Efficacy, Durability, and Tolerability of Bictegravir/Emtricitabine/Tenofovir Alafenamide for the Treatment of HIV in a Real-world Setting in Belgium

Rakan Nasreddine; Eric Florence; Jean Cyr Yombi; Sophie Henrard; Gilles Darcis; Jens Van Praet; Linos Vandekerckhove; Sabine D. Allard; Rémy Demeester; Peter Messiaen; Nathalie Ausselet; Marc Delforge; Stéphane De Wit

Disclosures

HIV Medicine. 2023;24(8):914-924.

Abstract and Introduction

Abstract

Objectives: Our objective was to evaluate the efficacy, durability, and tolerability of bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) in a real-world setting in Belgium.

Methods: This was a retrospective, multicentre cohort study involving adult treatment-naïve (TN) and treatment-experienced (TE) people living with HIV receiving BIC/FTC/TAF between 1 January 2019 and 30 September 2020. The primary outcome was rate of virological suppression (plasma HIV-1 viral load <50 copies/mL; on-treatment analysis) at weeks 24 and 48. The main secondary outcomes included loss of virological suppression (LVS; two consecutive viral loads of >200 copies/mL after being virologically suppressed) by week 48 and analysis of resistance-associated mutations at time of LVS; tolerability of BIC/FTC/TAF over the 48-week study period; and change in weight and proportion of participants reporting a >10% weight gain at week 48.

Results: Overall, 2001 participants were included. Through 48 weeks, overall rate of virological suppression was 93.5%, with similar results observed in the following subgroups: age ≥50 years (92.7%), women (92.8%), Black sub-Saharan African (91%), TN (94%), TE (93.2%), and non-suppressed at baseline (86.6%). LVS was observed in 0.7% (n = 14) of participants, with one participant developing resistance-associated mutations to nucleoside reverse transcriptase inhibitors (184 V) and integrase strand transfer inhibitors (263KR). Of the 131 (6.5%) treatment discontinuations, the most common reason was an adverse event (2.4%), with the most frequent being central nervous system/psychiatric (0.4%) and gastrointestinal (0.4%) toxicity. Median weight gain at week 48 was 2 kg (interquartile range −1 to 5), and a >10% weight increase was observed in 11.6% of participants.

Conclusion: In this large real-world cohort, BIC/FTC/TAF showed excellent virological efficacy in a diverse population of patients with HIV. Rare occurrence of emergent drug resistance was observed, and treatment was well tolerated.

Introduction

Bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) is recommended by international guidelines as a first-line option for the treatment of most people living with HIV-1.^[1–4] Support for the use of BIC/FTC/TAF has come from several randomized clinical trials (RCTs) of treatment-naive^[5–9] and treatment-experienced people living with HIV.^[10–12] These trials showed that this regimen resulted in a rapid suppression of viraemia, was effective in maintaining virological suppression, was as tolerable as standard-of-care comparators, had a high genetic barrier to resistance, and had more favourable metabolic parameters. However, participants in RCTs are usually carefully selected, which can sometimes lead to certain groups being underrepresented. Furthermore, participants in the clinical trial setting tend to exhibit higher levels of treatment adherence than those in the real-world setting.^[13] Therefore, real-world studies provide complementary information to that obtained from RCTs and ensure that those results can be generalized to broader populations seen in daily clinical practice. The aim of this study was to describe the baseline characteristics of people living with HIV in Belgium receiving BIC/FTC/TAF and to evaluate its efficacy, durability, and tolerability in a real-world setting.

