Abstract
Background
Phase 3 trials have established the long-term efficacy and safety of BIC/FTC/TAF for both treatment-naïve and treatment-experienced people with HIV (PWH). Real-world evidence in patients with very high baseline viral load remains limited.
Methods
This was a non-interventional, observational, retrospective analysis across 33 tertiary centers participating in the KLIMIK HIV-TR cohort. Adults (≥ 18 years) who initiated single-tablet BIC/FTC/TAF on or before August 31, 2022 were included. The primary endpoint was virological suppression at week-48, defined as HIV-1 RNA < 200 copies/mL. Suppression was further stratified by baseline viral load (< 100,000; > 100,000; > 1,000,000 copies/mL).
Results
2262 patients were analyzed (1122 treatment-naïve [49.6%], 1140 treatment-experienced [50.4%]). Among treatment-naïve patients, 88.5% had baseline HIV-1 RNA > 100,000 copies/mL and 24.2% > 1,000,000 copies/mL; 55.7% had CD4 < 350 cells/mm3. Virological suppression (HIV-1 RNA < 200 copies/mL) in treatment-naïve patients was 95.6% and 98.3% at weeks 24 and 48 respectively. When a threshold of < 50 copies/mL was applied, virological suppression rates at weeks 24 and 48 were 81.9% and 93%, respectively. At week 24, virological suppression (HIV-1 RNA < 50 copies/mL) was lower in those with baseline HIV-1 RNA > 100,000 versus < 100,000 copies/mL (80.4% vs. 93.8%; p < 0.001), and lower in those with baseline HIV-1 RNA > 1,000,000 versus < 1,000,000 copies/mL (67.1% vs. 86.9%; p < 0.001). The median CD4/CD8 ratio in treatment-naïve patients increased from 0.44 at baseline to 1.06 at week 48 (p < 0.001). In treatment-experienced patients, week 48 virological suppression was 92.2% (HIV-1 RNA < 50 copies/mL) and 96.5% (HIV-1 RNA < 200 copies/mL). No serious adverse events leading to discontinuation were observed.
Conclusions
High virological suppression rates were observed among both treatment-naïve patients with very high baseline viral loads and treatment-experienced patients, supporting the effectiveness and safety profile of BIC/FTC/TAF in routine clinical practice.
Background
Effective antiretroviral therapy (ART) plays a crucial role in controlling the HIV epidemic, reducing morbidity and mortality, and enabling life expectancy comparable to that of people without HIV. The introduction of integrase strand transfer inhibitors (INSTIs) has been a major advance in ART [1].
Bictegravir is a second-generation INSTI co-formulated with emtricitabine and tenofovir alafenamide (BIC/FTC/TAF), recommended as a preferred initial regimen in international guidelines [2, 3].
Phase 3 studies have demonstrated durable efficacy and safety of BIC/FTC/TAF in both treatment-naive and treatment-experienced PWH [4–8].
Switch studies have shown non-inferior outcomes versus protease-inhibitor-based or dolutegravir-based regimens [9–12].
Real-world cohorts generally report high suppression rates, but often include relatively few treatment-naïve patients with very high baseline viral load [13, 14]. We aimed to evaluate 12-month effectiveness and tolerability of BIC/FTC/TAF in routine practice across Türkiye, using data from the Turkish HIV-TR Cohort, with a specific focus on outcomes of patients with high baseline viral load.
Methods
Study design and setting
We conducted a retrospective, non-interventional, observational cohort study across 33 tertiary centers participating in the KLIMIK HIV-TR network, representing diverse geographic regions. Ethics approval was obtained from the Bursa Uludağ University Faculty of Medicine Clinical Research Ethics Committee (November 7, 2023; 2023-23/22). This study was funded by Gilead Sciences.
Participants
This study is a retrospective, non-interventional, multicenter study based on the KLIMIK HIV-TR Cohort database. Participating centers recorded all adult patients (≥ 18 years) who initiated the BIC/FTC/TAF single-tablet regimen in routine clinical practice. Eligible participants comprised all adult patients (≥ 18 years) who initiated BIC/FTC/TAF during the study period. Patients meeting the inclusion criteria were consecutively enrolled at each participating center without additional selection, in order to minimize selection bias and to ensure representativeness of real-world clinical practice. According to the predefined study protocol, only patients who initiated treatment before September 1, 2022 and had at least 12 months of follow-up were included in the analysis. This design was chosen to allow a standardized evaluation of week 48 virological outcomes. A total of 405 patients were not included in the final analysis as they had initiated BIC/FTC/TAF after September 1, 2022 and had not yet reached the predefined minimum follow-up duration of 48 weeks at the time of data cutoff. These exclusions were implemented in accordance with the study design to ensure consistent evaluation of week-48 outcomes. Given the retrospective nature of the cohort, detailed information regarding early treatment discontinuation, mortality, or loss to follow-up within this subgroup was not systematically available and is therefore acknowledged as a limitation.
Data captured included demographics, transmission category, opportunistic infections (CDC criteria), laboratory findings (including complete blood count, total cholesterol, HDL, LDL, triglycerides, non-HDL cholesterol [total cholesterol minus HDL], urea, creatinine), virological and immunological parameters, prior and current ART, and serious adverse events leading to ART discontinuation. Patients with an acute or recent infection were diagnosed with a primary/early infection. Acute infection was diagnosed when HIV(p24 Ag and/or HIV-1 RNA) was detected in the absence of HIV antibodies. Recent infection was diagnosed when HIV antibodies were detected within 6 months after infection [2, 3]. The flow of participants is presented in Fig. 1.
Fig. 1.
Flowchart of the study. *Patients were mainly not included due to insufficient duration of follow-up at the time of data cut-off. Early treatment discontinuation and loss to follow-up could not be systematically evaluated and are addressed in the limitations. **Data from patients who did not attend the Week 24 follow-up visit or who arrived outside the scheduled visit window were not included in the Week 24 analysis. Therefore, the number of patients included in the Week 24 assessment was lower than the number of patients evaluated in the virologic suppression analysis at Week 48, which was the study’s primary endpoint. Sample size differences reflect an available-case analysis based on predefined follow-up windows at weeks 4–8, 24 and 48
Outcomes
The primary endpoint was virological suppression at week 48 defined as HIV-1 RNA < 200 copies/mL. In treatment-naïve patients, suppression at weeks 4–8, 24, and 48 was also assessed using a threshold of < 50 copies/mL. Analyses were stratified by baseline viral load (< 100,000; > 100,000; > 1,000,000 copies/mL).
