Effectiveness of Bictegravir/Emtricitabine/Tenofovir Alafenamide in Virologically Suppressed People with HIV on Any Antiretroviral Therapy Regimen: The Retrospective ESSENTIAL Study

Abstract

Introduction

Real-world evidence on the effectiveness and durability of bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) as a switch strategy in virologically suppressed people with HIV (PWH) is important for clinical decision-making, particularly in ageing populations with multiple comorbidities and concomitant medications and in individuals previously treated with rilpivirine.

Methods

ESSENTIAL (GS-IT-380–7059) is a retrospective, single-centre observational study including adults with HIV-RNA < 50 copies/ml who switched to BIC/FTC/TAF between July 2019 and April 2024 at ASST Fatebenefratelli Sacco, Milan, Italy. The primary endpoint was the virological suppression rate (HIV-RNA < 50 copies/ml) evaluated at 6 and 12 months after switching to BIC/FTC/TAF (observed-case analysis of available data). Secondary endpoints included treatment durability (Kaplan-Meier estimates of time to treatment interruption for any cause) and safety. A prespecified subgroup analysis evaluated individuals switching from rilpivirine/emtricitabine/tenofovir alafenamide (RPV/FTC/TAF).

Results

Overall, 799 individuals were included (median age 53 [IQR 45, 58] years; 83% male). The cohort reflected substantial clinical complexity: 82.6% had ≥ 1 comorbidity (predominantly metabolic) and 34.2% were taking ≥ 3 concomitant medications; potential drug-drug interactions with the pre-switch antiretroviral regimen were identified in approximately 14% of cases. After the switch, virological suppression was maintained in 97.4% of participants at 6 months and 98% at 12 months. In the subgroup switching from RPV/FTC/TAF (n = 103), virological suppression rates were 93.9% at 6 months and 98% at 12 months, with only two confirmed virological failures. Kaplan-Meier analysis showed high treatment durability with few discontinuations, most of which were unrelated to virological failure or adverse events. Adverse events were infrequent (0.8% at 6 months; 0.3% at 12 months), with no unexpected safety signals during follow-up.

Conclusion

In this large real-world cohort of virologically suppressed individuals, characterized by ageing, high comorbidity burden, and frequent concomitant medication use, switching to BIC/FTC/TAF was associated with sustained virological control and good tolerability over 12 months, including among those transitioning from RPV-based regimens. These findings provide additional real-world evidence supporting BIC/FTC/TAF as a durable and well-tolerated switch strategy in routine clinical practice.

Supplementary Information

The online version contains supplementary material available at 10.1007/s40121-026-01408-2.

Plain Language Summary

People living with HIV may need to change treatment over time because of side effects, drug interactions, medical conditions, or the need for a simpler regimen. In this study, we evaluated people living with HIV whose virus was already well controlled and who changed treatment to a single-tablet regimen containing bictegravir, emtricitabine, and tenofovir alafenamide during routine clinical care at a hospital in Milan, Italy. The study included 799 adults, many of whom were older, had other medical conditions, and were taking additional medications. Most participants maintained viral control after changing treatment. At 12 months, 98% of participants with available data still had undetectable levels of HIV in their blood. The treatment was generally well tolerated, with few adverse events and few treatment interruptions related to safety. Body mass index did not show a clinically relevant change during follow-up, although data were not available for all participants. We also evaluated people who switched from a rilpivirine-based regimen, and their outcomes were similar. These findings support the use of bictegravir, emtricitabine, and tenofovir alafenamide as a treatment-switch option in routine clinical practice, including for people with other medical conditions or multiple medications.

Supplementary Information

The online version contains supplementary material available at 10.1007/s40121-026-01408-2.

Key Summary Points

Why carry out this study?

People with HIV are ageing and frequently have comorbidities and concomitant medications, making regimen simplicity, tolerability, and low potential for drug-drug interactions important in long-term care.

Real-world data on switching to bictegravir/emtricitabine/tenofovir alafenamide, including from rilpivirine-based regimens, remain useful to complement clinical trial evidence.

This study assessed virological outcomes, treatment durability, safety, and body mass index changes after switching to bictegravir/emtricitabine/tenofovir alafenamide in virologically suppressed people with HIV.

What was learned from this study?