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Abstract and Introduction
Methodology
Results
Discussion
References

Table 1. Baseline characteristics of the study population.
Characteristic	Overall (N = 2001)
Age (years), n (%)
<50	1184 (59.2)
≥50	817 (40.8)
Sex, n (%)
Male	1299 (64.9)
Female	702 (35.1)
Ethnicity, n (%)
Caucasian	1145 (57.2)
Black sub-Saharan African	646 (32.3)
Other	146 (7.3)
Unknown	64 (3.2)
Weight (kg)
Median (IQR)	76 (67–87)
Data not available, n (%)	283 (14.1)
Co-morbidities, n (%)
Diabetes mellitus	76 (3.8)
Coronary heart disease	16 (0.8)
Non-AIDS-defining malignancy	68 (3.4)
Chronic renal disease	3 (0.1)
Data not available	470 (23.5)
Co-infections
HBV co-infection	93 (4.7)
HCV co-infection	82 (4.1)
Data not available	617 (30.8)
HIV acquisition, n (%)
MSM	884 (44.2)
Heterosexual	866 (43.3)
Other	80 (4)
Unknown	171 (8.5)
HIV treatment status, n (%)
Treatment-naïve	408 (20.4)
Treatment-experienced	1593 (79.6)
INSTI-experienced	1108 (55.4)
Prior AIDS defining illness, n (%)	510 (25.5)
Nadir CD4⁺ T-cell count (cells/μL)
Median (IQR)	308 (157–492)
Data not available, n (%)	51 (2.5)
Total time on ART prior to baseline (years)
Median (IQR)	6 (0.9–12.3)
Number of ART regimens prior to baseline
Median (IQR)	2 (1–4)
ARV resistance data available, n (%)	387 (19.3)
EFV resistance	53 (13.7)
3TC/FTC resistance	39 (10.1)
ABC resistance	37 (9.6)
RPV resistance	34 (8.8)
DRV resistance	24 (6.2)
TDF resistance	18 (4.7)
EVG/RAL resistance	9 (2.3)
Most common ART regimen prior to baseline, n (%)
EVG/c/FTC/TAF	399 (19.9)
DTG + FTC/TAF	241 (12)
EFV/FTC/TDF	92 (4.6)
DRV/c/FTC/TAF	80 (4)
DTG + FTC/TDF	59 (2.9)
HIV-1 viral load (copies/mL), n (%)
<50	1363 (68.1)
≥50	638 (31.9)
CD4⁺ T-cell count (cells/μL)
Median (IQR)	567 (367–793)
CD4⁺ T-cell count (cells/μL), n (%)
<350	418 (21)
350–499	327 (16.3)
≥500	1063 (53.1)
Data not available	193 (9.6)
CD4⁺/CD8⁺ ratio
Median (IQR)	0.7 (0.4–1.1)
Data not available, n (%)	741 (37)

Abbreviations: 3TC, lamivudine; ABC, abacavir; ART, antiretroviral therapy; ARV, antiretroviral; C, cobicistat; DRV, darunavir; DTG, dolutegravir; EFV, efavirenz; EVG, elvitegravir; FTC, emtricitabine; HBV, hepatitis B virus; HCV, hepatitis C virus; INSTI, integrase strand transfer inhibitor; IQR, interquartile range; MSM, men who have sex with men; RAL, raltegravir; RPV, rilpivirine; TAF, tenofovir alafenamide; TDF, tenofovir disoproxil fumarate.

Table 2. Rates of virological suppression for the overall study population and for various subgroups at weeks 24 and 48.
Characteristics	Week 24		Week 48
Characteristics	N	Rate of virological suppression (%)	N	Rate of virological suppression (%)
All participants	1611	92	1361	93.5
Age (years)
<50	939	91.7	785	94
≥50	672	92.6	576	92.7
Sex
Male	1061	91.6	885	93.8
Female	550	92.9	476	92.8
MSM	725	94.3	624	94.7
Black sub-Saharan African	496	89.5	411	90.8
HIV treatment status
Naïve	363	87.5	300	94
Experienced	1248	93.4	1061	93.2
INSTI-experienced	918	93.8	734	93.9
Total time on ART prior to baseline (years)
≤6	1091	91.4	913	93.5
>6	520	93.5	448	93.3
Number of ART regimens prior to baseline
≤2	693	91.6	566	93.9
>2	918	93.3	795	93.3
Baseline resistance
EFV resistance	39	94.9	39	89.7
3TC/FTC resistance	33	84.8	30	83.3
ABC resistance	30	90	22	86.4
RPV resistance	32	87.5	26	88.5
DRV resistance	32	96.6	25	88
TDF resistance	17	94.1	14	78.6
EVG/RAL resistance	6	83.3	3	66.7
ART regimen prior to baseline
ABC-containing	195	92.8	153	92.2
TDF-containing	249	88.8	229	91.7
TAF-containing	791	94.6	638	94.5
RPV-containing	63	93.7	60	92.8
EFV-containing	92	89.1	74	89.2
DTG-containing	431	92.6	358	93.6
Baseline HIV-1 viral load (copies/mL)
<50	1098	97.2	921	96.7
≥50	513	81.1	440	86.6
Baseline CD4⁺ T-cell count (cells/μL)
<350	379	81.5	308	86.8
350–499	264	93.6	222	94.6
≥500	968	95.3	831	95.7

Abbreviations: 3TC, lamivudine; ABC, abacavir; ART, antiretroviral therapy; DRV, darunavir; DTG, dolutegravir; EFV, efavirenz; EVG, elvitegravir; FTC, emtricitabine; INSTI, integrase strand transfer inhibitor; MSM, men who have sex with men; N, number of participants on treatment, in follow-up, and with available data; RAL, raltegravir; RPV, rilpivirine; TAF, tenofovir alafenamide; TDF, tenofovir disoproxil fumarate.

Table 3. Change in weight at week 48, along with the proportion of patients experiencing 5%–10% and >10% increase in weight from baseline for the study cohort and for various sub-groups.
Characteristics	N	Median change in weight (kg) from baseline (IQR)	5%–10% increase in weight from baseline (%)	>10% increase in weight from baseline (%)
All patients	741	2 (−1–5)	19.2	11.6
Age (years)
<50	435	2 (0–5)	20	13.6
≥50	306	1 (−1–4)	18	8.8
Sex
Male	487	1 (−1–3)	17.9	12.2
Female	254	2 (0–5)	21.2	10.6
MSM	334	1 (−1–5)	20.1	8.7
Black sub-Saharan African	250	2 (0–5)	19.6	12
HIV treatment status at baseline
Naïve	160	3 (0–8)	21.3	25.6
Experienced	581	1 (−1–4)	17.8	7.6
INSTI-experienced	412	1 (−1–4)	17.4	7.2
Total time on ART prior to baseline (years)
≤6	475	2 (0–5)	19.6	11.5
>6	266	1 (−1–4)	18.4	10.9
Number of ART regimens prior to baseline
≤2	299	2 (1–5)	20.2	13.8
>2	442	1 (0–4)	18	9.9
ART regimen prior to baseline
ABC-containing	90	2 (0–4)	16.7	8.9
TDF-containing	96	3 (0–7)	29.7	20.8
TAF-containing	376	1 (−1–3)	16.2	4
RPV-containing	23	1 (−2–2)	19.4	11.9
EFV-containing	36	3 (0–7)	21.9	13.6
DTG-containing	197	1 (−1–4)	16.8	9.6
Baseline HIV-1 VL (copies/mL)
<50	511	1 (−1–4)	17.6	6.5
≥50	230	4 (1–8)	22.6	23
Baseline CD4⁺ T-cell count (cells/μL)
<350	215	4 (1–9)	26.1	24.8
350–499	126	2 (0–5)	24.6	7.1
≥500	400	1 (−1–3)	13.2	7.6

Abbreviations: ABC, abacavir; ART, antiretroviral therapy; DTG, dolutegravir; EFV, efavirenz; INSTI, integrase strand transfer inhibitor; IQR, interquartile range; MSM, men who have sex with men; N, number of participants on treatment, in follow-up, and with available data; RPV, rilpivirine; TAF, tenofovir alafenamide; TDF, tenofovir disoproxil fumarate; VL, viral load.