The effect of Biktarvy (B/F/TAF) on whole-body insulin sensitivity, lipid and endocrine profile in healthy volunteers.

Abstract

Background: Biktarvy is a single-tablet anti-retroviral regimen composed of a second-generation integrase-inhibitor (Bictegravir), in combination with tenofovir alafenamide and emtricitabine. Biktarvy has been shown to be highly effective in achieving and sustaining viral suppression. However, several studies have highlighted altered glycaemic control in individuals switching to Biktarvy from other regimens. The aim of this study was to quantify glucose disposal rates (GDR) in HIV-seronegative healthy volunteers following the administration of Biktarvy.

Method: A 72 day, open-label, two-arm, crossover, single-centre study. Participants were randomized 1:1 to either start 28 days of Biktarvy followed by 44 days without treatment (Group 1), or no treatment for 43 days followed by Biktarvy treatment for 28 days (Group 2). A hyper-insulinaemic-euglycaemic clamp was carried out at days 1, 28 and 72 with a 14-day washout period following the second clamp. Statistical assessments of change in estimated GDR were carried out using Wilcoxon signed-rank test (within-group) and Two-sample Wilcoxon rank-sum (Mann-Whitney) test (between-group). The primary study outcome was change from baseline in total body glucose disposal by euglycaemic clamp method following 28 days treatment.

Results: A total of 18 volunteers completed the study, with 11 in group 1 and seven in group 2. Within Group 1 the mean GDR was 7.52 mg/kg/min (SD 3.67) at baseline versus 8.50 mg/kg/min (SD 3.72) at day 28 (p = 0.32) and a mean percentage change of -13% (0.98). Within Group 2, the mean GDR was 6.54 mg/kg/min (SD 1.86) on day 28 versus 5.85 mg/kg/min (2.67) on day 72 (p-value = 0.38) mean percentage change -11% (-0.69). There was no statistically significant change between the groups at baseline (Mean 7.52 [SD 3.67] vs Mean 6.11 [SD 2.94], p-value = 0.31), at Day 28 (Mean 8.50 [SD 3.72] vs Mean 6.54 [SD 1.86], p-value = 0.27), or at Day 72 (Mean 9.65 [SD 5.07] vs Mean 5.85 [SD 2.67], p-value = 0.13). GDR on the final day of administration of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) was not significantly different (p = 0.104) between Group 1 Day 28 (6.64 [interquartile range (IQR) 5.83, 10.59] mg/kg/min) and Group 2 day 72 (0.28 [IQR 3.99, 8.79] mg/kg/min).

Conclusion: Treatment with Biktarvy for 28 days was not associated with a statistically significant impact on total body insulin sensitivity as measured using a hyper-insulinaemic-euglycaemic clamp method. However, long-term data on the metabolic effects of Biktarvy are needed.