Early discontinuation of DTG/ABC/3TC and BIC/TAF/FTC single-tablet regimens: a real-life multicenter cohort study

Figures & data

Table 1 Clinical/demographic baseline characteristics and outcome of HIV-1 infected, ART-experienced patients with HIV-RNA level <50 copies/mL switching to BIC/TAF/FTC or to DTG/ABC/3TC in five centers in Italy

	BIC/TAF/FTC (262)		DTG/ABC/3TC (524)		p
Baseline characteristics
Italian origin, n (%)	221	(84.3)	431	(82.2)	0.502
Male sex at birth, n (%)	206	(78.6)	385	(73.5)	0.171
Age at entry (years), median [IQR]	54	[44–60]	51	[41–57]	0.003
Route of HIV transmission, n (%)					0.044
Heterosexual unprotected sex	75	(28.6)	203	(38.7)
MSM	121	(46.2)	212	(40.5)
IVDU	36	(13.7)	63	(12.0)
Other	6	(2.0)	0.4
Not known	24	(9.1)	44	(8.4)
Months of undetectable viremia, median [IQR]	51	[24–106]	42	[14–98]	0.006
Cardiovascular disease, n (%)	56	(21.4)	71	(13.6)	0.005
Neuropsychiatric illness, n (%)	17	(6.5)	12	(2.3)	0.003
Diabetes, n (%)	14	(5.3)	13	(2.5)	0.038
Chronic kidney disease, n (%)	6	(2.3)	4	(0.8)	0.072
Dyslipidemia, n (%)	32	(12.2)	30	(5.7)	0.001
Patients with at least one comorbidity, n (%)	115	(43.9)	117	(22.3)	<0.001
AIDS diagnosis, n (%)	54	(20.6)	86	(16.4)	0.147
HCV Ab positivity, n (%)	47	(17.9)	93	(17.7)	0.947
HIV RNA Zenit (copies/mL) Log10, median [IQR]	5.1	[4.7–5.6]	5.1	[4.6–6.0]	0.5094
Nadir CD4 (cells/mL), median [IQR]	230	[110–342]	219	[77–353]	0.6184
Years since HIV diagnosis, median [IQR]	13	[5–22]	10	[4–19]	0.0081
Years of antiretroviral therapy, median [IQR]	9	[4–18]	8	[3–16]	0.0030
History of a previous virologic failure, n (%)^a	104	(39.7)	194	(37.6)	0.569
CD4+ T cells at baseline/µL, median [IQR]	690	[470–944]	679	[466–949]	0.6147
CD4 < 350 cells/mL at baseline, n (%)	33	(12.6)	75	(14.3)	0.510
Cumulative Number of antiretroviral regimens before switch, median [IQR]	7	[5–9]	5	[3–7]	<0.001
Pre-switch therapy, n (%)
Mono-therapy	2	(0.8)	5	(0.9)	0.788
Dual-therapy	21	(8.0)	36	(6.9)	0.560
Three drug-regimens NNRTI-based	17	(6.5)	136	(25.6)	<0.001
Three drug-regimens PI-based	12	(4.5)	166	(31.7)	<0.001
Three drug-regimens INSTI-based	206	(78.6)	163	(31.1)	<0.001
Other	4	(1.5)	18	(3.4)	0.126
Switch from a previous INSTI regimen, n (%)	209	(79.8)	185	(35.3)	<0.001
Switch from a previous ABC regimen, n (%)	4	(1.5)	217	(41.4)	<0.001
M184V/I mutation, n (%)					0.020
Yes	12	(4.6)	40	(7.3)
No	182	(69.5)	277	(52.9)
Unknown	68	(25.9)	207	(39.5)
Follow-up
Discontinuation due to all cause	13	(5.0)	57	(10.9)	0.1970*
Discontinuation due to adverse events (grade 1–2)	7	(2.7)	48	(9.1)	0.0323*
Virologic failure	1	(0.4)	5	(0.9)	0.6276*
Discontinuation for toxicities
Gastrointestinal, n (%)	2	(0.7)	18	(3.4)	0.1160*
Neurological, n (%)	2	(0.7)	14	(2.7)	0.2398*
Bone, n (%)	0	(0)	1	(0.2)	–
Other, n (%)	2	(0.7)	13	(2.5)	0.2873*
Discontinuation for allergic reaction, n (%)	1	(0.4)	0	(0)	–
Self discontinuation, n (%)	0	(0)	2	(0.4)	–

ART, antiretroviral therapy; MSM, male who has sex with male; IVDU, intravenous drug users; ABC, abacavir; TDF/TAF, tenofovir disoproxil fumarato/tenofovir alafenamide; 3TC, lamivudine; PI, protease inhibitor; NNRTI, non-nucleoside reverse transcriptase inhibitor; INSTI, integrase strand transfer inhibitor.