Among 799 virologically suppressed people with HIV, switching to bictegravir/emtricitabine/tenofovir alafenamide maintained virological suppression in 97.4% of participants at 6 months and 98.0% at 12 months among those with available data.

Treatment persistence was high and adverse events were uncommon over 12 months.

Outcomes were similar among individuals switching from rilpivirine/emtricitabine/tenofovir alafenamide, supporting this regimen as a treatment-switch option in routine clinical practice.

No clinically relevant changes in body mass index were observed during follow-up; however, these findings should be interpreted with caution given the proportion of missing data.

Introduction

The fixed-dose combination of bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) is currently recommended by major international guidelines both for antiretroviral therapy (ART) initiation and as a switch option in virologically suppressed people with HIV.(PWH) [1, 3]. BIC is an integrase strand transfer inhibitor (INSTI) with a high genetic barrier to resistance, a favourable tolerability profile, and low potential for drug-drug interactions, making it a suitable option for long-term HIV management [4, 5].

Randomised clinical trials have shown that switching to BIC/FTC/TAF maintains virological suppression and is associated with a favourable safety profile, including among individuals switching from non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimens such as rilpivirine (RPV) ^6,9. Real-world data are essential to confirm these findings in routine clinical practice and across more heterogeneous populations.

Although real-world studies have confirmed the effectiveness and durability of BIC/FTC/TAF in routine clinical practice, data specifically addressing outcomes after switching from RPV-containing regimens remain limited ^7,10. This is clinically relevant, as RPV-based regimens are commonly prescribed in virologically suppressed individuals because of their tolerability and convenience. However, switching to an INSTI-based regimen such as BIC/FTC/TAF may provide advantages in terms of higher genetic barrier, reduced potential for drug-drug interactions, and the absence of food requirements.

The present study was designed to evaluate the effectiveness, treatment durability, and safety of switching to BIC/FTC/TAF in a real-world cohort of virologically suppressed individuals, with a specific focus on those previously treated with rilpivirine/emtricitabine/tenofovir alafenamide (RPV/FTC/TAF).

Methods

Study Design and Participants

The ESSENTIAL study (GS-IT-380–7059) is a retrospective observational cohort study conducted at the Infectious Diseases Department of ASST Fatebenefratelli Sacco, Milan, Italy. All patients living with HIV (PLWH) who switched to BIC/FTC/TAF while virologically suppressed were eligible for inclusion. Virological suppression was defined as an HIV-RNA level < 50 copies/ml at the time of the switch. Participants were identified through electronic medical records, and follow-up data were collected for a minimum of 6 months and up to 12 months after switching to BIC/FTC/TAF. A prespecified subgroup analysis was conducted among individuals switching from RPV/FTC/TAF.

Follow-up data were collected during routine clinical care. At our centre, virological and laboratory assessments are generally performed every 6 months in clinically stable virologically suppressed individuals, with additional visits scheduled when clinically indicated.

Data Collection and Variables

Baseline demographic and clinical characteristics were collected at the time of switch, including age, sex assigned at birth, gender, mode of HIV acquisition, comorbidities, prior antiretroviral exposure, CD4 cell count, and selected laboratory parameters collected as part of routine clinical care. Treatment-emergent adverse events, reasons for treatment discontinuation, and the timing of any regimen modification were also recorded.

Adverse events were defined as any new symptom, laboratory abnormality, or clinical event documented by the treating physician after switch and considered potentially related to bictegravir/emtricitabine/tenofovir alafenamide.

Potential drug-drug interactions were classified according to the University of Liverpool HIV Drug Interactions database. “Yellow” classification indicates a potential weak interaction or need for monitoring; “orange” indicates a potential clinically relevant interaction that may require dose adjustment, monitoring, or treatment modification; “red” indicates a contraindicated or not recommended combination.

Statistical Analysis

Continuous variables were summarised as medians with interquartile ranges, and categorical variables as frequencies and percentages. Comparisons between groups were performed using non-parametric tests for continuous variables and the chi-square or Fisher’s exact test for categorical variables, as appropriate.

The primary endpoint was the virological suppression rate (HIV-RNA < 50 copies/ml) evaluated at 6 and 12 months after switching to BIC/FTC/TAF (observed-case analysis). Secondary endpoints included changes in CD4 cell count, the cumulative incidence of virological failure, adverse events, and overall treatment durability.

