Nicole Ngo-Giang-Huong, Linda Wittkop, Ali Judd, Peter Reiss, Tessa Goetghebuer, Dan Duiculescu, Antoni Noguera-Julian, Magdalena Marczynska, Carlo Giacquinto, Luminita Ene, Jose T. Ramos, Cristina Cellerai, Thomas Klimkait, Benedicte Brichard, Niels Valerius, Caroline Sabin, Ramon Teira, Niels Obel, Christoph Stephan, Stephane de Wit, Claire Thorne, Diana Gibb, Christine Schwimmer, Maria Athena Campbell, Deenan Pillay, Marc Lallemant
- Background: Few studies have evaluated the impact of pre-treatment drug resistance (PDR) on response to combination antiretroviral treatment (cART) in children. The objective of this joint EuroCoord-CHAIN-EPPICC/PENTA project was to assess the prevalence of PDR mutations and their association with virological outcome in the first year of cART in children.
Methods: HIV-infected children <18 years initiating cART between 1998 and 2008 were included if having at least one genotypic resistance test prior to cART initiation. We used the World Health Organization 2009 resistance mutation list and Stanford algorithm to infer resistance to prescribed drugs. Time to virological failure (VF) was defined as the first of two consecutive HIV-RNA > 500 copies/mL after 6 months cART and was assessed by Cox proportional hazards models. All models were adjusted for baseline demographic, clinical, immunology and virology characteristics and calendar period of cART start and initial cART regimen.
Results: Of 476 children, 88 % were vertically infected. At cART initiation, median (interquartile range) age was 6.6 years (2.1–10.1), CD4 cell count 297 cells/mm3 (98–639), and HIV-RNA 5.2 log10copies/mL (4.7–5.7). Of 37 children (7.8 %, 95 % confidence interval (CI), 5.5–10.6) harboring a virus with ≥1 PDR mutations, 30 children had a virus resistant to ≥1 of the prescribed drugs. Overall, the cumulative Kaplan-Meier estimate for virological failure was 19.8 % (95 %CI, 16.4–23.9). Cumulative risk for VF tended to be higher among children harboring a virus with PDR and resistant to ≥1 drug prescribed than among those receiving fully active cART: 32.1 % (17.2–54.8) versus 19.4 % (15.9–23.6) (P = 0.095). In multivariable analysis, age was associated with a higher risk of VF with a 12 % reduced risk per additional year (HR 0.88; 95 %CI, 0.82–0.95; P < 0.001).
Conclusions: PDR was not significantly associated with a higher risk of VF in children in the first year of cART. The risk of VF decreased by 12 % per additional year at treatment initiation which may be due to fading of PDR mutations over time. Lack of appropriate formulations, in particular for the younger age group, may be an important determinant of virological failure.
MetadatenAuthor: | Nicole Ngo-Giang-HuongORCiD, Linda Wittkop, Ali JuddORCiD, Peter ReissORCiD, Tessa Goetghebuer, Dan Duiculescu, Antoni Noguera-JulianORCiD, Magdalena Marczynska, Carlo Giacquinto, Luminita Ene, Jose T. Ramos, Cristina Cellerai, Thomas Klimkait, Benedicte Brichard, Niels Valerius, Caroline SabinORCiDGND, Ramon Teira, Niels Obel, Christoph StephanORCiDGND, Stephane de Wit, Claire Thorne, Diana Gibb, Christine Schwimmer, Maria Athena Campbell, Deenan Pillay, Marc Lallemant |
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URN: | urn:nbn:de:hebis:30:3-457824 |
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DOI: | https://doi.org/10.1186/s12879-016-1968-2 |
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ISSN: | 1471-2334 |
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Pubmed Id: | https://pubmed.ncbi.nlm.nih.gov/27825316 |
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Parent Title (English): | BMC infectious diseases |
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Publisher: | BioMed Central ; Springer |
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Place of publication: | London ; Berlin ; Heidelberg |
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Document Type: | Article |
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Language: | English |
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Year of Completion: | 2016 |
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Date of first Publication: | 2016/11/08 |
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Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
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Contributing Corporation: | The EuroCoord-CHAIN-EPPICC joint project study group |
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Release Date: | 2018/03/01 |
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Tag: | Children; First-line combination antiretroviral therapy; HIV; Pre-treatment drug resistance mutations; Virological failure |
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Volume: | 16 |
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Issue: | 1, Art. 654 |
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Page Number: | 10 |
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First Page: | 1 |
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Last Page: | 10 |
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Note: | Open Access: This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
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HeBIS-PPN: | 431861390 |
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Institutes: | Medizin / Medizin |
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Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
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Sammlungen: | Universitätspublikationen |
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Licence (German): | Creative Commons - Namensnennung 4.0 |
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