PMID- 31891143
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220412
IS  - 2589-5370 (Electronic)
IS  - 2589-5370 (Linking)
VI  - 17
DP  - 2019 Dec
TI  - Immune reconstitution inflammatory syndrome in HIV infected late presenters 
      starting integrase inhibitor containing antiretroviral therapy.
PG  - 100210
LID - 10.1016/j.eclinm.2019.11.003 [doi]
LID - 100210
AB  - BACKGROUND: Integrase inhibitors (INI) induce a rapid decline of HIV-RNA in 
      plasma and CD4(+) T-cell recovery in blood. Both characteristics are also 
      associated with immune reconstitution inflammatory syndrome (IRIS). Whether the 
      use of INI-containing combination antiretroviral therapy (cART) increases the 
      risk of IRIS is being questioned. METHODS: Study within the Dutch ATHENA HIV 
      observational cohort. HIV-1 infected late presenters initiating cART after March 
      2009 were included if they had <200 CD4(+) T-cells per muL and were diagnosed with 
      an opportunistic infection. IRIS was defined either according to the criteria by 
      French et al. (IRIS(FRENCH)) or by a clinical IRIS diagnosis of the physician 
      (IRIS(CLINICAL)). The primary outcomes were the association between INI and the 
      occurrence of IRIS(FRENCH) and IRIS(FRENCH+CLINICAL) in multivariable logistic 
      regression. FINDINGS: 672 patients with a median CD4(+) T-cell count of 35 cells 
      per muL were included. Treatment with INI was independently associated with 
      IRIS(FRENCH) as well as IRIS(FRENCH+CLINICAL) (OR 2.43, 95%CI:1.45-4.07, and OR 
      2.17, 95%CI:1.45-3.25). When investigating INI separately, raltegravir (RAL) 
      remained significantly associated with IRIS(FRENCH) (OR 4.04 (95%CI:1.99-8.19) as 
      well as IRIS(FRENCH+CLINICAL) (OR 3.07, 95%CI:1.66-5.69), while dolutegravir 
      (DTG) became associated with IRIS(FRENCH+CLINICAL) after it replaced RAL as 
      preferred INI in the cohort after 2015 (OR 4.08, 95%CI:0.99-16.82, p=0.052). Too 
      few patients used elvitegravir to draw meaningful conclusions. Steroid initiation 
      for IRIS was more likely in those who initiated INI versus in those who did not, 
      but no increased hospital (re)admission or mortality rates were observed. 
      INTERPRETATION: In HIV late presenters from a resource rich setting, INI based 
      treatment initiation increased the risk of IRIS. This was observed for RAL and 
      DTG when being initiated as preferential INI in the presence of specific 
      AIDS-conditions, indicative of channeling bias. Although we controlled for all 
      relevant measured confounders, we cannot exclude that the observed association is 
      partially explained by residual confounding. INI use was not associated with 
      mortality nor hospitalization. Therefore, our observation is no reason to avoid 
      INI in late presenters. FUNDING: The ATHENA database is maintained by Stichting 
      HIV Monitoring and supported by a grant from the Dutch Ministry of Health, 
      Welfare and Sport through the Centre for Infectious Disease Control of the 
      National Institute for Public Health and the Environment.
CI  - (c) 2019 Published by Elsevier Ltd.
FAU - Wijting, Ingeborg E A
AU  - Wijting IEA
AD  - Department of Internal Medicine and Infectious Diseases, Erasmus MC, University 
      Medical Center Rotterdam, 's Gravendijkwal 230, 3015 CE, Rotterdam, the 
      Netherlands.
FAU - Wit, Ferdinand W N M
AU  - Wit FWNM
AD  - Stichting HIV Monitoring and Department of Global Health and Division of 
      Infectious Diseases, Amsterdam University Medical Centers, University of 
      Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands.
FAU - Rokx, Casper
AU  - Rokx C
AD  - Department of Internal Medicine and Infectious Diseases, Erasmus MC, University 
      Medical Center Rotterdam, 's Gravendijkwal 230, 3015 CE, Rotterdam, the 
      Netherlands.
FAU - Leyten, Eliane M S
AU  - Leyten EMS
AD  - Department of Internal Medicine and Infectious Diseases, Haaglanden Medical 
      Center, Lijnbaan 32, 2512 VH Den Haag, the Netherlands.
