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AIDS Res Ther. 2020 Jan 7;17(1):1. doi: 10.1186/s12981-019-0257-8.

Neuropsychiatric outcomes before and after switching to dolutegravir-based therapy in an acute HIV cohort.

Author information

1
SEARCH, The Thai Red Cross AIDS Research Centre, Bangkok, Thailand.
2
The Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
3
United States Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
4
Department of Global Health, Amsterdam University Medical Centers, University of Amsterdam, and Amsterdam Institute for Global Health and Development, Amsterdam, The Netherlands.
5
Memory and Aging Center, Department of Neurology, University of California San Francisco, San Francisco, CA, USA.
6
Center for Neuroepidemiology and Clinical Neurological Research, Yale University, New Haven, CT, USA.
7
Missouri Institute of Mental Health, University of Missouri-St. Louis, St. Louis, MO, USA. Robert.Paul@mimh.edu.

Abstract

INTRODUCTION:

Dolutegravir (DTG)-based antiretroviral therapy (ART) is currently the first-line treatment for people living with HIV. Neuropsychiatric adverse events (NP-AEs) have been reported with DTG but neuropsychiatric symptoms have not been systemically quantified using structured scales. This study examined mood and cognitive parameters before and after a planned transition from non-DTG to DTG-based ART within a longitudinal study of acute HIV infection (AHI).

METHODS:

RV254 AHI cohort participants on ≥ 24 weeks of ART initiated at AHI underwent sequential assessments before and after the switch including: (1) Patient Health Questionnaire-9 (PHQ-9), a 9-item survey (scores 0-27) that evaluates somatic and affective/cognitive symptoms of depression; (2) a 2-Questions screening that has been validated locally for depression; (3) Distress Thermometer (scores 0-10); and 4) administration of a 4-test neurocognitive battery sensitive to HIV.

RESULTS:

254 individuals (95% male, median age 30) switched to a DTG-based regimen after a median 144 weeks of ART. Serial assessments were completed at a median of 19 weeks before and 37 weeks after DTG. There was a modest but statistically significant increase in PHQ-9 scores after DTG (pre-switch: 5 [IQR 1-7] vs. Post-switch: 5 [IQR 2-8], p = 0.009). The percentage of participants with at least moderate depression (PHQ-9 ≥ 10) increased from 10 to 16% (p = 0.006), but the frequency of moderate-severe depression (PHQ-9 ≥ 15) remained unchanged (3%). No volunteer reported NP-AEs within the study period. Somatic symptoms of depression increased more than cognitive/affective symptoms. Plasma viral suppression (HIV-1 RNA < 50; p = 0.005) and PHQ-9 ≥ 10 (p < 0.001) before switch were linked to lower PHQ-9 scores after DTG in multivariable analysis. Performance on all neuropsychological tests, except grooved pegboard test, improved modestly after DTG (all p < 0.05).

CONCLUSION:

After a median duration of 37 weeks of DTG use, there was a modest increase in the higher quartile of PHQ-9. This increase was associated with a rise in moderate depression symptoms but not the more severe forms of depression on PHQ-9. No clinically relevant NP-AEs were reported. Pre-existing depression was not associated with subsequent worsening of symptoms after DTG. Cognitive test performance improved post-DTG but could be due to practice effect.

KEYWORDS:

Cognitive performance; Depression; Dolutegravir; Neuropsychiatric adverse events; RV254

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