What Should we do When HIV-Positive Children Fail First-Line Combination Antiretroviral Therapy? A Comparison of 4 ART Management Strategies
Managing virologic failure (VF) in HIV-infected children is especially difficult in resource-limited settings, given limited availability of alternative drugs, concerns around adherence and the development of HIV resistance mutations. We aimed to evaluate four management strategies for children foll...
Saved in:
Published in | The Pediatric infectious disease journal |
---|---|
Main Authors | , , , , , , , , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
01.04.2019
|
Online Access | Get more information |
Cover
Loading…
Abstract | Managing virologic failure (VF) in HIV-infected children is especially difficult in resource-limited settings, given limited availability of alternative drugs, concerns around adherence and the development of HIV resistance mutations. We aimed to evaluate four management strategies for children following their first episode of VF by comparing their immunologic and virologic outcomes.
We included children (aged <16 years) with VF from 8 IeDEA-SA cohorts, initiating cART between 2004-2010, who followed one of four management strategies: continuing on their failing regimen; switching to a second-line regimen; switching to a holding regimen (either lamivudine monotherapy or other non-cART regimen); discontinuing all ART. We compared the effect of management strategy on the 52-week change in CD4% and log10VL from VF, using inverse probability weighting of marginal structural linear models.
982 patients were followed over 54168 weeks. Relative to remaining on a failing regimen, switching to second-line showed improved immunologic and virologic responses 52 weeks after VF with gains in CD4% of 1.5% (95% CI 0.2-2.8) and declines in log10VL of -1.4 copies/mL (95% CI -2.0, -0.8), whilst switching to holding regimens or discontinuing treatment had worse immunologic (-5.4% (95% CI -12.1, 1.3) and -5.6% (95% CI -15.4, 4.1)) and virologic outcomes (0.2 (95% CI -3.6, 4.1) and 0.8 (95% CI -0.6, 2.1) respectively.
The results provide useful guidance for managing children with VF. Consideration should be given to switching children failing first-line cART to second-line, given the improved virologic and immune responses when compared with other strategies. |
---|---|
AbstractList | Managing virologic failure (VF) in HIV-infected children is especially difficult in resource-limited settings, given limited availability of alternative drugs, concerns around adherence and the development of HIV resistance mutations. We aimed to evaluate four management strategies for children following their first episode of VF by comparing their immunologic and virologic outcomes.
We included children (aged <16 years) with VF from 8 IeDEA-SA cohorts, initiating cART between 2004-2010, who followed one of four management strategies: continuing on their failing regimen; switching to a second-line regimen; switching to a holding regimen (either lamivudine monotherapy or other non-cART regimen); discontinuing all ART. We compared the effect of management strategy on the 52-week change in CD4% and log10VL from VF, using inverse probability weighting of marginal structural linear models.
982 patients were followed over 54168 weeks. Relative to remaining on a failing regimen, switching to second-line showed improved immunologic and virologic responses 52 weeks after VF with gains in CD4% of 1.5% (95% CI 0.2-2.8) and declines in log10VL of -1.4 copies/mL (95% CI -2.0, -0.8), whilst switching to holding regimens or discontinuing treatment had worse immunologic (-5.4% (95% CI -12.1, 1.3) and -5.6% (95% CI -15.4, 4.1)) and virologic outcomes (0.2 (95% CI -3.6, 4.1) and 0.8 (95% CI -0.6, 2.1) respectively.
