors [NRTI] plus a non-NRTI [NNRTI] or boosted protease inhibitor) between 1993 and 2015 from 12 observational cohort networks in the Collaborative Initiative for Paediatric HIV Education and Research (CIPHER) Global Cohort Collaboration. Patients who were reported to be horizontally infected with HIV and those who were enrolled in trials of treatment monitoring, switching, or interruption strategies were excluded. Switch to second-line ART was defined as change of one or more NRTI plus either change in drug class (NNRTI to protease inhibitor or vice versa) or protease inhibitor change, change from single to dual protease inhibitor, or addition of a new drug class. We used cumulative incidence curves to assess time to switching, and multivariable proportional hazards models to explore patient-level and cohort-level factors associated with switching, with death and loss to follow-up as competing risks. Findings: At the data cutoff of Sept 16, 2015, 182 747 children with HIV were included in the CIPHER dataset, of whom 93 351 were eligible, with 83 984 (90·0%) from sub-Saharan Africa. At ART initiation, the median patient age was 3·9 years (IQR 1·6–6·9) and 82 885 (88·8%) patients initiated NNRTI-based and 10 466 (11·2%) initiated protease inhibitor-based regimens. Median duration of follow-up after ART initiation was 26 months (IQR 9–52). 3883 (4·2%) patients switched to second-line ART after a median of 35 months (IQR 20–57) of ART. The cumulative incidence of switching at 3 years was 3·1% (95% CI 3·0–3·2), but this estimate varied widely depending on the cohort monitoring strategy, from 6·8% (6·5–7·2) in settings with routine monitoring of CD4 (CD4% or CD4 count) and viral load to 0·8% (0·6–1·0) in settings with clinical only monitoring. In multivariable analyses, patient-level factors associated with an increased likelihood of switching were male sex, older age at ART initiation, and initial NNRTI-based regimen (p<0·0001). Cohort-level factors that increased the likelihood of switching were higher-income country (p=0·0017) and routine or targeted monitoring of CD4 and viral load (p<0·0001), which was associated with a 166% increase in likelihood of switching compared with CD4 only monitoring (subdistributional hazard ratio 2·66, 95% CI 2·22–3·19). Interpretation: Our global paediatric analysis found wide variations in the incidence of switching to second-line ART across monitoring strategies. These findings suggest the scale-up of viral load monitoring would probably increase demand for paediatric second-line ART formulations. Funding: International AIDS Society-CIPHER.

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The Collaborative Initiative for Paediatric HIV Education and Research (CIPHER) Global Cohort Collaboration. Incidence of switching to second-line antiretroviral therapy and associated factors in children with HIV: an international cohort collaboration. The Lancet HIV. 2019 Feb 1;6(2):e105-e115. https://doi.org/10.1016/S2352-3018(18)30319-9