Short-Term Neuropsychiatric Tolerability of Bictegravir Combined with Emtricitabine/Tenofovir Alafenamide in Clinical Practice

Abstract

Background Neuropsychiatric AEs (NPAEs) leading to dolutegravir (DTG) discontinuation were seen more frequently in real-world use than in randomized clinical trials (RCTs). The recently approved fixed-dose combination bictegravir plus emtricitabine and tenofovir alafenamide (BIC/F/TAF) has shown comparable NPAE rates but some favourable patient-reported outcomes in RCTs compared with DTG. We were interested in its neuropsychiatric tolerability in clinical practice. Methods All patients starting BIC/F/TAF from June 2018 in a single centre (two subcentres) were followed retrospectively. Discontinuation rates due to any AEs and NPAEs were compared with those of patients initiating DTG-based regimens. Results As of May 2019, a total of 943 patients (852 males, 76 females, 15 transgender and gender diverse) initiated BIC/F/TAF outside RCTs. After a median follow-up of 6.2 months, 50 (5.3%) and 31 (3.3%) patients had discontinued BIC/F/TAF due to any AEs or to NPAEs, respectively. In multivariate analysis, a pre-existing depression and subcentre remained predictive for NPAEs, but not age, gender, ethnicity or prior DTG-related AEs. Compared with 1,043 patients treated with DTG-based regimens, the estimated NPAE-related discontinuation rate with BIC/F/TAF was comparable during the first 6 months (P=0.36). Cross-intolerance was low, and only 5/55 patients with prior DTG intolerability had to discontinue BIC/F/TAF due to NPAEs. Conclusions Short-term tolerability of BIC/F/TAF was comparable to DTG-containing regimens. As seen with DTG, discontinuation rates were higher than in RCTs. A pre-existing depression but also physician's awareness may have an impact on tolerability and continuation of BIC/F/TAF. In contrast, prior intolerability of DTG was of limited predictive value.

The burden of neuropsychiatric disorders in patients living with HIV-1 treated with antiretroviral therapies—A perspective from US Medicaid data

“…12 Conversely, in analysis of routine clinical care, treatment discontinuation rates due to neuropsychiatric events were comparable between dolutegravir and bictegravir (P = 0.31). 14 These findings underscore the importance of selecting an initial ART regimen that does not have the propensity to cause or worsen NPEs. Data from a recent analysis of a phase 3 study of treatment-naïve patients starting a darunavir-based single-tablet regimen showed that patients with baseline neuropsychiatric comorbidities, versus those without, did not experience a higher incidence of new-onset study drug-related neurologic (5% in both cohorts) or psychiatric (1% vs 3%) adverse events, suggesting that a darunavir-based singletablet regimen may be a suitable option for this patient population.…”

“…10 Certain ART regimens have been associated with an increased risk of NPEs, but the extent varies even among agents in the same class. 1,5,[11][12][13][14] Findings from a phase 3b equivalence study evaluating ritonavir-boosted atazanavir versus efavirenz indicate that ritonavir-boosted atazanavir had a lower incidence of neuropsychological adverse events, including depression, dizziness/lightheadedness, and insomnia than efavirenz across two different nucleoside reverse transcriptase inhibitor backbones. 15 In a pooled analysis of phase 3 studies of two non-nucleoside reverse transcriptase inhibitor-based regimens, the incidence of treatment-related neuropsychiatric adverse events was significantly higher with efavirenz than rilpivirine (any cause: 57% vs 40%, P < 0.0001; treatment-related: 48% vs 27%, P < 0.0001).…”

“…11 Among integrase inhibitors, the observed neuropsychiatric safety of dolutegravir has been similar to other integrase inhibitors in some studies, but reduced in others. 1,5,[12][13][14] In an analysis of data from both clinical trials and an electronic medical records database, dolutegravir-treated patients reported low rates of psychiatric events, similar to patients using raltegravir, elvitegravir, HIV, human immunodeficiency virus; NPE, neuropsychiatric event.…”

Viro-Immunological, Clinical Outcomes and Costs of Switching to BIC/TAF/FTC in a Cohort of People Living with HIV: A 48-Week Prospective Analysis

“…Most cohort studies reported a higher rate of discontinuation of DTG due to neuropsychiatric adverse events in comparison with other INSTIs. However, a recent study showed that the short-term tolerability of BIC/FTC/TAF was comparable to DTG-containing regimens, with a low rate of cross-intolerance between the two INSTIs [ 31 ].…”

Reversibility of Central Nervous System Adverse Events in Course of Art

“…For other INSTIs such as raltegravir (RAL) and elvitegravir (EVG), the incidence of CNS toxicity reports seems lower in the literature [ 22 , 23 ]. At the same time, for bictegravir (BIC), observational data are still scarce [ 24 ], but for all of them, CNS-AEs have been signaled in the literature with variable incidence [ 24 , 25 , 26 , 27 ].…”