Secondary endpoints included change in CD4 count, increase in CD4/CD8 ratio, tolerability, and discontinuations due to drug-related adverse events. For treatment-experienced patients, reasons for switching to BIC/FTC/TAF were recorded.
Statistical analysis
Statistical analyses were performed using IBM SPSS Statistics for macOS, version 29.0 (IBM Corp., Armonk, NY, USA). In all analyses, a two-sided p value < 0.05 was considered statistically significant. Patients were evaluated in two main groups: treatment-naive (TN) and treatment-experienced (TE). Categorical variables were presented as number and percentage [n (%)], while continuous variables were summarized as median (25th–75th percentile range; IQR), minimum, and maximum values. Age was additionally reported as mean ± standard deviation.
Baseline demographic, epidemiological, virological, and immunological characteristics were described separately for the TN and TE groups. CD4 count, CD4/CD8 ratio, and HIV-1 RNA levels were presented as median (Q25–Q75); additionally, categorical classifications based on clinically meaningful threshold values were reported as frequencies and percentages. In treatment-naive patients, virological suppression rates at weeks 24 and 48 were calculated as percentages according to the HIV-1 RNA thresholds of < 50 copies/mL and < 200 copies/mL. Subgroup analyses were performed according to baseline viral load categories.
Changes in biochemical parameters between baseline and week 48 were evaluated using paired measurements. As the data showed a non-parametric distribution, changes between baseline and follow-up measurements were analyzed using the Wilcoxon signed-rank test. Patients without available laboratory or virological measurements within the predefined follow-up time windows were considered missing for that specific time point and were excluded only from the corresponding analysis (available-case analysis, missing and excluded, M = E). No imputation method was applied for missing data. Reasons for treatment discontinuation and reasons for switching to BIC/FTC/TAF in treatment-experienced patients were evaluated using descriptive analyses only and were reported as numbers and percentages.
To identify factors affecting virological suppression status at week 48 in treatment-naive patients, multivariable logistic regression analyses including age at diagnosis, sex, baseline CD4 cell count, and baseline log10 HIV-1 RNA levels were performed separately for two different virological suppression thresholds: < 50 copies/mL and < 200 copies/mL.
Results
Baseline characteristics
Of 2667 individuals recorded in the electronic data system, 2262 met inclusion criteria (1122 treatment-naïve; 1140 treatment-experienced). The baseline demographic, epidemiological, virological and immunological characteristics of treatment-naïve and treatment-experienced patients prior to initiating BIC/FTC/TAF are presented in Table 1.
Table 1.
Baseline demographic, epidemiological, virological and immunological characteristics of treatment-naïve and treatment-experienced patients prior to initiating BIC/FTC/TAF
| Parameters | Treatment-naïve (n = 1,122) | Treatment-experienced (n = 1,140) | p value |
|---|---|---|---|
| Age, years, median (range) | 33 (18–73) | 35 (18–78) | 0.021 |
| Male sex, n (%) | 1,001 (89.2) | 1,001 (87.8) | 0.294 |
| History of primary/early HIV infection, n (%) | 215 (19.2) | 143 (12.5) | < 0.001 |
| Mode of transmission, n (%) | |||
| MSM/bisexual | 282 (25) | 335 (29.4) | 0.023 |
| Heterosexual | 417 (37.2) | 493 (43.2) | 0.003 |
| Unknown | 368 (32.8) | 279 (24.5) | < 0.001 |
| Othera | 55 (5) | 33 (2.9) | 0.014 |
| CD4 count, cells/mm3, median (Q25–Q75) | 316 (183–488) | 578 (356–805) | < 0.001 |
| CD4 < 200 cells/mm3, n (%) | 307 (27.4) | 132 (11.6) | < 0.001 |
| CD4 < 350 cells/mm3, n (%) | 625(55.7) | 277(24.3) | < 0.001 |
| CD4/CD8 ratio, median (Q25–Q75) | 0.44 (0.30–0.71) | 0.85 (0.47–1.22) | < 0.001 |
| HIV-1 RNA log10 copies/mL, median (Q25–Q75) | 5.65 (5.21–5.99) | N.D.b | – |
| HIV-1 RNA > 100,000 copies/mL, n (%) | 993 (88.5) | 18 (1.6) | < 0.001 |
| HIV-1 RNA > 500,000 copies/mL, n (%) | 521 (46.4) | 0 (0.0) | < 0.001 |
| HIV-1 RNA > 1,000,000 copies/mL, n (%) | 272 (24.2) | 0 (0.0) | < 0.001 |
a "Other" includes intravenous drug use, blood/blood products, pregnancy/lactation, nosocomial transmission, and other unspecified routes
b N.D. Not determined (most treatment-experienced patients had HIV-1 RNA < 50 copies/mL at baseline)
p values were calculated using the chi-square test for categorical variables and the Mann–Whitney U test for continuous variables, p<0.05 is significant
Comorbidities included hypertension (n = 109), cardiovascular disease (n = 34), type 2 diabetes mellitus (n = 61), renal impairment (n = 17), liver disease (n = 17), and hyperlipidemia (n = 116).
Mean numbers of HIV-1 RNA measurements during follow-up were 3.0 in treatment-naïve and 2.7 in treatment-experienced patients. In treatment-naïve and treatment-experienced patients, HBsAg positivity was 3.2% and 5.2%; anti-HCV positivity was 2.1% and 1.1%; RPR positivity was 24.0% and 16.1%, respectively. Latent tuberculosis was screened using PPD or Quantiferon tests; and identified in 8.1% (19/234 screened) of treatment-naïve and 21.4% (62/290 screened) of treatment-experienced patients.
Among treatment-naïve patients, 88.5% had baseline HIV-1 RNA > 100,000 copies/mL and 24.2% > 1,000,000 copies/mL; 55.7% had CD4 < 350 cells/mm3 at baseline(Table 1).
