Immune Reconstitution and Safe Metabolic Profile after the Switch to Bictegravir/Emtricitabine/Tenofovir Alafenamide Fumarate among Virologically Controlled PLWH: A 96 Week Update from the BICTEL Cohort

Abstract

Background: Bictegravir/emtricitabine/tenofovir alafenamide fumarate (BIC/FTC/TAF) is a recommended once-daily single-tablet regimen for the treatment of people living with HIV (PLWH). We aimed to assess efficacy, safety, and tolerability of BIC/FTC/TAF among PLWH, with a specific focus on people older than 55 years.

Methods: We recruited an observational retrospective real-life cohort, including all PLWH who underwent a therapeutic switch to BIC/FTC/TAF, independently from the previous treatment regimen (the BICTEL cohort). Longitudinal nonparametric analyses and linear models were built.

Results: After 96 weeks of follow-up, 164 PLWH were included, with 106 older than 55. Both the intention-to-treat and the per-protocol analysis showed low rates of virologic failure, independent of the pre-switch anchor drug. At week 96, a significant increase in CD4⁺ T cell count and in CD4⁺/CD8⁺ ratio was observed, inversely correlated with baseline immune status. Fasting serum lipid profile, total body weight, BMI, and hepatic function were not affected by the switch, without new onset of metabolic syndrome or weight gain. Compared to baseline, we observed a renal function worsening which is worthy of further follow-up.

Conclusion: BIC/FTC/TAF is an effective, safe, and well-tolerated switching strategy for PLWH, especially among those older than 55.

Keywords: BIC/FTC/TAF; HIV; antiretroviral; bictegravir; efficacy; immune reconstitution; real-life; safety; switch; tolerability.

Figure 1

(A) Virologic control (HIV-RNA < 50 copies/mL), virologic failure (HIV-RNA ≥ 50 copies /mL) and missing virologic data at week 48 (w48) and week 96 (w96). M = F: missing equal failure—intention-to-treat analysis; M = E: missing equal excluded—per-protocol analysis. No missing data were recorded at w48, thus the M = E and the M = F analyses are equal (red bar). At w96 missing data were recorded; thus, the figure shows bars for both the intention-to-treat analysis considering missing as failure (dark violet), and the per-protocol analysis treating missing as excluded (pale violet). (B) Virologic outcome at w48 and w96 according to FDA guidelines [14].

Figure 2

Genotypic profile of the 5 participants with RAMs at BL. 3TC: lamivudine; ABC: abacavir; AZT: zidovudine; BL: baseline; FTC: emtricitabine; p: participant; RAMs: resistance associated mutations; TFV: tenofovir.

Figure 3

Immune profile changes over time. The bars show the median relative difference from baseline (BL) for the considered immune parameters at both week 48 (w48) and week 96 (w96). The p-value shown under each bar comes from the paired Wilcoxon test between BL and the considered time-point; the p-value above-between the w48-bar and the w96-bar comes from the paired Wilcoxon test between w48 and w96. Vertical lines show the interquartile range. (A) Data from the overall BICTEL cohort. (B) Data only from PLWH older than 55 years.

Figure 4

Immune changes among time points as function of BL immune status. The figure visualizes the results of our linear regression model assessing the immune changes between time-points as function of the baseline (BL) immune status, [formula: median relative difference (MRD) = a + b*(BL CD4⁺ T cell count)]. The left column (A,D,G) shows the comparisons between BL and week 48 (w48); the middle column (B,E,H) shows the comparisons between week 96 (w96) and BL; the right column (C,F,I) shows the comparisons between w96 and w48. The upper row is relative to CD4⁺ T cells count; the middle row to CD8⁺ T cells count; the lower row is relative to CD4⁺/CD8⁺ ratio. The significant associations shown in (A,B,G,I) were confirmed at the multivariate analysis.

Figure 5

Metabolic changes over time. The bars show the median relative difference from baseline (BL) for the metabolic parameters considered at both week 48 (w48) and week 96 (w96). The p-value shown under each bar comes from the paired Wilcoxon test between BL and the considered time-point. The p-value above between the w48-bar and the w96-bar comes from the paired Wilcoxon test between w48 and w96. Vertical lines show the interquartile range. BMI: Body mass index; eGFR: Estimated glomerular filtrate rate, measured by the Chronic Kidney Disease Epidemiology Collaboration equation as mL/min/1.73 m²; TC: Total cholesterol; TC/HDL: Total cholesterol/LDL cholesterol ratio. (A,A1) Data from the overall BICTEL cohort. (B,B1) Data only from PLWH older than 55 years.