FAU - Lowe, Selwyn H
AU  - Lowe SH
AD  - Department of Internal Medicine and Infectious Diseases, Maastricht University 
      Medical Center, Debyelaan, 6229 HX Maastricht, the Netherlands.
FAU - Brinkman, Kees
AU  - Brinkman K
AD  - Department of Internal Medicine and Infectious Diseases, OLVG, Oosterpark 9, 1091 
      AC Amsterdam, the Netherlands.
FAU - Bierman, Wouter F W
AU  - Bierman WFW
AD  - Department of Internal Medicine/Infectious Diseases, University of Groningen, 
      University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, the 
      Netherlands.
FAU - van Kasteren, Marjo E E
AU  - van Kasteren MEE
AD  - Department of Internal Medicine and Infectious Diseases, ETZ, Hilvarenbeekse Weg 
      60, 5022 GC Tilburg, the Netherlands.
FAU - Postma, Anneloes M
AU  - Postma AM
AD  - Department of Internal Medicine and Infectious Diseases, Erasmus MC, University 
      Medical Center Rotterdam, 's Gravendijkwal 230, 3015 CE, Rotterdam, the 
      Netherlands.
FAU - Bloemen, Vera C M
AU  - Bloemen VCM
AD  - Department of Internal Medicine and Infectious Diseases, Erasmus MC, University 
      Medical Center Rotterdam, 's Gravendijkwal 230, 3015 CE, Rotterdam, the 
      Netherlands.
FAU - Bouchtoubi, Ghariba
AU  - Bouchtoubi G
AD  - Department of Internal Medicine and Infectious Diseases, Erasmus MC, University 
      Medical Center Rotterdam, 's Gravendijkwal 230, 3015 CE, Rotterdam, the 
      Netherlands.
FAU - Hoepelman, Andy I M
AU  - Hoepelman AIM
AD  - Department of Internal Medicine and Infectious Diseases, University Medical 
      Center Utrecht, University of Utrecht, Heidelberglaan 100, 3548 CX Utrecht, the 
      Netherlands.
FAU - van der Ende, Marchina E
AU  - van der Ende ME
AD  - Department of Internal Medicine and Infectious Diseases, Erasmus MC, University 
      Medical Center Rotterdam, 's Gravendijkwal 230, 3015 CE, Rotterdam, the 
      Netherlands.
FAU - Reiss, Peter
AU  - Reiss P
AD  - Stichting HIV Monitoring and Department of Global Health and Division of 
      Infectious Diseases, Amsterdam University Medical Centers, University of 
      Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands.
FAU - Rijnders, Bart J A
AU  - Rijnders BJA
AD  - Department of Internal Medicine and Infectious Diseases, Erasmus MC, University 
      Medical Center Rotterdam, 's Gravendijkwal 230, 3015 CE, Rotterdam, the 
      Netherlands.
CN  - ATHENA national observational HIV cohort
LA  - eng
PT  - Journal Article
DEP - 20191213
PL  - England
TA  - EClinicalMedicine
JT  - EClinicalMedicine
JID - 101733727
PMC - PMC6933261
OTO - NOTNLM
OT  - HIV
OT  - Immune reconstitution inflammatory syndrome
OT  - Integrase strand transfer inhibitor
OT  - Opportunistic infection
OT  - cART
EDAT- 2020/01/01 06:00
MHDA- 2020/01/01 06:01
PMCR- 2019/12/13
CRDT- 2020/01/01 06:00
PHST- 2019/05/19 00:00 [received]
PHST- 2019/10/01 00:00 [revised]
PHST- 2019/11/07 00:00 [accepted]
PHST- 2020/01/01 06:00 [entrez]
PHST- 2020/01/01 06:00 [pubmed]
PHST- 2020/01/01 06:01 [medline]
PHST- 2019/12/13 00:00 [pmc-release]
AID - S2589-5370(19)30209-3 [pii]
AID - 100210 [pii]
AID - 10.1016/j.eclinm.2019.11.003 [doi]
PST - epublish
SO  - EClinicalMedicine. 2019 Dec 13;17:100210. doi: 10.1016/j.eclinm.2019.11.003. 
      eCollection 2019 Dec.