Treatment effectiveness
Virological and immunological outcomes
Treatment-Naïve patients
In treatment-naïve patients, virological suppression rates (HIV-1 RNA < 200 copies/mL) were 95.6% at week 24 and 98.3% at week 48. When a threshold of < 50 copies/mL was applied, virological suppression rates at weeks 24 and 48 were 81.9% and 93%, respectively.
Virological suppression rates and suppression rates by baseline viral load in treatment-naive patients are presented in Figs. 2 and 3.
Fig. 2.
Virological suppression in treatment-naïve patients at weeks 4–8, 24 and 48. A HIV-1 RNA < 50 copies/mL. B HIV-1 RNA < 200 copies/mL. (Bar labels indicate the number of patients achieving virological suppression over the number of patients evaluated at each time point (n/N). Sample size differences across time points reflect an available-case analysis using predefined follow-up windows)
Fig. 3.
Virological suppression in treatment-naïve patients stratified by baseline HIV-1 RNA category at weeks 4–8, 24 and 48. A Baseline HIV-1 RNA < 100,000 copies/mL. B Baseline HIV-1 RNA > 100,000 copies/mL. C Baseline HIV-1 RNA < 1,000,000 copies/mL. D Baseline HIV-1 RNA > 1,000,000 copies/mL. (Bar labels indicate the number of patients achieving virological suppression over the number of patients evaluated at each time point (n/N). Sample size differences across time points reflect an available-case analysis using predefined follow-up windows)
Among treatment-naive patients with baseline HIV-1 RNA > 100,000 copies/mL, the virological suppression rate (HIV-1 RNA < 50 copies/mL) at week 24 was significantly lower compared to those with baseline HIV-1 RNA < 100,000 copies/mL (80.4% vs. 93.8%, p < 0.001). When using a threshold of < 200 copies/mL, virological suppression rates at week 24 were 95% and 100%, respectively (p = 0.028). No significant difference was observed in virological suppression rates according to < 50 copies/ml and < 200 copies/ml at week 48(92.5% vs. 96.7%, p = 0.127 and 98% vs. 100%, p = 0.254, respectively) in our study.
Among treatment-naive patients with baseline HIV-1 RNA > 500,000 copies/mL, the virological suppression rates (HIV-1 RNA < 50 copies/mL) at week 24 and 48 were 72.3 and 91.1%.
Among treatment-naive patients with baseline HIV-1 RNA > 1,000,000 copies/mL, virological suppression rates (HIV-1 RNA < 50 copies/mL) at weeks 24 and 48 were significantly lower compared to those with HIV-1 RNA < 1,000,000 copies/mL (67.1% vs. 86.9%, p < 0.001 and 88.4% vs. 94.5%, p = 0.002, respectively). When using a threshold of HIV-1 RNA < 200 copies/mL, the virological suppression rate at week 24 was 91.4% in patients with baseline HIV-1 RNA > 1,000,000 copies/mL and 97% in those with < 1,000,000 copies/mL (p < 0.001). At week 48, there was no significant difference in virological suppression rates between the two groups (98.4% vs. 98%, p = 0.780).
Among treatment-naive patients (n = 36) with baseline HIV-1 RNA > 5,000,000 copies/mL, virological suppression rates at week 48 (HIV-1 RNA < 50 copies/mL and < 200 copies/mL) did not differ significantly from those with baseline HIV-1 RNA < 5,000,000 copies/mL (85.3% vs. 93.3%, p = 0.083 and 94.1% vs. 98.4%, p = 0.114, respectively). Among five treatment-naïve patients with baseline HIV-1 RNA > 10,000,000 copies/mL; all patients achieved virological suppression (HIV-1 RNA < 50 copies/mL) at week 48 (Table 2).
Table 2.
Virological suppression according to baseline HIV-1 RNA level in treatment-naïve PWH
| Baseline HIV-1 RNA category | Week 24 HIV-1 RNA < 50 copies/mL (%) | Week 24 HIV-1 RNA < 200 copies/mL (%) | Week 48 HIV-1 RNA < 50 copies/mL (%) | Week 48 HIV-1 RNA < 200 copies/mL (%) |
|---|---|---|---|---|
| > 100,000 copies/mL (n = 993) | 80.4 | 95.0 | 92.5 | 98.0 |
| > 500,000 copies/mL (n = 521) | 72.3 | 93.1 | 91.1 | 97.5 |
| > 1,000,000 copies/mL (n = 272) | 67.1 | 91.4 | 88.4 | 98.0 |
| > 5,000,000 copies/mL (n = 36) | 53.1 | 90.6 | 85.3 | 94.1 |
| > 10,000,000 copies/mL (n = 5) | 60.0 | 100.0 | 100.0 | 100.0 |
Multivariable logistic regression analysis demonstrated that higher baseline log10 HIV-1 RNA level was independently associated with failure to achieve virological suppression below 50 copies/mL at week 48 among treatment-naive patients (OR = 2.048, p = 0.020). No independent association was observed for age, sex, or baseline CD4 count. In the model evaluating HIV-1 RNA > 200 copies/mL, no independent predictor reached statistical significance.
Among treatment-naive patients with a baseline CD4 count < 350/mm3, virological suppression rates (HIV-1 RNA < 50 copies/mL) at weeks 24 and 48 were significantly lower compared to those with CD4 counts > 350/mm3 (77.3% vs. 87.9%, p < 0.001 and 90.8% vs. 95.7%, p = 0.002, respectively).
Among treatment-naive patients with a CD4 count < 350/mm3 and baseline HIV-1 RNA > 100,000 copies/mL, virological suppression rates at week 24 were 76.1% and 93.3% using thresholds of < 50 copies/mL and < 200 copies/mL, respectively. At week 48, the corresponding suppression rates were 90.8% and 97.6%. When compared to patients with baseline HIV-1 RNA < 100,000 copies/mL, virological suppression rates at week 24 (using a threshold of < 50 copies/mL) were significantly lower (76.1% vs. 92.5%, p = 0.029).
Among treatment-naive patients with a CD4 count < 350 cells/mm3 and baseline HIV-1 RNA > 1,000,000 copies/mL, virological suppression rates at week 24 were 65% and 89.6% using thresholds of < 50 copies/mL and < 200 copies/mL, respectively. At week 48, the corresponding suppression rates were 85.9% and 97.3%. Compared to patients with baseline HIV-1 RNA < 1,000,000 copies/mL, virological suppression rates (threshold < 50 copies/mL) at both week 24 and week 48 were significantly lower (65% vs. 83.5%, p < 0.001; and 85.9% vs. 93.1%, p = 0.008, respectively).
