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

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.

Antiretroviral Treatment Failure and Associated Factors Among HIV-Infected Children on Antiretroviral Therapy: A Retrospective Study

“…The risk of treatment failure was nine times higher among patients those changed ART regimen as compared to those who did not change ART regimen (AOR = 9.22: 95% (3.36–25.03)). This finding was in agreement with previous studies conducted in Ethiopia 19 , 21 , 22 , 37 and Malawi. 30 This might be due to the patient clinical background/condition that may force them to change the regimen.…”

“…Children who had been on long-duration of ART treatment had a higher risk of treatment failure than their counterparts (AOR=1.47: 95% (1.34–2.89)). This finding was in line with previous studies conducted in Ethiopia 11 , 37 , 38 and Bangalore. 39 The possible reason could be if the duration of ART increases, the emergence of HIV-drug resistance mutation and persistent HIV- replication occurred.…”

“…Thus, a high burden of a drug-resistant virus with an increased viral load is expected among patients with more months than with lesser months on ART. 37 , 41 Those who took the drug for a long duration of time may develop drug side effects and resistance easily.…”

Antiretroviral Drugs Impact Autophagy with Toxic Outcomes

“…No single antiretroviral drug nor drug combination can eliminate the virus from the body, thus necessitating life-long treatment. Therefore, long-term toxicity remains a concern for PLWH, and even relatively new antiretroviral drugs have burdensome side effects [ 3 , 4 , 5 ].…”

High-content analysis and Kinetic Image Cytometry identify toxic and epigenotoxic effects of HIV antiretrovirals on human iPSC-neurons and primary neural precursor cells

“…EFV (NNRTI) is linked neuropsychiatric effects (e.g., nightmares, dizziness, depression) and cognitive impairment [21][22][23] . Dolutegravir (DTG) is also linked to neuropsychiatric effects (sleep disturbance, depression) [24][25][26][27] . Because of the reservoir of HIV in the CNS, there has been increased effort to improve the penetrance of ARVs into the CNS.…”