Treatment durability was assessed using Kaplan-Meier survival analyses to estimate the time to discontinuation of BIC/FTC/TAF for any cause. Time was calculated from the date of switch until treatment discontinuation or censoring at the last available clinical follow-up visit. Differences between survival curves were evaluated using the log-rank test. The cumulative incidence of virological failure was estimated, with confirmed virological rebound (defined as two consecutive HIV RNA values > 200 copies/ml or a single HIV RNA value > 200 copies/ml followed by treatment modification according to the treating physician’s judgement) as the event of interest. The primary analysis was conducted as an observed-case analysis including participants with available HIV RNA measurements at each time point. Participants without available 6- or 12-month data were excluded from the corresponding observed-case denominator.

Differences in CD4 cell counts across baseline, 6 months, and 12 months were assessed using the Friedman test, followed by pairwise comparisons adjusted for multiple testing.

Body mass index was collected at baseline and 12 months when available. Changes in CD4 cell count and body mass index from baseline were assessed using paired analyses among participants with available measurements at both time points.

A two-sided p-value < 0.05 was considered statistically significant. Statistical analyses were performed using standard statistical software.

Ethical Approval

The study was conducted in accordance with the principles of the Declaration of Helsinki and was approved by the local Ethics Committee (protocol no. CET 256–2024). Given the retrospective design and the use of anonymised data, the requirement for informed consent was waived. Patient consent was waived because of the retrospective nature of the study and anonymised data collection.

Results

A total of 799 individuals who switched to BIC/FTC/TAF were included in the analysis. Baseline characteristics of the overall population and of the subgroup switching from RPV/FTC/TAF (n = 103) are summarised in Tables 1 and 2, respectively. The median age was 53 (IQR 45, 58) years, and most participants were male (83%). Most individuals acquired HIV through sexual exposure (heterosexual 42.2% and men who have sex with men 31.7%). Comorbidities were common, including dyslipidaemia (38.7%) and hypertension (24.9%), and nearly half of the cohort was overweight or obese. Polypharmacy was frequently observed at baseline, with approximately 14% of participants receiving concomitant medications classified as “orange” or “red” according to the Liverpool drug-drug interaction database in relation to their pre-switch antiretroviral regimen.

Table 1.

Baseline characteristics of the overall study population

	Overall n = 799
Gender, n (%)
Female cisgender	204 (25.5)
Male cisgender	571 (71.5)
TGW	24 (3.0)
Age, median [IQR]	53 [45, 58]
Italian born, n (%)	632 (79.5)
Mode of HIV acquisition, n (%)
HE	337 (42.2)
PWID	146 (18.3)
MSM	253 (31.7)
Other/unknown	56 (7.0)
Transfusions	7 (0.9)
Previous AIDS, n (%)	309 (39.1)
CD4 cell/mm3, median [IQR]	701 [502, 903]
CD8 cell/mm3, median [IQR] n = 122	766 [544, 1070]
Duration of previous treatment [months], median [IQR]	33 [24, 53]
Previous therapeutic lines, median [IQR]	4 [2, 7]
Previous virological failure to INSTIs, n (%)	13 (1.6)
Archived M184V, n (%)	100 (24.8)
Archived K65R, n (%)	2 (0.5)
Comorbidities, n (%)
Without any comorbidity	139 (17.4)
Hypertension	209 (26.2)
Diabetes	64 (8.0)
ASCVD	76 (9.5)
BMI > 30	23 (2.9)
BMI kg/m2, median (n/N) [IQR]	24.9 (437/799) [22.9, 27.4]
Dyslipidemia	306 (38.3)
CKD (ClCr < 30 ml/min)	16 (2.0)
Lung disease	42 (5.3)
Solid neoplasm	49 (6.1)
Haematological neoplasm	12 (1.5)
AIDS defining cancer	4 (0.5)
Sexually transmitted infections	87 (10.9)
Previous HBV	144 (18.0)
Chronic HBV	40 (5.0)
Previous HCV	168 (21.0)
Chronic HCV	7 (0.9)
Chronic HDV	2 (0.3)
Cirrhosis	21 (2.6)
Psychiatric disorder	98 (12.3)
Bone disease	145 (18.1)
Neurodegenerative disease	8 (1.0)
Autoimmune disorders	26 (3.3)
Other comorbidities	203 (25.4)
Concomitant medication, n (%)
None	187 (23.4)
Antihypertensive	215 (26.9)
Antiplatelet	101 (12.6)
Anticoagulant	9 (1.1)
Statin	206 (25.8)
Ezetimibe	40 (5.0)
Fibrate	16 (2.0)
Other lipid-lowering agents	22 (2.8)
Chemotherapy	0 (0.0)
Inhalatory lung	13 (1.6)
Proton pump inhibitors	96 (12.0)
Oral antidiabetic	51 (6.4)
Insulin	16 (2.0)
DDAs for hepatitis C	2 (0.3)
Antidepressant	35 (4.4)
Antipsychotic	26 (3.3)
Benzodiazepine	66 (8.3)
Methadone	13 (1.6)
Other drugs active against CNS	34 (4.3)
Bone drugs	9 (1.1)
Immunosuppressants	17 (2.1)
Magnesium	0 (0.0)
Calcium supplements	71 (8.9)
Other supplements	220 (27.5)
Other medications	287 (35.9)
Interactions according to the Liverpool Database, n (%)
Yellow	8 (1.0)
Orange	64 (8.0)
Red	3 (0.4)
Polypharmacy
≥ 3 concomitant medications	34.2%
≥ 5 concomitant medications	14%