Among patients with CD4 counts > 350/mm3, only those with baseline HIV-1 RNA > 1,000,000 copies/mL had lower virological suppression rates (threshold < 50 copies/mL) at week 24 compared to those with baseline HIV-1 RNA < 1,000,000 copies/mL (73.3% vs. 90.3%, p < 0.001).
Among patients with CD4 counts < 200/mm3, the virological suppression rate (HIV-1 RNA < 50 copies/mL) at week 48 was 91.6 and 93.5% with baseline CD4 counts > 200/mm3 (p = 0.333). Among patients with CD4 counts < 200/mm3 and HIV-1 RNA > 1,000,000 copies/mL, the virological suppression rate (HIV-1 RNA < 50 copies/mL) at week 48 was 87.8%.
In treatment-naïve patients, the median CD4/CD8 ratio increased from 0.44 at baseline to 1.06 at week 48 (p < 0.001) (Fig. 4A).
Fig. 4.
CD4 count and CD4/CD8 ratio over follow-up in treatment-naïve PWH (A) and treatment-experienced PWH (B) receiving BIC/FTC/TAF. Blue lines represent median CD4 count (cells/mm3) and purple lines represent median CD4/CD8 ratio at the available study time points. In both treatment-naïve and treatment-experienced PWH, changes from baseline in CD4 count and CD4/CD8 ratio were statistically significant at all available follow-up time points (p < 0.001)
Change in CD4 count (ΔCD4 [cells/mm3]) had median (25th–75th) values of + 139 (9.5–263.1) at weeks 4–8, + 216 (85.75–358) at week 24, and + 263 (91–416.5) at week 48; mean (± SD) changes were + 136.3 ± 211.7, + 244.7 ± 355.6, and + 305.7 ± 560.9, respectively.
Treatment-experienced patients
Before switching to BIC/FTC/TAF, HIV-1 RNA levels were below 50 copies/ml in 85.6% of treatment-experienced patients and below 200 copies/ml in 92.5% of them.
In treatment-experienced (switch) patients, week-48 suppression was 92.2% (< 50 copies/mL) and 96.5% (< 200 copies/mL), compared to 85.6% and 92.5%, respectively, prior to switching.
In treatment-experienced patients, the median CD4/CD8 ratio increased from 0.85 at baseline to 1.08 at week 48 (p < 0.001) (Fig. 4B).
In treatment-experienced patients, ΔCD4 median values were − 26.5 (− 256.5 to 159.25) at weeks 4–8, + 86 (− 100.0 to 257.0) at week 24, and + 117.5 (− 70.5 to 320.25) at week 48; mean changes were + 67.6 ± 376.1, + 72.1 ± 369.9, and + 125.3 ± 370.8, respectively.
Virological and immunological outcomes in primary/early infection and older age
Among 215 treatment-naïve patients with primary/early infection, median CD4 was 310 (169–456) cells/mm3; 57% had CD4 < 350 and 31.2% < 200 cells/mm3 at baseline. Baseline HIV-1 RNA > 100,000 and > 1,000,000 copies/mL occurred in 93% and 28.4%, respectively. Virological suppression at week 24 was 78.9% (< 50 copies/mL) and 96.3% (< 200 copies/mL); at week 48, corresponding suppression rates were 93.1% and 98.5%, respectively. Outcomes at week 48 were comparable to treatment-naïve patients without primary/early infection.
Among 68 treatment-naïve patients aged ≥ 50 years, week-48 virological suppression was 95% (< 50 copies/mL) and 99% (< 200 copies/mL).
Safety and tolerability
Baseline and week-48 ALT, creatinine, and lipid parameters are summarized in Table 3. Non-HDL cholesterol decreased significantly at week 48; total cholesterol/HDL ratios were comparable. Statin use during follow-up was 8.5% (95/1122) among treatment-naïve and 8.7% (99/1140) among treatment-experienced patients.
Table 3.
Biochemical parameters before BIC/FTC/TAF initiation and at week 48 of treatment
| Parameters | N | Before BIC/FTC/TAF | Week 48 | p-value | |
|---|---|---|---|---|---|
| Median (Q25–Q75) | Median (Q25–Q75) | ||||
| Treatment-Naive | ALT | 958 | 23 (18–29) | 21 (14–29.1) | < 0.001 |
| Creatinine | 987 | 0.83 (0.70–0.98) | 0.90 (0.78–1.00) | < 0.001 | |
| Non-HDL cholesterol | 918 | 125 (97–157) | 120 (104–169) | < 0.001 | |
| Total cholesterol/HDL ratio | 918 | 4.08 (3.25–4.93) | 3.93 (3.23–4.93) | 0.998 | |
| Treatment-Experienced | ALT | 1027 | 23 (18–28) | 22 (16–30.4) | 0.137 |
| Creatinine | 1043 | 0.90 (0.75–1.05) | 0.90 (0.80–1.00) | 0.001 | |
| Non-HDL cholesterol | 943 | 140 (106–171) | 126 (104–176) | < 0.001 | |
| Total cholesterol/HDL ratio | 943 | 4.05 (3.17–4.93) | 3.93 (3.24–4.98) | 0.839 | |
Treatment discontinuation
No serious adverse events leading to discontinuation were recorded. BIC/FTC/TAF discontinuation occurred 1.7% of treatment naïve and 2.6% of treatment experienced patients (Table 4).
Table 4.
Reasons for BIC/FTC/TAF discontinuation
| Reason for discontinuation | Treatment-naïve PWH (n = 19) n (%) | Treatment-experienced PWH (n = 30) n (%) |
|---|---|---|
| Patient's decision | 6 (31.6) | 2 (6.7) |
| Pregnancy | 5 (26.3) | 2 (6.7) |
| Physician's discretion | 2 (10.5) | 3 (10.0) |
| Unknown | 2 (10.5) | 13 (43.3) |
| Prevent potential future toxicities | – | 5 (16.7) |
| Other | 4 (21.1) | 5 (16.7) |
Percentages are calculated within each treatment group among patients who discontinued BIC/FTC/TAF
Previous ART in treatment-experienced patients
Among treatment-experienced patients, prior regimens before switching to BIC/FTC/TAF were as follows: elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide in 729 patients (64%), elvitegravir/cobicistat/embtricitabine/tenofovir disoproxil fumarate in 114 patients (10%), dolutegravir-based regimens in 193 patients (16.9%), raltegravir-based regimens in 26 patients (2.2%), protease inhibitor-based regimens in 57 patients (4.9%), and other regimens in 23 patients (2%). The median duration of previous ART use before switch was 48 months (IQR: 29–72).
