Increased Risk of Neuropsychiatric adverse events with Dolutegravir-based antiretroviral therapy During Pregnancy: Findings from a Prospective Cohort Study.

OBJECTIVES: Dolutegravir (DTG), a preferred antiretroviral therapy (ART) for Human Immunodeficiency Virus (HIV), is associated with neuropsychiatric adverse events (NPAEs) in adults, yet data in pregnant/breastfeeding women remains limited. We evaluated the prevalence and predictors of NPAE among pregnant and breastfeeding women receiving DTG-based ART regimens. METHODS: A prospective cohort of 163 pregnant women living with HIV (median age: 29 years; median ART duration: 30 months) on DTG + lamivudine + tenofovir disoproxil fumarate underwent neuropsychiatric assessments at baseline, during pregnancy, and postpartum (≤48 weeks post-delivery) using adjusted Mini-Mental State Examination (MMSE), Patient Health Questionnaire-9 (PHQ-9), and Generalized Anxiety Disorder-7 (GAD-7). The primary and secondary outcomes of the study were prevalence and incidence of NPAEs, respectively. Mixed-effects logistic regression identified predictors of NPAEs. RESULTS: Overall, 41.7% (95% CI: 34.1-49.7) of participants experienced at least one type of NPAE during the study period, being higher during pregnancy than postpartum (38.0% versus 11.0%, p = 0.008). Headache (19.6%), dizziness (16.0%), and cognitive impairment (12.9%) were most frequent. A 4.9-fold higher incidence of NPAE during pregnancy (29.5%, 2.5 cases/100 person-weeks) than postpartum (6%, 0.78 cases/100 person-weeks) was observed. Pregnancy (aOR: 2.43, 95% CI: 1.35-4.40) and HIV diagnosis during the current pregnancy (aOR: 5.38, 95% CI: 1.16-24.9) independently predicted NPAEs, while employment (aOR: 0.55, 95% CI: 0.25-0.99 and higher postpartum BMI (aOR: 0.86 per kg/m², 95% CI: 0.76-0.99) were protective. No ART discontinuations occurred. CONCLUSION: Pregnancy significantly increases the risk of DTG-related NPAEs. Proactive monitoring and timely interventions during antenatal care are recommended to support ART adherence, protect maternal mental health, and improve pregnancy and neonatal outcomes.