^a It was defined as two consecutive HIV-RNA >50 copies/mL or one HIV-RNA >200 copies/mL in previously suppressed patients.

* p value for rate ratios with the Mantel–Haenszel method.

Table 2 Incidence rates (per 100-py) of virologic failure, discontinuation due to all causes and discontinuation due to treatment adverse events in HIV-1 infected patients, ART experienced with HIV-RNA level <50 copies/mL switching to BIC/TAF/FTC or to DTG/3TC/ABC in five centers in Italy

	Number of events	Person-years (×100)	Incidence rate within 3 months from the switch [95%CI]	RR	[95% CI]	p
BIC/TAF/FTC
Discontinuation due to all causes	13	0.8120	16.01	ref	–	–
			9.29–27.57
Discontinuation due to treatment adverse events	7	0.8120	8.62	ref	–	–
			4.10–18.08
Discontinuation due to virologic failure	1	0.8120	1.23	ref	–	–
			0.17–8.74
DTG/ABC/3TC
Discontinuation due to all causes	57	2.4010	23.74	1.48	0.81–2.71	0.1970
			8.31–30.77
Discontinuation due to treatment adverse events	48	2.4010	20.01	2.32	1.11–5.16	0.0323
			15.7–26.5
Discontinuation due to virologic failure	5	2.4010	2.08	1.69	0.19–14.56	0.6276
			0.87–5.00

TAF: Tenofovir alafenamide, DTG: dolutegravir, BIC: bictegravir, 3TC: lamivudine, FTC: emtricitabine.

Table 3 Multivariable cox model for discontinuation due to adverse events in HIV-1 infected, ART-experienced patients with HIV-RNA level <50 copies/mL switching to BIC/TAF/FTC or DTG/ABC/3TC in five centers in Italy

Variables	HR	95% CI	p
Group
BIC/TAF/FTC	–	–	–
DTG/3TC/ABC	3.28*	1.34–7.99	0.009
Gender
Male	–	–	–
Female	1.24	0.64–2.40	0.135
Transgender	4.80	0.57–40.1	0.147
Age at entry in years
<40 years	–	–	–
40–60 years	1.89	0.81–4.35	0.136
>60 years	2.85	1.08 − 7.53	0.034
Risk behavior
Heterosexual	–	–	–
MSM	0.67	0.31–1.44	0.306
IVDU	1.51	0.68–3.32	0.301
Other/unknown	1.12	0.44–2.87	0.798
Previous AIDS event
No	–	–	–
Yes	1.15	0.56–2.37	0.699
Years of antiretroviral treatment
>11 years	–	–	–
4–10 years	0.79	0.35–1.77	0.580
<3 years	1.87	0.75–4.62	0.173
CD4 baseline (cell/mm^3)
>350	–	–	–
<350	0.63	0.27–1.45	0.279
Pre-switch regimen containing abacavir
No	–	–	–
Yes	0.37	0.18–0.74	0.005
Pre-switch PI boosted regimen
No	–	–	–
Yes	1.10	0.62–1.96	0.736
Previous cardiovascular disease
No	–	–	–
Yes	0.46	0.16–1.28	0.138
Previous diabetes
No	–	–	–
Yes	2.42	0.52–11.2	0.257
Previous dyslipidemia
No	–	–	–
Yes	0.51	0.11–2.34	0.394
Previous neuropsychiatric illness
No	–	–	–
Yes	1.19	0.27–5.16	0.814
Number of previous ART regimens	1.01	0.90–1.13	0.771

ART, antiretroviral therapy; IVDU, intravenous drug users; TDF, tenofovir disoproxil fumarate; ABC, Abacavir; BIC, bictegravir; TAF, tenofovir alafenamide; 3TC, lamivudine; PI, protease inhibitor; NNRTI, non-nucleoside reverse transcriptase inhibitors; INSTI, integrase strand transfer inhibitor.