Reasons for switching to BIC/FTC/TAF in treatment-experienced patients
In treatment-experienced patients, the most common reasons for switching to BIC/FTC/TAF were physician discretion, prevention of potential future toxicities, and treatment simplification (Table 5).
Table 5.
Reasons for switching to BIC/FTC/TAF in treatment-experienced PWH (n = 1140)
| Reason for switching to BIC/FTC/TAF | n (%) |
|---|---|
| Physician's discretion | 406 (35.6) |
| Prevent potential future toxicities | 303 (26.6) |
| Treatment simplification | 128 (11.2) |
| Other | 91 (8.0) |
| Unknown | 70 (6.1) |
| Patient's decision | 51 (4.5) |
| Drug–drug interactions | 29 (2.5) |
| Adherence issues | 19 (1.6) |
| Intolerance/toxicity | 16 (1.4) |
| Virological failure | 10 (0.9) |
| Planned treatment interruption | 5 (0.4) |
| Nephrotoxicity | 4 (0.4) |
| Enhance resistance barrier | 4 (0.4) |
| Immunological failure | 4 (0.4) |
Discussion
Virological suppression
In our study, which included a considerable proportion of treatment-naive PWH with high baseline viral loads, BIC/FTC/TAF demonstrated high rates of virological suppression at both week 24 and week 48. Virological suppression rates were 95.6% and 98.3%, respectively, when using a threshold of < 200 copies/mL, and 81.9% and 93% when using a threshold of < 50 copies/mL. Real-world studies of BIC/FTC/TAF have reported virological suppression rates at week 48 (threshold < 50 copies/mL) ranging between 91.8% and 94% [13–17]. In a meta-analysis of real-world studies, the virological suppression rate at week 48 (threshold < 50 copies/mL) was reported as 97% [18]. In phase 3 studies of BIC/FTC/TAF, efficacy at week 48 in treatment-naive patients ranged from 89 to 92.4% (threshold < 50 copies/mL) [4, 6].
To date, both clinical trials and real-world studies have included a lower proportion of treatment-naive patients with high baseline viral loads compared to our study. An evaluation of the viral loads of patients included in the study indicates that baseline viral loads were higher compared to those reported in other studies [4, 6, 13–16, 19, 20]. In real-world studies, the proportion of treatment-naive patients with baseline HIV-1 RNA > 100,000 c/mL ranges between 37.1 and 58.6%. [13–16, 19, 20]. In clinical trials, this proportion was reported at 17%, whereas in our study it was 88.5% [4, 6]. In real-world studies, the proportion of patients with HIV-1 RNA > 500,000 c/mL was reported as 18.7 and 22% in two separate studies, while a phase 3 study reported 4% of patients with HIV-1 RNA > 400,000 c/mL [6, 15, 20]. In our study, the proportion of patients with baseline HIV-1 RNA > 500,000 c/mL was 46.4% (n = 521), and 24.2% (n = 272) of patients had HIV-1 RNA > 1,000,000 c/mL at baseline. We consider that the higher rates observed may be due to the high rate of late presentation in our cohort (with 51.5% of patients in the primary/early infection–negative group having a CD4 count < 350/mm3) as well as the high proportion of primary/early infection cases.
In our study, among treatment-naive patients with baseline HIV-1 RNA > 100,000 copies/mL, the virological suppression rate (HIV-1 RNA < 50 copies/mL) at week 24 was significantly lower compared to those with baseline HIV-1 RNA < 100,000 copies/mL (80.4% vs. 93.8%, p < 0.001). In a study by Crupi et al., the virological suppression rate at week 24 (< 50 copies/ml) was reported as 85.9% in patients with HIV-1 RNA > 100,000 copies/ml [19].
Begovac et al. reported virological suppression rates at week 48 (< 50 copies/ml) of 81% and 100% (p = 0.001) in patients with HIV-1 RNA > 100,000 copies/ml and ≤ 100,000 copies/ml, respectively [20]. Hidalgo-Tenorio et al. reported virological suppression rates at week 48 (< 50 copies/ml) of 93.5% and 96% (p = 0.45) in patients with HIV-1 RNA > 100,000 copies/ml and < 100,000 copies/ml, respectively [21]. No significant difference was observed in virological suppression rates (< 50 copies/ml) at week 48 (92.5% vs. 96.7%, p = 0.127) in our study.
Gan et al. reported a virological suppression rate at week 48 (< 50 copies/ml) of 80% in 30 patients with HIV-1 RNA ≥ 500,000 copies/ml [22]. Yang et al. reported virological suppression rate at week 48 (< 50 copies/ml) of 91.2% in 34 patients with HIV-1 RNA ≥ 500,000 copies/ml [23]. Among treatment-naive 521 patients with baseline HIV-1 RNA > 500,000 copies/mL, the virological suppression rate (HIV-1 RNA < 50 copies/mL) at week 48 was 91.1% in our study. Our results were consistent with study of Hidalgo-Tenorio et al. and Yang et al. [21, 23]. On the other hand, factors such as patients accessing treatment early or late, the condition of the immune system, the presence of opportunistic infections, differences in baseline viral load, and issues with adherence to treatment may explain the low virological suppression observed in other studies.
In our study, baseline HIV-1 RNA levels > 100,000 c/mL and > 1,000,000 c/mL were found to significantly affect virological suppression rates at week 24. A similar pattern was observed in patients with higher baseline viral loads. Our findings support that in patients with high baseline viral loads, virological suppression may not be achieved by week 24, but may be achieved at substantially higher rates by week 48. Notably, despite the markedly higher proportion of treatment-naive patients with high baseline viral loads compared to other studies, the achievement of virological suppression rates comparable to those reported in the literature highlights the high efficacy of BIC/FTC/TAF. These findings suggest delayed viral suppression may occur in patients with very high baseline viral loads, and careful longitudinal assessment of viral load trajectories and adherence remains important before considering treatment modification.
