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NEUROPSYCHIATRIC OUTCOMES BEFORE AND AFTER SWITCHING TO DOLUTEGRAVIR-BASED THERAPY
Phillip Chan1, Orlanda Goh1, Eugène Kroon1, Donn J. Colby1, Carlo Sacdalan1, Suteeraporn Pinyakorn2, Somporn Tipsuk1, Nittaya Phanuphak1, Praphan Phanunphak3, Jintanat Ananworanich2, Victor Valcour4, Serena S. Spudich5, Robert Paul6
1SEARCH, Bangkok, Thailand,2US Military HIV Research Program, Bethesda, MD, USA,3Thai Red Cross AIDS Research Center, Bangkok, Thailand,4University of California San Francisco, San Francisco, CA, USA,5Yale University, New Haven, CT, USA,6University of Missouri St Louis, St Louis, MO, USA
Dolutegravir (DTG) is a 2nd generation HIV integrase inhibitor currently recommended as 1st-line antiretroviral therapy (ART). Neuropsychiatric (NP) adverse events have been reported with DTG but NP symptoms have not been systemically quantified using structured scales. This study examined mood and cognitive parameters before and after a planned transition from a non-DTG to a DTG-based regimen within a longitudinal study.
Participants on ≥ 24 weeks of ART started in acute HIV infection (AHI) underwent NP assessments before and after transition to DTG. They underwent: 1) Patient Health Questionnaire-9 (PHQ-9), a 9-item survey (score range 0-27) that evaluates both somatic and affective/cognitive symptoms of depression; 2) a 2-Questions screening that has been validated locally for major depression; 3) Distress Thermometer for anxiety/stress (scores 0-10); and 4) a 4-test battery that included Color Trails 1 and 2, Trails Making A and non-dominant hand grooved pegboard test. Outcomes before and after DTG were compared by McNemar and Wilcoxon signed-rank tests; multivariate linear regression examined factors that were correlated with the change of PHQ-9 scores.
256 individuals (95% male, median age 30 [IQR 25-36]) switched to DTG-based ART after a median 144 [IQR 24-192] weeks of ART (82% efavirenz-based) initiated in AHI. Serial assessments were done at median 19 [IQR 8-35] weeks before and median 37 [IQR 24-48] weeks after the switch. PHQ-9 scores were higher in 48% of participants, lower in 31%, and unchanged in 21% after switching. The proportion of participants with at least moderate depression symptoms (PHQ-9≥10) rose from 9% to 16% (p=0.007), while the percentage of those with moderately severe symptoms (PHQ-9≥15) did not change (3% vs. 3%). The PHQ-9 sub-scores of somatic symptoms (sleep/appetite/energy level) had a more significant increase than that of cognitive/affective symptoms (p=0.005 vs. p=0.052). Multivariate analysis showed that viral suppression (Mean difference -2.9, 95%CI [-0.9 to -5.0], p=0.005) and higher PHQ-9 scores (Mean difference -2.7, 95%CI [-1.2 to -4.2], p<0.001) prior to DTG were linked to decrease in PHQ-9 score after DTG. NPZ-4, CD4+ T-cell counts and CD4/CD8 ratio improved after DTG (Table).
DTG-associated NP adverse effects in this cohort were primarily related to somatic symptoms including insomnia, whereas there was no change in the prevalence of severe depressive symptoms or major depression.