Baseline demographic and clinical characteristics of people with HIV included in the ESSENTIAL study at the time of switch to bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF). Data are presented as median (interquartile range) or number (percentage), as appropriate

IQR interquartile range; TGW transgender women; HE heterosexual contact; PWID people who inject drugs; MSM men who have sex with men; INSTIs integrase strand transfer inhibitors; ASCVD atherosclerotic cardiovascular disease; BMI body mass index; CKD chronic kidney disease; ClCr creatinine clearance; HBV hepatitis B virus; HCV hepatitis C virus; HDV hepatitis D virus; CNS central nervous system; DAAs direct-acting antivirals

Table 2.

Baseline characteristics of individuals switching from RPV/FTC/TAF

	Overall n = 103
Gender, n (%)
Cisgender female PWH	25 (24.3)
Cisgender male PWH	72 (69.9)
TGW PWH	6 (5.8)
Age, median [IQR]	50 [43, 57]
Italian born, n (%)	81 (78.6)
Mode of HIV acquisition, n (%)
HE	37 (35.9)
PWID	13 (12.6)
MSM	39 (37.9)
Other/unknown	13 (12.6)
Transfusions	1 (1.0)
Previous AIDS, n (%)	28 (28.3)
CD4 cell/mm3, median [IQR]	730 [548, 911]
CD8 cell/mm3, median [IQR] n = 6	634 [457, 878]
Duration of previous treatment [months], median [IQR]	27 [17, 45]
Previous therapeutic lines, median [IQR]	4 [3, 5]
Previous virological failure to INSTIs, n (%)	1 (1)
Archived M184V, n (%)	4 (8.5)
Archived K65R, n (%)	1 (2.1)
Comorbidities, n (%)
Without any comorbidity	12 (11.7)
Hypertension	23 (22.3)
Diabetes	11 (10.7)
ASCVD	11 (10.7)
BMI > 30	6 (5.8)
Dyslipidemia	41 (39.8)
CKD (ClCr < 30 ml/min)	2 (1.9)
Lung disease	8 (7.8)
Solid neoplasm	6 (5.8)
Haematological neoplasm	1 (1.0)
AIDS defining cancer	2 (1.9)
Sexually transmitted infections	34 (33.0)
Previous HBV	19 (18.4)
Chronic HBV	5 (4.9)
Previous HCV	14 (13.6)
Chronic HCV	1 (1.0)
Chronic HDV	0 (0.0)
Cirrhosis	2 (1.9)
Psychiatric disorder	17 (16.5)
Bone disease	14 (13.6)
Neurodegenerative disease	3 (2.9)
Autoimmune disorders	7 (6.8)
Other comorbidities	15 (14.6)
Concomitant medication, n (%)
None	23 (22.3)
Antihypertensive	25 (24.3)
Antiplatelet	10 (9.7)
Anticoagulant	0 (0.0)
Statin	28 (27.2)
Ezetimibe	2 (1.9)
Fibrate	1 (1.0)
Other lipid-lowering agents	0 (0.0)
Chemotherapy	0 (0.0)
Inhalatory lung	2 (1.9)
Proton pump inhibitors	15 (14.6)
Oral antidiabetic	10 (9.7)
Insulin	2 (1.9)
DDAs for hepatitis C	0 (0.0)
Antidepressant	7 (6.8)
Antipsychotic	4 (3.9)
Benzodiazepine	13 (12.6)
Methadone	1 (1.0)
Other drugs active against CNS	2 (1.9)
Bone drugs	1 (1.0)
Immunosuppressants	5 (4.9)
Magnesium	0 (0.0)
Calcium supplements	2 (1.9)
Other supplements	36 (35.0)
Other medications	39 (37.9)
Interactions according to Liverpool Database, n (%)
Yellow	1 (1.0)
Orange	12 (11.7)
Red	0 (0.0)

