@article{fdi:010078291,
  title = {{I}ncidence of switching to second-line antiretroviral therapy and associated factors in children with {HIV} : an international cohort collaboration [plus {S}upplementary appendix]},
  author = {{T}he {C}ollaborative {I}nitiative for {P}aediatric {HIV} {E}ducation and {R}esearch ({CIPHER}) {G}lobal {C}ohort {C}ollaboration and {C}ollins, {I}.{J}. and {W}ools-{K}aloustian, {K}.  and {G}oodall, {R}. and {S}mith, {C}. and {A}brams, {E}.{J}. and {B}en-{F}arhat, {J}. and {B}alkan, {S}. and {D}avies, {M}.{A}. and {E}dmonds, {A}. and {L}eroy, {V}. and {N}uwagaba-{B}iribonwoha, {H}. and {P}atel, {K}. and {P}aul, {M}.{E}. and {P}into, {J}. and {C}onejo, {P}.{R}. and {S}ohn, {A}. and {V}an {D}yke, {R}. and {V}reeman, {R}. and {M}axwell, {N}. and {T}immerman, {V}. and {D}uff, {C}. and {J}udd, {A}. and {S}eage, {G}. and {W}illiams, {P}. and {G}ibb, {D}.{M}. and {B}ekker, {L}.{G}. and {M}ofenson, {L}. and {V}icari, {M}. and {E}ssajee, {S}. and {M}ohapi, {E}.{Q}. and {K}azembe, {P}.{N}. and {H}latshwayo, {M}. and {L}umumba, {M}. and {K}ekitiinwa-{R}ukyalekere, {A}. and {W}anless, {S}. and {M}atshaba, {M}.{S}. and {G}oetghebuer, {T}. and {T}horne, {C}. and {W}arszawski, {J}. and {G}alli, {L}. and {G}eelen, {S}. and {G}iaquinto, {C}. and {M}arczynska, {M}. and {M}arques, {L}. and {P}rata, {F}. and {E}ne, {L}. and {O}khonskaia, {L}. and {N}oguera-{J}ulian, {A}. and {N}aver, {L}. and {R}udin, {C}. and {J}ourdain, {G}onzague and et al.},
  editor = {},
  language = {{ENG}},
  abstract = {{B}ackground : {E}stimates 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. {W}e aimed to quantify the cumulative incidence of switching to second-line {ART} among children in an international cohort collaboration. {M}ethods : {I}n 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 {C}ollaborative {I}nitiative for {P}aediatric {HIV} {E}ducation and {R}esearch ({CIPHER}) {G}lobal {C}ohort {C}ollaboration. {P}atients 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. {S}witch 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. {W}e 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. {F}indings : {A}t the data cutoff of {S}ept 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-{S}aharan {A}frica. {A}t {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. {M}edian 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}. {T}he 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 {CD}4 ({CD}4% or {CD}4 count) and viral load to 0.8% (0.6-1.0) in settings with clinical only monitoring. {I}n 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). {C}ohort-level factors that increased the likelihood of switching were higher-income country (p=0.0017) and routine or targeted monitoring of {CD}4 and viral load (p<0.0001), which was associated with a 166% increase in likelihood of switching compared with {CD}4 only monitoring (subdistributional hazard ratio 2.66, 95% {CI} 2.22-3.19). {I}nterpretation : {O}ur global paediatric analysis found wide variations in the incidence of switching to second-line {ART} across monitoring strategies. {T}hese findings suggest the scale-up of viral load monitoring would probably increase demand for paediatric second-line {ART} formulations. {C}opyright ({C}) 2019 {E}lsevier {L}td. {A}ll rights reserved.},
  keywords = {{MONDE}},
  booktitle = {},
  journal = {{T}he {L}ancet {HIV}},
  volume = {6},
  numero = {2},
  pages = {e105--e115 [+ 24 p.]},
  ISSN = {2352-3018},
  year = {2019},
  URL = {https://www.documentation.ird.fr/hor/fdi:010078291},
}