TB Therapies Show Similar Neuropsychiatric Outcomes in HIV

The double dosing of dolutegravir and bictegravir HIV regimens in combination with rifampicin-based therapies for tuberculosis (TB) in people living with HIV showed similarly low levels of moderate to severe anxiety and depression, based on data from more than 100 adults. The findings were presented at the Conference on Retroviruses and Opportunistic Infections (CROI) 2025 Annual Meeting.

Previous research has suggested an increased risk for neuropsychiatric symptoms in people living with HIV who are being treated with INST (Integrase Strand Transfer) inhibitor antiretrovirals, Gillian L. Dorse, MD, of the Centre for AIDS Programme of Research in South Africa, and colleagues wrote in their abstract. For those also being treated for TB, the dose may be increased, but the impact on neuropsychiatric outcomes in this patient population has not been evaluated, the researchers noted.

In a secondary analysis of patients from the larger INSIGHT study, the researchers assessed whether giving the INST inhibitor dose twice daily resulted in higher rates of neuropsychiatric side effects including anxiety, depression, and sleep disturbance, co-author Kelly A. Dooley, MD, of Vanderbilt University, Nashville, Tennessee, said in an interview.

The modified intent-to-treat population included 122 adults with HIV and TB, randomized to receive bictegravir/emtricitabine/tenofovir alafenamide (BIC group, 80 patients) or tenofovir, lamivudine, dolutegravir (DTG group, 42 patients). The median age of the participants was 35 years, 65% were men. Approximately two thirds (60%) had baseline CD4 levels < 200 copies/mL.

Participants underwent neuropsychiatric assessments at 4, 8, 12, 24, 32, 40, and 48 weeks. Anxiety, depression, and sleep disturbance were assessed using the general anxiety disorder screening 7, patient health questionnaire, and a modified version of the global sleep assessment questionnaire.

No reports of severe anxiety or depression occurred in the DTG group of the study. Only one individual in the BIC group reported severe anxiety and depression in 2 days into treatment, but symptoms fully resolved after 5 days without the need for drug intervention or discontinuation of the study treatment, the researchers noted.

Low levels of moderate depression were reported in the BIC and DTG groups (1% and 5%, respectively), and no episodes of moderate level anxiety were reported in either group. Mild anxiety was reported in 3% and 10% of the BIC and DTG groups, respectively; 18% and 17% reported mild depression.

The infrequent development of neuropsychiatric symptoms among participants on-treatment compared with among those on pre-treatment baseline was encouraging news and supports the use of twice-daily bictegravir or twice-daily dolutegravir regimens among people with HIV and TB, Dooley told Medscape Medical News. “We look forward to introduction of bictegravir/emtricitabine/tenofovir alafenamide (Biktarvy) into more markets and further evaluation of outcomes among people with HIV-associated TB who receive this combination,” she said.

However, a majority of patients in the BIC and DTG groups (73% and 88%, respectively) reported sleep disruption (defined as sleep scores ≥ 6) and more research is needed to examine this association, the researchers noted.

The study received no outside funding. The researchers had no financial conflicts to disclose.