Baseline demographic and clinical characteristics of the subgroup of people with HIV switching from rilpivirine/emtricitabine/tenofovir alafenamide (RPV/FTC/TAF) to bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF). Data are presented as median (interquartile range) or number (percentage), as appropriate

IQR interquartile range; TGW transgender women; HE heterosexual contact; PWID people who inject drugs; MSM men who have sex with men; INSTIs integrase strand transfer inhibitors; ASCVD atherosclerotic cardiovascular disease; BMI body mass index; CKD chronic kidney disease; ClCr creatinine clearance; HBV hepatitis B virus; HCV hepatitis C virus; HDV hepatitis D virus; CNS central nervous system; DAAs direct-acting antivirals

At the time of switch, the median CD4 cell count was 701 cells/mm³ (IQR 502–903) in the overall cohort and 730 cells/mm³ (IQR 548–911) in the subgroup of individuals switching from RPV/FTC/TAF, with comparable immunological profiles between groups.

Reasons for switching to BIC/FTC/TAF are summarized in Fig. 1. The most common reasons for switching to BIC/FTC/TAF were the need to increase the genetic barrier of the regimen, reported in 489 individuals (61.2%), and treatment simplification, reported in 209 individuals (26.2%). Other reasons included potential or documented drug-drug interactions in 34 individuals (4.3%) and other clinical reasons in 48 individuals (6.0%). Less frequent reasons included central nervous system toxicity, dyslipidaemia, gastrointestinal toxicity, hepatic or renal toxicity, patient choice, osteoporosis, lipodystrophy, and adherence-related considerations. Reasons for switching were recorded as a single primary reason per participant.

Fig. 1.

Reasons for switching to BIC/FTC/TAF. Bar chart showing the number of participants by reason for switching to bictegravir/emtricitabine/tenofovir alafenamide in the overall study population (N = 799). Reasons were recorded as a single primary reason per participant. CNS, central nervous system; BIC/FTC/TAF: bictegravir/emtricitabine/tenofovir alafenamide

Virological Outcomes

Virological suppression was maintained in the majority of participants throughout the follow-up period. At 6 months, 746 of 766 individuals (97.4%; 95% CI 96.3–98.5%) had HIV-RNA < 50 copies/ml, and at 12 months, 728 of 743 (98.0%; 95% CI 97.0–99.0%) were virologically suppressed (observed-case analysis). In the prespecified subgroup switching from RPV/FTC/TAF, virological suppression was 93.9% at 6 months and 98% at 12 months.

Virological events were uncommon. The cumulative incidence of virological failure was 0.5% (95% CI 0.2–1.3%) at 6 months and 1.5% (95% CI 0.8–2.6%) at 12 months. Episodes of detectable HIV-RNA were infrequent and mostly consisted of transient low-level viraemia, generally occurring in the context of documented suboptimal adherence. In most cases, these episodes did not lead to treatment discontinuation or modification, and virological suppression was subsequently re-established. Only one participant discontinued BIC/FTC/TAF because of virological failure.

In individuals switching from RPV/FTC/TAF, the cumulative incidence of virological failure was 0% at 6 months and 2.1% (95% CI 0.5–8.3%) at 12 months, with only two confirmed virological failures.