Regarding the potential impact of baseline CD4 counts on this outcome, the proportion of patients with baseline CD4 < 350/mm3 ranged from 33 to 35% in phase 3 studies and from 47.4 to 57% in real-world studies. The proportion of patients with CD4 counts < 200/mm3 ranged from 11 to 14% in phase 3 studies and from 27.4% to 42% in real-world studies [4, 6, 13–16]. In our study, these proportions were 55.7% and 27.4%, respectively.
In a subgroup analysis of two Phase 3 studies, Rampogal et al. reported a virological suppression rate (< 50 copies/mL) of 99% at week 48 among 73 treatment-naive patients with baseline CD4 counts < 200/mm3. Among 39 patients with CD4 counts < 200/mm3 and HIV-1 RNA ≥ 100,000 c/mL, the virological suppression rate was reported as 97% [24]. Hidalgo-Tenorio et al. reported the rates of virological suppression at week 48 (< 50 copies/ml) as 95.1% in patients with CD4 counts < 200/mm3 and 94.9% in those with > 200/mm3 (p = 0.95) [21]. Gan et al. reported these rates as 80% and 85.2%, respectively, while Yan et al. reported them as 93.5% and 100% [22, 23]. Corona et al. reported a virological suppression rate of 86.1% at week 48 in late presenters [25]. The virological suppression rate at week 48 was 91.6% in treatment-naive patients with baseline CD4 counts < 200/mm3 and 93.5% with baseline CD4 counts > 200/mm3 (p = 0.333) in our study. In our study, the association between a baseline CD4 count < 350/mm3 and lower virological suppression rates at week 48—compared to patients with CD4 counts > 350/mm3 remained significant across all baseline viral load levels. All these results suggest that a low CD4 count may affect virological suppression despite potent antiretroviral therapy, supporting that this should also be taken into consideration when monitoring virological suppression.
Immune recovery
In our study, the median increase in CD4 count at week 48 in treatment-naïve patients was + 263 (IQR 91–416.5) and the mean increase was + 305.7 ± 560.9. In phase 3 studies, this increase ranged from + 180 to + 233, while in the real-world BICSTaR study, the median increase was + 214 (IQR 120–380). In the BICSTaR study, the proportion of patients with CD4 < 200/mm3 was 27.4%, and the proportion with CD4 < 350/mm3 was 47.4%. The proportion of patients with HIV-1 RNA > 100,000 c/mL was reported as 37.1% [13]. In Phase 3 studies, the proportion of patients with CD4 counts < 200/mm3 ranged from 11 to 14%, and those with CD4 counts < 350/mm3 ranged from 33 to 35%. The proportion of patients with HIV-1 RNA > 100,000 c/mL was reported to range from 17 to 21% [4, 6, 13]. In our study, 55.7% of treatment-naive patients had CD4 counts < 350/mm3, 27.4% had CD4 counts < 200/mm3, and 88.5% had HIV-1 RNA levels > 100,000 c/mL. We consider that the high proportion of patients with low CD4 counts and the high rate of primary/early infection in our study may explain the significant increases observed in CD4 counts.
Primary/early infection
In a study by Ambrosioni et al., including 64 patients with primary/early infection the rate of virological supression was reported as 93% [26]. In our study, including 215 individuals with primary/early infection, the virological suppression rate (< 50 c/mL) at week 48 was comparable at 93.1%.
Treatment-experienced patients
In treatment-experienced (switch) patients, the virological suppression rate at week 48 (< 50 c/mL) was 92.2%. In real-world studies, this rate is observed to range between 93.3 and 97% [11–13, 18], while in phase 3 studies, it has been reported between 92 and 94% [9, 10].
In our study, the mean change in CD4 count at week 48 was + 125.3/mm3. In previous studies, this change has been reported to range from a mean of –31 to + 32 cells/mm3 [9–11, 13]. We consider that the duration of antiretroviral therapy prior to the switch may have contributed to these differences.
Treatment discontinuation and safety
In our study, the overall treatment discontinuation rate was 1.7% in treatment-naïve patients and 2.6% in treatment-experienced patients. Esser et al. reported treatment discontinuation rates of 5% in treatment-naïve patients and 10% in treatment-experienced patients. Nasreddine et al. reported these rates as 8.3% and 6.1%, respectively [13, 17].
In our study, no treatment discontinuations due to drug-related adverse effects were observed. In phase studies, the discontinuation rate due to adverse effects in treatment-naïve patients ranged between 0 and 2%, while in real-world studies, it was reported as 3.7% [4, 6, 17]. In the switch studies, rates between 0 and 2% were reported [9–12].
In our study, no treatment discontinuations due to treatment failure or resistance were observed. Since a substantial proportion of our treatment-experienced patients had previously received an INSTI-based regimen, the possibility of cross-resistance, although low, should be considered. On the other hand, Sax et al. reported no treatment-emergent resistance during a 5-year follow-up period [8, 27]. Similarly, a very recent study conducted in our country found no resistance associated with second-generation integrase inhibitors in treatment-naïve patients [28].
Limitations
Our study has some limitations. These include its retrospective design, lack of monitoring for mild to moderate adverse events, absence of resistance data, unmonitored weight changes in patients, and a shorter follow-up period compared to the 240-week follow-up in studies 1489 and 1490 [4, 6]. The exclusion of 405 patients who had not reached the predefined follow-up duration of 48 week represents an important limitation and may introduce selection bias, potentially leading to an overestimation of virological suppression rates. Because patients with incomplete follow-up may include those with treatment discontinuation, poor adherence, or adverse outcomes, their exclusion could bias results toward more favorable outcomes. Furthermore, due to the retrospective nature of the cohort, detailed information on early discontinuation, mortality, or transfer-out could not be systematically assessed.
However, the strengths of our study are notable. First, it represents the largest multicenter real-world study conducted in Türkiye to date on BIC/FTC/TAF, actively involving 33 centers from various geographic regions. Secondly, it is the study that has included patients with the highest baseline viral loads among all studies conducted worldwide to date. Thirdly, it provides a detailed analysis of both virological and immunological responses in treatment-naive patients with low and high baseline viral loads.
