Paediatric integrase inhibitor use in a real-life setting: a single-centre cohort experience 2009-2018
File(s)CDIA-D-18-00421_accepted manuscript.pdf (2.05 MB)
Accepted version
Author(s)
Type
Journal Article
Abstract
Background and Objective
Integrase strand transfer inhibitors (INSTIs) have become the preferred first-line antiretroviral therapy in adults. There is paucity of published data on their use in children outside of clinical trials, particularly long-term safety and tolerability. This study aimed to describe INSTI use including the number of, and reasons for INSTI discontinuation.
Methods
We conducted a retrospective cohort analysis by database and electronic record review of children aged under 18 years with perinatally acquired human immunodeficiency virus who started INSTI-based antiretroviral therapy between May 2009 and March 2018, in a single tertiary centre.
Results
Fifty-six INSTI-based regimens were prescribed in 54 children, 64.9% from 2015 onwards. Twenty-one of 56 (37.5%) regimens commenced with raltegravir, 29 (51.8%) with dolutegravir and six (10.7%) with elvitegravir. The median age at the start of treatment was 15 years (interquartile range 13.5–16.4) with a median duration of INSTI-antiretroviral therapy of 1.65 years (range 0.01–8.8). Twenty-four children had a detectable viral load at the start INSTI therapy; 20 (83%) achieving viral suppression in a median of 26 days (interquartile range 19.5–34.5). There were 26 discontinuations of INSTI-based antiretroviral therapy after a median of 183 days; 9/26 because of adverse events. Four of nine adverse events were attributed to INSTI use, all in patients taking dolutegravir and the adverse events were neuropsychiatric and gastrointestinal in nature.
Conclusions
INSTI-based regimens were generally efficacious and well tolerated in this paediatric cohort, with 4/26 discontinuations due to INSTI-attributed adverse events. Further post-marketing surveillance of INSTI use in children is warranted.
Integrase strand transfer inhibitors (INSTIs) have become the preferred first-line antiretroviral therapy in adults. There is paucity of published data on their use in children outside of clinical trials, particularly long-term safety and tolerability. This study aimed to describe INSTI use including the number of, and reasons for INSTI discontinuation.
Methods
We conducted a retrospective cohort analysis by database and electronic record review of children aged under 18 years with perinatally acquired human immunodeficiency virus who started INSTI-based antiretroviral therapy between May 2009 and March 2018, in a single tertiary centre.
Results
Fifty-six INSTI-based regimens were prescribed in 54 children, 64.9% from 2015 onwards. Twenty-one of 56 (37.5%) regimens commenced with raltegravir, 29 (51.8%) with dolutegravir and six (10.7%) with elvitegravir. The median age at the start of treatment was 15 years (interquartile range 13.5–16.4) with a median duration of INSTI-antiretroviral therapy of 1.65 years (range 0.01–8.8). Twenty-four children had a detectable viral load at the start INSTI therapy; 20 (83%) achieving viral suppression in a median of 26 days (interquartile range 19.5–34.5). There were 26 discontinuations of INSTI-based antiretroviral therapy after a median of 183 days; 9/26 because of adverse events. Four of nine adverse events were attributed to INSTI use, all in patients taking dolutegravir and the adverse events were neuropsychiatric and gastrointestinal in nature.
Conclusions
INSTI-based regimens were generally efficacious and well tolerated in this paediatric cohort, with 4/26 discontinuations due to INSTI-attributed adverse events. Further post-marketing surveillance of INSTI use in children is warranted.
Date Issued
2019-06-01
Date Acceptance
2019-04-01
Citation
Clinical Drug Investigation, 2019, 39 (6), pp.585-590
ISSN
1173-2563
Publisher
Springer Verlag
Start Page
585
End Page
590
Journal / Book Title
Clinical Drug Investigation
Volume
39
Issue
6
Copyright Statement
© Springer Nature Switzerland AG 2019. The final publication is available at Springer via https://doi.org/10.1007/s40261-019-00783-8
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000470744100009&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Subjects
Science & Technology
Life Sciences & Biomedicine
Pharmacology & Pharmacy
ANTIRETROVIRAL THERAPY
HIV-1-INFECTED ADOLESCENTS
DOLUTEGRAVIR USE
ADVERSE EVENTS
EFFICACY
PHARMACOKINETICS
DISCONTINUATION
RALTEGRAVIR
REGIMENS
SAFETY
Publication Status
Published
Date Publish Online
2019-04-11