PMID- 27860104
OWN - NLM
STAT- MEDLINE
DCOM- 20170802
LR  - 20220409
IS  - 1468-1293 (Electronic)
IS  - 1464-2662 (Linking)
VI  - 18
IP  - 1
DP  - 2017 Jan
TI  - Higher rates of neuropsychiatric adverse events leading to dolutegravir 
      discontinuation in women and older patients.
PG  - 56-63
LID - 10.1111/hiv.12468 [doi]
AB  - OBJECTIVES: Dolutegravir (DTG), a second-generation integrase strand transfer 
      inhibitor (INSTI), is now among the most frequently used antiretroviral agents. 
      However, recent reports have raised concerns about potential neurotoxicity. 
      METHODS: We performed a retrospective analysis of a cohort of HIV-infected 
      patients who had initiated an INSTI in two large German out-patient clinics 
      between 2007 and 2016. We compared discontinuation rates because of adverse 
      events (AEs) within 2 years of starting treatment with dolutegravir, raltegravir 
      or elvitegravir/cobicistat. We also evaluated factors associated with 
      dolutegravir discontinuation. RESULTS: A total of 1950 INSTI-based therapies were 
      initiated in 1704 patients eligible for analysis within the observation period. 
      The estimated rates of any AE and of neuropsychiatric AEs leading to 
      discontinuation within 12 months were 7.6% and 5.6%, respectively, for 
      dolutegravir (n = 985), 7.6% and 0.7%, respectively, for elvitegravir (n = 287), 
      and 3.3% and 1.9%, respectively, for raltegravir (n = 678). Neuropsychiatric AEs 
      leading to dolutegravir discontinuation were observed more frequently in women 
      [hazard ratio (HR) 2.64; 95% confidence interval (CI) 1.23-5.65; P = 0.012], in 
      patients older than 60 years (HR: 2.86; 95% CI: 1.42-5.77; P = 0.003) and in 
      human leucocyte antigen (HLA)-B*5701-negative patients who initiated abacavir at 
      the same time (HR: 2.42; 95% CI: 1.38-4.24; P = 0.002). CONCLUSIONS: In this 
      large cohort, the rate of discontinuation of dolutegravir because of 
      neuropsychiatric adverse events was significantly higher than for other INSTIs, 
      at almost 6% within 12 months. Despite the limitations of this retrospective 
      study, the almost three-fold higher discontinuation rates observed amongst women 
      and older patients underscore the need for further investigation, especially in 
      patient populations usually underrepresented in clinical trials.
CI  - (c) 2016 British HIV Association.
FAU - Hoffmann, C
AU  - Hoffmann C
AD  - ICH Study Center Hamburg, Hamburg, Germany.
AD  - Department of Medicine II, University of Schleswig-Holstein, Kiel, Germany.
FAU - Welz, T
AU  - Welz T
AD  - Praxis am Ebertplatz, Cologne, Germany.
FAU - Sabranski, M
AU  - Sabranski M
AD  - ICH Study Center Hamburg, Hamburg, Germany.
FAU - Kolb, M
AU  - Kolb M
AD  - Praxis am Ebertplatz, Cologne, Germany.
AD  - Department I of Internal Medicine, University Hospital Cologne, Cologne, Germany.
FAU - Wolf, E
AU  - Wolf E
AD  - MUC Research GmbH, Munich, Germany.
FAU - Stellbrink, H-J
AU  - Stellbrink HJ
AD  - ICH Study Center Hamburg, Hamburg, Germany.
FAU - Wyen, C
AU  - Wyen C
AD  - Praxis am Ebertplatz, Cologne, Germany.
AD  - Department I of Internal Medicine, University Hospital Cologne, Cologne, Germany.
LA  - eng
PT  - Journal Article
DEP - 20161110
PL  - England
TA  - HIV Med
JT  - HIV medicine
JID - 100897392
RN  - 0 (HIV Integrase Inhibitors)
RN  - 0 (Heterocyclic Compounds, 3-Ring)
RN  - 0 (Oxazines)
RN  - 0 (Piperazines)
RN  - 0 (Pyridones)
RN  - DKO1W9H7M1 (dolutegravir)
SB  - IM
CIN - HIV Med. 2018 May;19(5):e62-e63. PMID: 28762661
MH  - Adolescent
MH  - Adult
MH  - Age Factors
MH  - Aged
MH  - Aged, 80 and over
MH  - Drug-Related Side Effects and Adverse Reactions/epidemiology
MH  - Female
MH  - Germany
MH  - HIV Infections/*drug therapy
MH  - HIV Integrase Inhibitors/*adverse effects/*therapeutic use
MH  - Heterocyclic Compounds, 3-Ring/*adverse effects/*therapeutic use
MH  - Humans
MH  - Male
MH  - Mental Disorders/*chemically induced/*epidemiology
MH  - Middle Aged
MH  - Outpatients
MH  - Oxazines
MH  - Piperazines
MH  - Pyridones
MH  - Retrospective Studies
MH  - Sex Factors
MH  - Withholding Treatment
MH  - Young Adult
OTO - NOTNLM
OT  - HIV infection
OT  - adverse events
OT  - antiretroviral therapy
OT  - dolutegravir
OT  - integrase inhibitors
OT  - side effects
EDAT- 2016/11/20 06:00
MHDA- 2017/08/03 06:00
CRDT- 2016/11/19 06:00
PHST- 2016/09/06 00:00 [accepted]
PHST- 2016/11/20 06:00 [pubmed]
PHST- 2017/08/03 06:00 [medline]
PHST- 2016/11/19 06:00 [entrez]
AID - 10.1111/hiv.12468 [doi]
PST - ppublish
SO  - HIV Med. 2017 Jan;18(1):56-63. doi: 10.1111/hiv.12468. Epub 2016 Nov 10.