Conclusions
BIC/FTC/TAF demonstrated both safety and efficacy in treatment-naive and treatment-experienced patients. Efficacy rates were particularly high in treatment-naive patients with high baseline viral loads, supporting that it can be used safely in this population.
Acknowledgements
We would like to thank Dr. Guniz Kayahan and Dr. Ahmet Yilmaz from Gilead Sciences Türkiye for their support. We would like to thank Cem Şener from İNSİDANS for the biostatistical evaluation. AI was used for graphical abstract.
KLIMIK HIV TR Working Group: Güniz Kayahan (Gilead Sciences, Türkiye), Ahmet Yılmaz (Gilead Sciences, Türkiye), Arzu Nazlı (9 Eylül University, Faculty of Medicine, İzmir), Yeşim Yıldız (Gazi University, Faculty of Medicine, Ankara), Gönül Çiçek Şentürk (Ankara Etlik City Hospital, Ankara), Yeşim Taşova (Çukurova University, Faculty of Medicine, Adana), Selçuk Kaya (Çanakkale 18 Mart University, Faculty of Medicine, Çanakkale), Onur Kaya (Süleyman Demirel University, Faculty of Medicine, Isparta), Sıla Akhan (Kocaeli University, Faculty of Medicine, Kocaeli), Tuna Demirdal (İzmir Katip Çelebi University, Faculty of Medicine, İzmir), Çiğdem Ataman Hatipoğlu (Ankara Training and Reseacrh Hospital, Ankara), Mustafa Kemal Çelen (Dicle University, Faculty of Medicine, Diyarbakır), İlkay Karaoğlan (Gaziantep University, Faculty of Medicine, Gaziantep), Yeşim Çağlar (Balıkesir University, Faculty of Medicine, Balıkesir), Aysel Kocagül Çelikbaş (Çorum Hitit University, Faculty of Medicine, Çorum), Barçın Öztürk (Adnan Menderes University, Faculty of Medicine, Aydın), Arzu Doğru (Tuzla State Hospital, İstanbul), Petek Konya (Afyon Health Sciences University, Faculty of Medicine, Afyon), Serpil Erol (İstanbul Haydarpaşa Numune Training and Research Hospital, İstanbul), Nurgül Ceran (İstanbul Haydarpaşa Numune Training and Research Hospital, İstanbul), Elif Tigen (Marmara University, Faculty of Medicine, İstanbul), Buket Ertürk Şengel (Marmara University, Faculty of Medicine, İstanbul), Dilek Yağcı Çağlayık (Marmara University, Faculty of Medicine, İstanbul), Pınar Öngürü (İstanbul Kartal Lütfi Kırdar Training and Research Hospital, İstanbul), Gülşen Mermut (Ege University, Faculty of Medicine, İzmir), Ayşe Merve Parmaksızoğlu Aydın (Ege University, Faculty of Medicine, İzmir), Burak Sarıkaya (İstanbul Sultan Abdülhamid Han Training and Research Hospital, İstanbul), Bircan Kayaaslan (Ankara Bilkent City Hospital, Ankara), Lütfiye Nilsun Altınal (Ümraniye Training and Research Hospital, İstanbul), Ayşe Serra Özel (Ümraniye Training and Research Hospital, İstanbul), Uğur Önal (Bursa Uludağ University, Faculty of Medicine, Bursa), Taner Yıldırmak (Okmeydanı Training and Research Hospital, İstanbul), Arzu Kantürk (Okmeydanı Training and Research Hospital, İstanbul), Zarife Abdulleyeva (İstanbul University, Faculty of Medicine, İstanbul), Firuze Soyak (Pamukkale University, Faculty of Medicine, Denizli), Gürsel Ersan (İzmir Tepecik State Hospital, İzmir), Güle Çınar (Ankara University, Faculty of Medicine, Ankara), İrem Akdemir Kalkan (Ankara University, Faculty of Medicine, Ankara), Ayşe Seza İnal (Çukurova University, Faculty of Medicine, Adana), Işıl Deniz Alıravcı (Çanakkale 18 Mart University, Faculty of Medicine, Çanakkale), Gül Ruhsar Yılmaz (Süleyman Demirel University, Faculty of Medicine, Isparta), Emel Azak (Kocaeli University, Faculty of Medicine, Kocaeli), Figen Kaptan (İzmir Katip Çelebi University, Faculty of Medicine, İzmir), Şerife Altun Demircan (Ankara Training and Research Hospital, Ankara), Günay Tuncer Ertem (Ankara Training and Research Hospital, Ankara), Esra Kaya Kılıç (Ankara Training and Research Hospital, Ankara), Ayşe Özlem Mete (Gaziantep University, Faculty of Medicine, Gaziantep), Özlem Akdoğan (Çorum Hitit University, Faculty of Medicine, Çorum).
Abbreviations
- BIC/FTC/TAF
Bictegravir/emtricitabine/tenofovir alafenamide
- PWH
People with HIV
- KLİMİK
Turkish Society of Clinical Microbiology and Infectious Diseases
- ART
Antiretroviral Therapy
- INSTI
Integrase Strand Transfer Inhibitors
Author contributions
HA and VK proposed and developed research question. HA wrote the first draft of the manuscript. VK conducted the critical review. All authors contributed the study design, interpretation of data and the revision of the manuscript. All authors have seen and contributed to the final version of manuscript.
Funding
This study was funded by Gilead Sciences.
Data availability
No datasets were generated or analysed during the current study.
Declarations
Ethics approval and consent to participate
Not applicable.
Competing interests
There is no competing interests.
Footnotes
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Contributor Information
Halis Akalın, Email: halis@uludag.edu.tr.
