Bictegravir/Emtricitabine/Tenofovir Alafenamide Treatment: Efficacy and Tolerability in Clinical Practice

Figures & data

Figure 1 Flowchart of data extraction.

Table 1 Characteristics of Patients Included in the Analysis at the Time of BFTAF Treatment Initiation

Variable	Overall (n=1040)	Switch FROM ECFTAF (n=705)	Switch from Other Regimens (n=335)
Age (years)	51.1 (42–57.1)	49.5 (40.5–56.2)	53.5 (44.8–58.5)
Male gender	854 (82.1%)	596 (84.5%)	258 (77%)
HIV risk factor
MSM	532 (51.2%)	392 (55.6%)	140 (41.8%)
PWID	120 (11.5%)	58 (8.2%)	62 (18.5%)
Heterosexual	201 (19.3%)	122 (17.3%)	79 (23.6%)
Other (blood transfusion, MTCT, unknown)	187 (18.0%)	133 (18.9%)	54 (16.1%)
Years since HIV diagnosis	13.8 (6.8–23.4)	12.7 (6.7–20.5)	19.3 (7–27.9)
Years of ART	10.2 (5.1–19.7)	9.2 (5.1–17.2)	13.9 (5.1–22.7)
Nadir CD4+ lymphocytes (cells/µL)	291 (166–447)	308 (173–460)	258 (133–419)
HCV IgG positive test	212 (20.4%)	120 (17%)	92 (27.5%)
HBsAg positive test	82 (7.9%)	52 (7.4%)	30 (9%)
AIDS diagnosis	181 (17.4%)	99 (14%)	82 (24.5%)
Type of previous ART
3-drug PI-based	56 (5.4%)	0 (0%)	56 (16.7%)
3-drug NNRTI-based	38 (3.7%)	0 (0%)	38 (11.7%)
3-drug InSTI-based	899 (87.4%)	705 (100%)	194 (59.9%)
Other regimens	47 (4.5%)	0 (0%)	47 (14%)
CD4+ (cells/µL)	718 (535–941)	732 (535–955)	697 (532–904)
CD8+ (cells/µL)	827 (605–1128)	834 (614–1142)	807 (580–1088)
CD4+ (%)	32.4 (26.5–39.3)	32.7 (26.7–39.3)	32 (25.5–39.3)
CD8+ (%)	36.3 (29.9–44.1)	37 (30.2–44.2)	35.2 (29.5–43.6)
CD4+/CD8+ ratio	0.91 (0.62–1.24)	0.91 (0.63–1.22)	0.93 (0.61–1.27)
Platelets (10^9/L)	227 (192–269)	227 (196–270)	224 (189–264)
Haemoglobin (g/dL)	15.1 (14.2–16)	15.2 (14.3–16)	14.9 (14–16)
White blood cells (10^9/L)	6.4 (5.3–7.6)	6.4 (5.3–7.7)	6.2 (5.4–7.4)
Total lymphocytes (10^9/L)	2.2 (1.8–2.8)	2.3 (1.8–2.8)	2.2 (1.8–2.7)
Total neutrophils (10^9/L)	3.3 (2.5–4.1)	3.2 (2.4–4.2)	3.3 (2.5–4)
Creatinine (mg/dL)	1.04 (0.91–1.16)	1.04 (0.91–1.16)	1.04 (0.91–1.18)
eGFR (mL/min/1.73m2)	81 (69–94)	82 (72–95)	78 (65–91)
Glucose (mg/dL)	94 (87–102)	93 (86–100)	95 (88–106)
Triglycerides (mg/dL)	116 (85–160)	116 (86–163)	114 (82–157)
Total cholesterol (mg/dL)	186 (165–213)	189 (169–215)	184 (158–209)
HDL cholesterol (mg/dL)	50 (43–59)	51 (43–59)	49 (42–59)
LDL cholesterol (mg/dL)	124 (103–147)	126 (105–149)	120 (99.5–144.5)
ALT (U/L)	24 (19–34)	24 (18–33)	26 (19–35)
AST (U/L)	25 (21–30)	24 (20–29)	26 (21–32)
Fib-4 index	1.07 (0.78–1.47)	1.01 (0.77–1.39)	1.19 (0.83–1.62)