Treatment Durability

Treatment persistence with BIC/FTC/TAF was high, as shown by the Kaplan-Meier analysis (Fig. 2). Detailed Kaplan-Meier estimates for the overall cohort and subgroup analyses according to age and baseline antiretroviral regimen are reported in Supplementary Table S1. The estimated probability of remaining on treatment without discontinuation for any cause was 96.6% (95% CI 95.3–97.9) at 6 months and 94.6% (95% CI 93.0–96.2) at 12 months. Treatment persistence remained consistently high across age subgroups at the time of switch, with no clinically meaningful differences observed (Fig. 2B). When stratified by age, treatment persistence was 99.1% (95% CI 97.5–100) at 6 months and 98.1% (95% CI 95.4–100) at 12 months among individuals aged < 40 years; 96.4% (95% CI 94.9–98.0) and 94.4% (95% CI 92.4–96.4), respectively, among those aged 40–60 years; and 95.1% (95% CI 91.6–98.6) and 92.6% (95% CI 88.1–97.1), respectively, among those aged > 60 years. Differences across age groups were not statistically significant by log-rank test (p = 0.310). In analyses stratified by prior regimen, treatment persistence remained high. In the subgroup switching from RPV/FTC/TAF, treatment persistence was 97.1% (95% CI 93.8–100) at both 6 and 12 months, compared with 96.5% (95% CI 95.2–97.9) and 94.3% (95% CI 92.5–96.0) among individuals switching from other regimens, with no clinically meaningful differences between groups (Fig. 2C). Differences between groups were not statistically significant by log-rank test (p = 0.384).

Fig. 2.

Treatment durability of BIC/FTC/TAF. Kaplan-Meier estimates of the probability of remaining on bictegravir/emtricitabine/tenofovir alafenamide without treatment interruption for any cause. A Overall cohort, with 95% confidence intervals. B Estimates stratified by age group: < 40 years, 40–60 years, and > 60 years. C Estimates according to prior antiretroviral regimen: rilpivirine/emtricitabine/tenofovir alafenamide versus other antiretroviral regimens. Participants without treatment interruption were censored at the last available follow-up. ART antiretroviral therapy; CI confidence interval; RPV/FTC/TAF rilpivirine/emtricitabine/tenofovir alafenamide, BIC/FTC/TAF bictegravir/emtricitabine/tenofovir alafenamide

Treatment interruptions were uncommon and occurred for heterogeneous reasons (Fig. 3). Missing virological assessments during follow-up were mainly attributable to loss to follow-up (n = 8) and transfer of care to another clinical centre (n = 3) rather than documented virological failure. During the first 6 months after switch, the most frequently reported reasons were dropout (n = 7), dyslipidaemia (n = 5), simplification (n = 5), central nervous system toxicity (n = 4), and other reasons (n = 4). No treatment interruption due to virological failure was reported during the first 6 months. Between 6 and 12 months, the most frequently reported reasons were simplification (n = 6), hepatic or renal toxicity (n = 3), pregnancy (n = 3), dropout (n = 3), death (n = 2), and weight gain (n = 2). One treatment interruption due to virological failure was reported between 6 and 12 months.

Fig. 3.

Reasons for treatment interruption. Bar chart showing the number of participants who interrupted treatment for each reason during follow-up, stratified by time interval after switching to bictegravir/emtricitabine/tenofovir alafenamide. A total of 33 and 23 participants interrupted treatment during months 0–6 and 6–12, respectively. Reasons were recorded as a single primary reason per participant. CNS central nervous system

Immunological and Laboratory Parameters

CD4 cell counts showed a modest increase during follow-up, without clinically meaningful changes in immunological status. In the overall cohort, the median CD4 count was 701 cells/mm³ (IQR 502–903) at baseline, 704 cells/mm³ (IQR 518–899) at 6 months, and 732 cells/mm³ (IQR 531–935) at 12 months. Although paired analyses identified statistically significant differences over time (median CD4 count was 701 [503–903] cells/mm³ at baseline, 704 [518–899] cells/mm³ at Month 6 and 732 [531–935] cells/mm³ at Month 12; p < 0.035 and p < 0.0001 respectively), the absolute magnitude of change was small and not considered clinically meaningful. Similar trends were observed in individuals switching from RPV/FTC/TAF, with median CD4 cell counts of 730 cells/mm³ (IQR 548–911) at baseline, 722 cells/mm³ (IQR 576–896) at 6 months, and 746 cells/mm³ (IQR 569–951) at 12 months. Laboratory parameters assessed during routine clinical care showed no clinically relevant variations over time and did not lead to treatment modification.