KLİMİK HIV TR Working Group - Turkish Society of Clinical Microbiology and Infectious Diseases(KLİMİK):
Güniz Kayahan, Ahmet Yılmaz, Arzu Nazlı, Yeşim Yıldız, Gönül Çiçek Şentürk, Yeşim Taşova, Selçuk Kaya, Onur Kaya, Sıla Akhan, Tuna Demirdal, Çiğdem Ataman Hatipoğlu, Mustafa Kemal Çelen, İlkay Karaoğlan, Yeşim Çağlar, Aysel Kocagül Çelikbaş, Barçın Öztürk, Arzu Doğru, Petek Konya, Serpil Erol, Nurgül Ceran, Elif Tigen, Buket Ertürk Şengel, Dilek Yağcı Çağlayık, Pınar Öngürü, Gülşen Mermut, Ayşe Merve Parmaksızoğlu Aydın, Burak Sarıkaya, Bircan Kayaaslan, Lütfiye Nilsun Altınal, Ayşe Serra Özel, Uğur Önal, Taner Yıldırmak, Arzu Kantürk, Zarife Abdulleyeva, Firuze Soyak, Gürsel Ersan, Güle Çınar, İrem Akdemir Kalkan, Ayşe Seza İnal, Işıl Deniz Alıravcı, Gül Ruhsar Yılmaz, Emel Azak, Figen Kaptan, Şerife Altun Demircan, Günay Tuncer Ertem, Esra Kaya Kılıç, Ayşe Özlem Mete, and Özlem Akdoğan
References
- 1.Peters E, Iwuji C. Efficacy, safety and tolerability of Biktarvy in HIV-1 infection: a scoping review. Antivir Ther. 2023(1). 10.1177/13596535231159030. [DOI] [PubMed]
- 2.Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents with HIV. Updated Sep 25, 2025. Accessed Dec 15, 2025.
- 3.European AIDS Clinical Society (EACS). Guidelines v13.0. Accessed Dec 15, 2025.
- 4.Gallant J, Lazzarin A, Mills A, Orkin C, Podzamczer D, Tebas P, et al. Bictegravir/emtricitabine/tenofovir alafenamide versus dolutegravir/abacavir/lamivudine for initial treatment of HIV-1 infection (GS-US-380-1489): a double-blind, multicentre, phase 3, randomised controlled non-inferiority trial. Lancet. 2017;390:2063–72. [DOI] [PubMed] [Google Scholar]
- 5.Wahl DA, Yazdanpanah Y, Baumgarten A, Clarke A, Thompson MA, Brinson C, et al. Bictegravir combined with emtricitabine and tenofovir alafenamide versus dolutegravir/abacavir/lamivudine for initial treatment of HIV-1: week 96 results from a randomised, double-blind, multicentre, phase 3, non-inferiority trial. Lancet HIV. 2019;6:e355–63. [DOI] [PubMed] [Google Scholar]
- 6.Sax PE, Pozniak A, Montes ML, Koenig E, DeJesus E, Stellbrink HJ, et al. Coformulated bictegravir, emtricitabine, and tenofovir alafenamide versus dolutegravir with emtricitabine and tenofovir alafenamide for initial treatment of HIV-1 (GS-US-380-1490): a randomised, double-blind, multicentre, phase 3, non-inferiority trial. Lancet. 2017;390:2073–82. [DOI] [PubMed] [Google Scholar]
- 7.Orkin C, DeJesus E, Sax PE, Arribas JR, Gupta SK, Martorell C, et al. Fixed-dose bictegravir/emtricitabine/tenofovir alafenamide versus dolutegravir-containing regimens for initial treatment of HIV-1 infection: week 144 results from two randomised, double-blind, multicentre, phase 3, non-inferiority trials. Lancet HIV. 2020;7:e389–400. [DOI] [PubMed] [Google Scholar]
- 8.Sax PE, Arribas JR, Orkin C, Lazzarin A, Pozniak A, DeJesus E, et al. Bictegravir/emtricitabine/tenofovir alafenamide as initial treatment for HIV-1: five-year follow-up from two randomized trials. EClinicalMedicine. 2023;59:101991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Daar ES, DeJesus E, Ruane P, Crofoot G, Oguchi G, Creticos C, et al. Switching to bictegravir/emtricitabine/tenofovir alafenamide from boosted protease inhibitor-based regimens in virologically suppressed adults with HIV-1: 48-week results of a randomised, open-label, multicentre, phase 3, non-inferiority trial. Lancet HIV. 2018;5:e347–56. [DOI] [PubMed] [Google Scholar]
- 10.Molina JM, Ward D, Brar I, Mills A, Stellbrink HJ, López-Cortés L, et al. Switching to bictegravir/emtricitabine/tenofovir alafenamide from dolutegravir plus abacavir/lamivudine in virologically suppressed adults with HIV-1: 48-week results of a randomised, double-blind, multicentre, active-controlled, phase 3, non-inferiority trial. Lancet HIV. 2018;5:e357–65. [DOI] [PubMed] [Google Scholar]
- 11.Gan L, Xie X, Fu Y, Yang X, Ma S, Kong L, et al. Bictegravir/emtricitabine/tenofovir alafenamide versus dolutegravir plus lamivudine for switch therapy in patients with HIV-1 infection: a real-world cohort study. Infect Dis Ther. 2023;12:2581–93. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12.Sax PE, Rockstroh JK, Luetkemeyer AF, Yazdanpanah Y, Ward D, Trottier B, et al. Switching to bictegravir/emtricitabine/tenofovir alafenamide in virologically suppressed adults with HIV. Clin Infect Dis. 2021;73(2):e485–93. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13.Esser S, Brunetta J, Inciarte A, Levy I, D’Arminio Monforte A, Lambert JS, et al. Twelve-month effectiveness and safety of bictegravir/emtricitabine/tenofovir alafenamide in people with HIV: real-world insights from BICSTaR cohorts. HIV Med. 2024;25:440–53. [DOI] [PubMed] [Google Scholar]
- 14.D’Arminio Monforte A, Tavelli A, Di Biaggio A, Sarmati L, Marchetti GC, Bai F, et al. Long-term outcomes of bictegravir/emtricitabine/tenofovir alafenamide as first-line therapy and as switch strategy in virologically suppressed persons with HIV: data from the ICONA cohort. J Antimicrob Chemother. 2024;79:1279–88. [DOI] [PubMed] [Google Scholar]
- 15.Torralba M, Rodríguez G, Gasca FJG, Cuadra F, Barberá J, Geijo P, et al. Bictegravir/emtricitabine/tenofovir alafenamide in a multicentre cohort: real-life experience from Spain. Ann Pharmacother. 2024;58(2):140–7. [DOI] [PubMed] [Google Scholar]
- 16.Ambrosioni J, Lievano JR, Berrocal L, Inciarte A, de la Mora L, González-Cordón A, et al. