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 and breastfeeding women remains limited. We evaluated the prevalence and predictors of NPAEs 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 the 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.