Background
Integrase strand transfer inhibitors (INSTI), such as dolutegravir and bictegravir, may be associated with neuropsychiatric symptoms in people living with HIV. Due to drug-drug interactions during co-treatment with rifampicin-based TB treatment, the dose of the INSTI is often doubled. However, the neuropsychiatric outcomes in people with TB/HIV during bictegravir double-dosing has not been evaluated.
Methods
We conducted a secondary analysis of the INSIGHT study (NCT04734652) and assessed neuropsychiatric outcomes in participants randomized to receive bictegravir/emtricitabine/tenofovir alafenamide (BIC arm) or tenofovir, lamivudine, dolutegravir (DTG arm).The bictegravir or dolutegravir regimens were dosed twice daily during TB treatment and once daily thereafter. Participants underwent regular follow-up, including neuropsychiatric assessments, at baseline and weeks 4, 8, 12, 24, 32,40 and 48. Self-reported anxiety, depression and sleep were assessed using the General anxiety disorder screener (GAD-7), Patient Health Questionnaire(PHQ-9) and a study modified Global Sleep Assessment Questionnaire (GSAQ) tools, respectively.
Results
A total of 122 adults with HIV and TB were enrolled, 80 in the BIC arm and 42 in the DTG arm. Median age was 35 years, 65% were male, and 60% had baseline CD4 < 200 copies/ml . Mild anxiety and depression were observed in 3% and 18% of individuals on BIC arm, and 10% and 17% on DTG (Table 1). Moderate depression was observed in 1% and 5% of BIC and DTG groups, respectively. One event of severe anxiety and depression occurred two days into treatment in the BIC arm, with full symptom resolution after five days with no drug intervention or study treatment discontinuation. Self-reported sleep disruption was noted with a sleep score of ≥ 6 and was reported in 73% of individuals in the BIC arm and 88% in the DTG arm.
Conclusions
The use of double-dose bictegravir was not significantly associated with a greater number of neuropsychiatric events than double-dose dolutegravir, and none of the identified events required neuropsychiatry interventions , treatment disruption or dose modifications in this study .