Safety

BIC/FTC/TAF was generally well tolerated. In the overall cohort, adverse events were reported in 6 individuals (0.8%) at 6 months and in 2 individuals (0.3%) at 12 months. Discontinuations due to adverse events were rare, and no unexpected safety signals emerged during the observation period.

Body mass index data were available for 437/799 participants at baseline and 433/743 at 12 months. Median body mass index was 24.9 kg/m² (IQR 22.9–27.4) at baseline and 25.0 kg/m² (IQR 22.8–27.5) at 12 months. In paired analyses, the median change from baseline to month 12 was 0.0 kg/m² (IQR – 0.4–0.7), indicating no clinically relevant variation in body mass index over follow-up. Weight gain was reported as the reason for treatment discontinuation in two participants between Month 6 and Month 12.

Discussion

In this large real-world cohort of virologically suppressed individuals, characterised by a median age of 53 years, a high prevalence of comorbidities, and frequent concomitant medication use, switching to BIC/FTC/TAF was associated with sustained virological control and high treatment persistence over 12 months. Virological suppression rates of 97.4% at 6 months and 98% at 12 months are consistent with findings from randomised clinical trials and previous observational studies supporting BIC/FTC/TAF as an effective switch strategy in routine clinical practice [6, 8.

The demographic and clinical characteristics of our cohort reflect the evolving demographic profile of PWH in a high-income-country setting, characterised by ageing, a high burden of comorbidities, frequent polypharmacy, and prolonged exposure to antiretroviral therapy. In this context, switching to BIC/FTC/TAF was primarily driven by the need to increase regimen robustness (higher genetic barrier) and to simplify therapy, in line with routine clinical decision-making in populations with comorbidities and polypharmacy. Selecting regimens with a low potential drug-drug interaction combined with a high genetic barrier of the regimen and avoidance of food requirements is clinically relevant. Notably, a proportion of participants were receiving concomitant medications classified as “orange” or “red” according to the Liverpool database in relation to their pre-switch regimen, supporting the switch to BIC/FTC/TAF as an appropriate strategy to minimize the risk of drug-drug interactions in this setting.

BIC/FTC/TAF demonstrated high treatment persistence with a low rate of treatment discontinuation and a low proportion of virological events throughout follow-up. Early discontinuations were uncommon and were rarely related to virological failure or safety concerns, reinforcing the favourable tolerability profile of BIC/FTC/TAF. This pattern mirrors durability trends previously described in clinical trials and recent real-world cohorts [4, 5, 10].

Individuals switching from RPV/FTC/TAF showed outcomes comparable to those of the overall cohort, maintaining high rates of virological suppression and stable immunological profiles. These findings are particularly relevant given the widespread use of RPV-based regimens as long-term treatment options in virologically suppressed individuals. Switching to an INSTI-based regimen with a higher genetic barrier to resistance may provide an added margin of robustness in patients with adherence challenges or evolving clinical complexity [6, 9].

Immunological parameters were maintained during follow-up, with only modest changes in CD4 cell counts that were not considered clinically meaningful. These observations are consistent with previous reports describing the favourable safety and tolerability profile of BIC/FTC/TAF in both clinical trials and real-world settings [7]. Weight gain has been reported following initiation or switching to integrase strand transfer inhibitor-based regimens and may be of particular clinical relevance in people with HIV with metabolic comorbidities. Previous studies have suggested that weight increases may be more pronounced among individuals switching from tenofovir dysoproxil- or efavirenz-based regimens [11, 12]. In the present study, no clinically relevant change in body mass index was observed after switching to bictegravir/emtricitabine/tenofovir alafenamide, including among individuals switching from rilpivirine/emtricitabine/tenofovir alafenamide. However, body mass index data were not systematically available for all participants because of the retrospective design; therefore, these findings should be interpreted with caution.