Abbreviations: MSM, Men who have Sex with Men; PWID, People Who Inject Drugs; MTCT, Mother-To-Child Transmission; PI, Protease Inhibitor; NNRTI, Non-Nucleoside Reverse Transcriptase Inhibitor; InSTI, Integrase Strand Transfer Inhibitor; eGFR, estimated Glomerular Filtration Rate; Fib-4, Fibrosis-4 index for liver fibrosis.

Figure 2 Probability of virological failure, Kaplan–Meier curve.

Table 2 Results of Genotypic Resistance Tests (GRTs) Available on Partially or Completely Amplifiable Samples

ID and Type of Sample	VL at VF (cp/mL)	Months to VF	InSTI RAMs	NRTI RAMs	Other RAMs	Follow-Up	Potential Reason of VF
1. RNA	319	31.5	Na	None	K20R	Spontaneous stable VS in BFTAF	Recent vaccination
2. RNA	81	10.4	None	None	PI na	LLV in BFTAF	Not identified
3. RNA	1570	2.9	None	Na	None	Spontaneous stable VS in BFTAF	Not identified
4. RNA + DNA	201	11.5	None	None	None	Spontaneous stable VS in BFTAF	DDIs (mineral supplements containing Mg)
5. RNA + DNA	168	15.5	None	None	K103N*	Switch to DTG+DcFTAF	Suspected HIV-1/2 co-infection

Note: *Present since pre-ART GRT.

Abbreviations: VL, viral load; VF, virological failure; cp, copies; InSTI, Integrase Strand Transfer Inhibitor; NRTI, Nucleoside Reverse Transcriptase Inhibitor; RAMs, resistance associated mutations; na, not amplifiable; VS virological suppression; PI, Protease Inhibitor; LLV, low-level viremia defined as a confirmed detectable HIV-RNA level <200 cp/mL according to DHHS 2021 Guidelines; DTG, dolutegravir; DcFTAF, darunavir/cobicistat/emtricitabine/tenofovir alafenamide.

Figure 3 Probability of discontinuing BFTAF, Kaplan–Meier curve.

Figure 4 Probability of treatment failure, Kaplan–Meier curve.

Table 3 Monthly Changes of Some Parameters of Interest After Starting BFTAF

Variable	Mean Change per Month of Change FROM BL (95% Confidence Interval)	P value
CD4+ lymphocytes (cells/µL)	0.51 (0.058; 0.97)	0.027
CD4+ lymphocytes (%)	0.035 (0.025; 0.045)	<0.0001
CD4+ and CD8+ ratio	0.001 (0.0004; 0.0015)	0.0008
Haemoglobin (g/dL)	0.006 (0.004; 0.009)	<0.0001
Total neutrophils (10^9/L)	0.006 (0.002; 0.009)	0.001
Creatinine (mg/dL)	0.001 (0.0007; 0.0015)	<0.0001
eGFR (mL/min/1.73m2)	−0.135 (−0.161; −0.110)	<0.0001
Glucose (mg/dL)	0.108 (0.063; 0.152)	<0.0001
Triglycerides (mg/dL)	−0.344 (−0.507; −0.181)	<0.0001
Total cholesterol (mg/dL)	−0.106 (−0.185; −0.028)	0.008
HDL cholesterol (mg/dL)	−0.043 (−0.067; −0.019)	0.0005
LDL cholesterol (mg/dL)	−0.407 (−0.485; −0.328)	<0.0001
Fib-4 Index	0.006 (0.004; 0.008)	<0.0001

Abbreviations: BFTAF, bictegravir/emtricitabine/tenofovir alafenamide; BL, baseline; eGFR, estimated Glomerular Filtration Rate; HDL, High-density lipoproteins; LDL, Low-density lipoproteins; Fib-4, Fibrosis-4 index for liver fibrosis.