The results provide useful guidance for managing children with VF. Consideration should be given to switching children failing first-line cART to second-line, given the improved virologic and immune responses when compared with other strategies. |
Author | Rabie, Helena Sipambo, Nosisa Giddy, Janet Nuttall, James Egger, Matthias Fairlie, Lee Eley, Brian Patten, Gabriela Seage, lll, George Tanser, Frank Essack, Gadija Sawry, Shobna Cotton, Mark Van Dyke, Russell B Boulle, Andrew Schomaker, Michael Davies, Mary-Ann Technau, Karl Patel, Kunjal Karalius, Brad van Zyl, Gert Wood, Robin |
Author_xml | – sequence: 1 givenname: Gabriela surname: Patten fullname: Patten, Gabriela organization: Centre for Infectious Disease Epidemiology & Research, University of Cape Town, Cape Town, South Africa – sequence: 2 givenname: Michael surname: Schomaker fullname: Schomaker, Michael organization: Centre for Infectious Disease Epidemiology & Research, University of Cape Town, Cape Town, South Africa – sequence: 3 givenname: Mary-Ann surname: Davies fullname: Davies, Mary-Ann organization: Centre for Infectious Disease Epidemiology & Research, University of Cape Town, Cape Town, South Africa – sequence: 4 givenname: Helena surname: Rabie fullname: Rabie, Helena organization: Tygerberg Academic Hospital, University of Stellenbosch – sequence: 5 givenname: Gert surname: van Zyl fullname: van Zyl, Gert organization: Division of Medical Virology, Stellenbosch University and National Health Laboratory Service, Tygerberg, Cape Town, South Africa – sequence: 6 givenname: Karl surname: Technau fullname: Technau, Karl organization: University of the Witwatersrand, Department of Paediatrics and Child Health, Rahima Moosa Mother and Child Hospital, Johannesburg, South Africa – sequence: 7 givenname: Brian surname: Eley fullname: Eley, Brian organization: Red Cross War Memorial Children's Hospital, and the Department of Paediatrics and Child Health, University of Cape Town, Cape Town, South Africa – sequence: 8 givenname: Andrew surname: Boulle fullname: Boulle, Andrew organization: Centre for Infectious Disease Epidemiology & Research, University of Cape Town, Cape Town, South Africa – sequence: 9 givenname: Russell B surname: Van Dyke fullname: Van Dyke, Russell B organization: Department of Pediatric, Tulane University, School of Medicine, New Orleans, United States – sequence: 10 givenname: Kunjal surname: Patel fullname: Patel, Kunjal organization: Harvard T.H. Chan School of Public Health, Department of Epidemiology, Centre for Biostatistics in AIDS Research (CBAR), Boston, United States – sequence: 11 givenname: Nosisa surname: Sipambo fullname: Sipambo, Nosisa organization: University of the Witwatersrand, Department of Paediatrics and Child Health, Chris Hani Baragwanath Academic Hospital, Johannesburg, South Africa – sequence: 12 givenname: Robin surname: Wood fullname: Wood, Robin organization: The Desmond Tutu HIV Centre, Institute for Infectious Disease & Molecular Medicine, University of Cape Town, Cape Town, South Africa – sequence: 13 givenname: Frank surname: Tanser fullname: Tanser, Frank organization: Africa Centre for Health and Population Studies, University of KwaZulu-Natal, Mtubatuba, South Africa – sequence: 14 givenname: Janet surname: Giddy fullname: Giddy, Janet organization: McCord Hospital, Durban, South Africa – sequence: 15 givenname: Mark surname: Cotton fullname: Cotton, Mark organization: Stellenbosch University and Tygerberg Children's Hospital, Department of Paediatrics and Child Health Division of Paediatric Infectious Diseases, Cape Town, South Africa – sequence: 16 givenname: James surname: Nuttall fullname: Nuttall, James organization: Red Cross War Memorial Children's Hospital, and the Department of Paediatrics and Child Health, University of Cape Town, Cape Town, South Africa – sequence: 17 givenname: Gadija surname: Essack fullname: Essack, Gadija organization: Tygerberg Academic Hospital, University of Stellenbosch – sequence: 18 givenname: Brad surname: Karalius fullname: Karalius, Brad organization: Harvard T.H. Chan School of Public Health, Department of Epidemiology, Centre for Biostatistics in AIDS Research (CBAR), Boston, United States – sequence: 19 givenname: George surname: Seage, lll fullname: Seage, lll, George organization: Harvard T.H. Chan School of Public Health, Department of Epidemiology, Centre for Biostatistics in AIDS Research (CBAR), Boston, United States – sequence: 20 givenname: Shobna surname: Sawry fullname: Sawry, Shobna organization: Wits Reproductive Health and HIV Institute, University of the Witwatersrand, Johannesburg, South Africa – sequence: 21 givenname: Matthias surname: Egger fullname: Egger, Matthias organization: Institute of Social and Preventive Medicine (ISPM), University of Bern, Bern, Switzerland – sequence: 22 givenname: Lee surname: Fairlie fullname: Fairlie, Lee organization: Wits Reproductive Health and HIV Institute, University of the Witwatersrand, Johannesburg, South Africa |
BackLink | https://www.ncbi.nlm.nih.gov/pubmed/30067598$$D View this record in MEDLINE/PubMed |
BookMark | eNpNUO9KwzAcDKI4N30DkbxAZ5qkzfpJyrBuMP-g030cv7a_rpE2GWk22Tv40FZU8L4c3B13cENybKxBQi5DNg5Zoq7nD9mY_QMPo_iInIWR4AFLJmpAhl333htChuyUDARjsYqSyRn5XNXg6Uttd01JP5CWlq5qNHQ2fwuebKe93iOd1ropXa9moBuaadf5YKFNb9g21wa8toamxmuH3tm9dtDQZY0Otocbmn6ntuB014dsRSVNn5f0HgxssEXTj3sHHjcau3NyUkHT4cUvj8hrdruczoLF4918mi6CQsQ8DlQpmIoUVLyKS1HkECFKzuJChlKJAhNRVGUkAVChymWFIc9VlUsGHPMYJB-Rq5_e7S5vsVxvnW7BHdZ_t_AvM21m0A |
CitedBy_id | crossref_primary_10_1093_ofid_ofz276 crossref_primary_10_1371_journal_pone_0282642 crossref_primary_10_1371_journal_pone_0242405 crossref_primary_10_1177_2049936120920177 |
ContentType | Journal Article |
CorporateAuthor | for IeDEA Southern Africa |
CorporateAuthor_xml | – name: for IeDEA Southern Africa |
DBID | NPM |
DOI | 10.1097/INF.0000000000002156 |
DatabaseName | PubMed |
DatabaseTitle | PubMed |
DatabaseTitleList | PubMed |
Database_xml | – sequence: 1 dbid: NPM name: PubMed url: https://proxy.k.utb.cz/login?url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database |
DeliveryMethod | no_fulltext_linktorsrc |
Discipline | Medicine |
EISSN | 1532-0987 |
ExternalDocumentID | 30067598 |
Genre | Journal Article |
GrantInformation_xml | – fundername: NIAID NIH HHS grantid: U01 AI069924 |