This study has several limitations. Its retrospective, single-centre observational design may have introduced selection bias and unmeasured confounding. The analysis was based on available clinical data, and missing information at 6 and 12 months may have affected observed-case estimates of virological suppression, body mass index, laboratory parameters, and adverse events. Body mass index was not systematically recorded for all participants, resulting in a substantial proportion of missing data and limiting the interpretation of weight-related outcomes. Resistance data were not available for all individuals, and the low number of virological failures limited the ability to identify predictors of viraemia or treatment interruption. Finally, adverse events were identified from routine clinical documentation and may have been underreported.

Nevertheless, the large sample size, the inclusion of a clinically relevant subgroup of individuals switching from RPV/FTC/TAF, and the consistency of outcomes across clinically relevant subgroups strengthen the reliability and generalisability of our findings.

Conclusions

In this large real-world cohort, of virologically suppressed PWH, characterised by ageing, high comorbidity burden, and frequent concomitant medication use, switching to BIC/FTC/TAF maintained high rates of virological suppression and was associated with favorable treatment persistence over 12 months. Outcomes were consistent across clinically relevant subgroups, including individuals transitioning from RPV/FTC/TAF.

These findings provide additional real-world evidence supporting the role of BIC/FTC/TAF as a switch strategy in routine clinical practice, particularly in ageing and comorbid populations where regimen simplicity and minimization of drug-drug interaction risk are key considerations.

Supplementary Information

Below is the link to the electronic supplementary material.

Author Contributions

Maria Vittoria Cossu, Davide Moschese, Andrea Giacomelli, Laura Albini, Gabriele Forcina and Andrea Gori contributed to study conception and design. Maria Vittoria Cossu, Davide Moschese, Maddalena Matone, Letizia Oreni, Giorgia Carrozzo, Andrea Poloni, Giacomo Pozza, Cristina Gervasoni, Agostino Riva, and Andrea Giacomelli contributed to data collection and interpretation. Statistical analyses were performed by Letizia Oreni. The first draft of the manuscript was written by Maria Vittoria Cossu. All authors critically revised the manuscript, approved the final version, and agree to be accountable for all aspects of the work. All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published.

Funding

Sponsorship for this study and the Rapid Service Fee were funded by Gilead Sciences.

Data Availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Declarations

Conflict of Interest

Maria Vittoria Cossu reports payment or honoraria for lectures, presentations, or education events from Gilead and ViiV; Davide Moschese reports payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing, or education events from Gilead and ViiV; Cristina Gervasoni reports personal fees from MSD, ViiV, Gilead, and Janssen-Cilag; Agostino Riva reports payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing, or education events from Gilead and ViiV; Andrea Giacomelli reports consulting fees from Mylan and Janssen-Cilag; payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing, or educational events from Gilead and ViiV; payment for expert testimony from Jansen; support for attending meetings and/or travel from Gilead, ViiV, and MSD; Andrea Gori reports grants or contracts from ViiV, Bristol Myers Squibb, and Gilead; consulting fees from ViiV, Gilead, Janssen-Cilag, Merck Sharp & Dohme, Bristol-Myers Squibb, Pfizer, and Novartis; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from ViiV, Gilead, Janssen-Cilag, Merck Sharp & Dohme, Bristol Myers Squibb, Pfizer, and Novartis; support for attending meetings and/or travel from ViiV, Gilead, Janssen-Cilag, Merck Sharp & Dohme, Bristol-Myers Squibb, Pfizer, and Novartis. Maddalena Matone, Letizia Oreni, Giorgia Carrozzo, Andrea Poloni, and Giacomo Pozza have nothing to disclose. Laura Albini and Gabriele Forcina are employees of, and hold stock in, Gilead Sciences. Role of sponsor: The study protocol was developed by the sponsor and submitted to the Ethics Committee. Data were collected as part of routine clinical practice and extracted from the institutional database (dbSacco). Data extraction and statistical analyses were performed exclusively by the investigators. The manuscript was drafted by the authors. The sponsor was given the opportunity to review the manuscript for accuracy prior to submission but had no role in data analysis, interpretation of the results, or the decision to submit the manuscript for publication.

Ethical Approval

The study was conducted in accordance with the principles of the Declaration of Helsinki and was approved by the local Ethics Committee (protocol no. CET 256–2024). Given the retrospective design and the use of anonymised data, the requirement for informed consent was waived. Patient consent was waived due to the retrospective nature of the study and anonymised data collection.