GroupedDBID | --- .-D .XZ .Z2 01R 0R~ 123 1J1 40H 4Q1 4Q2 4Q3 53G 5RE 5VS 71W 77Y 7O~ 8L- AAAAV AAAXR AAGIX AAHPQ AAIQE AAJCS AAMOA AAMTA AAQKA AARTV AASCR AASOK AAUEB AAXQO ABASU ABBUW ABDIG ABJNI ABPPZ ABVCZ ABXVJ ABZAD ACCJW ACDDN ACEWG ACGFS ACILI ACLDA ACWDW ACWRI ACXJB ACXNZ ADGGA ADHPY AE3 AE6 AEBDS AEETU AENEX AFDTB AFEXH AFSOK AFUWQ AGINI AHOMT AHQNM AHVBC AIJEX AINUH AJIOK AJNWD AJZMW AKULP ALMA_UNASSIGNED_HOLDINGS ALMTX AMJPA AMKUR AMNEI AOHHW AWKKM BOYCO BQLVK C45 CS3 DIWNM DU5 E.X EBS EEVPB EJD ERAAH EX3 F2K F2L F2M F2N F5P FCALG FL- GNXGY GQDEL H0~ HLJTE HZ~ IKREB IKYAY IN~ IPNFZ JK3 JK8 K8S KD2 KMI L-C N9A NPM N~7 N~B O9- OAG OAH ODA ODMTH OHYEH OJAPA OK1 OL1 OLG OLH OLU OLV OLW OLY OLZ OPUJH OVD OVDNE OVIDH OVLEI OVOZU OWU OWV OWW OWX OWY OWZ OXXIT P2P RIG RLZ S4R S4S SJN TEORI TSPGW V2I VVN W3M WOQ WOW X3V X3W XXN XYM YFH YOC |
ID | FETCH-LOGICAL-c3626-7d30757af2f6d3cba5ee4206c41473ce93cfd54aae7e7b4fe12b7fb40a2eb6a42 |
IngestDate | Wed Oct 16 00:50:10 EDT 2024 |
IsDoiOpenAccess | false |
IsOpenAccess | true |
IsPeerReviewed | true |
IsScholarly | true |
Language | English |
LinkModel | OpenURL |
MergedId | FETCHMERGED-LOGICAL-c3626-7d30757af2f6d3cba5ee4206c41473ce93cfd54aae7e7b4fe12b7fb40a2eb6a42 |
OpenAccessLink | https://boris.unibe.ch/119333/1/Patten%20PediatrInfectDisJ%202018_manuscript.pdf |
PMID | 30067598 |
ParticipantIDs | pubmed_primary_30067598 |
PublicationCentury | 2000 |
PublicationDate | 2019-April |
PublicationDateYYYYMMDD | 2019-04-01 |
PublicationDate_xml | – month: 04 year: 2019 text: 2019-April |
PublicationDecade | 2010 |
PublicationPlace | United States |
PublicationPlace_xml | – name: United States |
PublicationTitle | The Pediatric infectious disease journal |
PublicationTitleAlternate | Pediatr Infect Dis J |
PublicationYear | 2019 |
SSID | ssj0003410 |
Score | 2.3471563 |
Snippet | Managing virologic failure (VF) in HIV-infected children is especially difficult in resource-limited settings, given limited availability of alternative drugs,... |
SourceID | pubmed |
SourceType | Index Database |
Title | What Should we do When HIV-Positive Children Fail First-Line Combination Antiretroviral Therapy? A Comparison of 4 ART Management Strategies |
URI | https://www.ncbi.nlm.nih.gov/pubmed/30067598 |
hasFullText | |
inHoldings | 1 |
isFullTextHit | |
isPrint | |
link | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV1db9MwFLW6IU17QeP7W_cBnqxAGjtx84QqROgQrZDY0N4m27G1oS2dIGNiv2G_g9_Jdew0ZgwE9CGt7Cpqc4_uvbbPPZeQp3XOSsZLm3DHcOWMF8lEIpbHclJOWFojsF2B83xRzHb52718bzT6HrGWTlv1XJ9fWVfyP1bFMbSrq5L9B8uubooD-Bnti1e0MF7_ysZOd5t-OHBdqumZofWSom9t6Gz7Y_K-I2N9NV672FVrV_LwiFaHmO0l71xqiZ4AV8Xe_tOmRdfXuu2FULDvpAaesaqrWo86FVJOMQOOSDO0l7cNXMRPA_pWXUBWjK_TL_2BEI3_X3eC1bbeAb6RClfvR6to4WRCj2XgfsQk_yCR4N3cXH7-lkyboaxNKn_w0oVVGe9tjMuIEmN6f5wlaelj8i_e3qsIby8qr0IZXpjEFPHX0WYnxx0CmIvNue96_efZSxrc_dQaWRMT1yBk4faEQrzHPCDtizJL8eKqn7NJNvpbXFq-dGnMzha5HtYfMPVgukFGprlJNuaBYXGLXDhMgccUnBmol-AwBTGmoMcUOEzBgCmIMAU_YwoCpl7CFAZEwdICB0QUDIiCAVG3yW71eufVLAkdOxLtZI0SUWPIyIW0mS1qppXMjeFZWmg-5oJpUzJt65xLaYQRilszzpSwiqcyM6qQPLtD1ptlY-4RwHGpmciUqguMM7q0pbRCZ0Ibje_6Prnrn-P-iZdl2e-f8IPfzjwkmwPKHpFrFv2AeYxJZauedDb9AddseBY |
link.rule.ids | 780 |
linkProvider | National Library of Medicine |
openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=What+Should+we+do+When+HIV-Positive+Children+Fail+First-Line+Combination+Antiretroviral+Therapy%3F+A+Comparison+of+4+ART+Management+Strategies&rft.jtitle=The+Pediatric+infectious+disease+journal&rft.au=Patten%2C+Gabriela&rft.au=Schomaker%2C+Michael&rft.au=Davies%2C+Mary-Ann&rft.au=Rabie%2C+Helena&rft.date=2019-04-01&rft.eissn=1532-0987&rft_id=info:doi/10.1097%2FINF.0000000000002156&rft_id=info%3Apmid%2F30067598&rft_id=info%3Apmid%2F30067598&rft.externalDocID=30067598 |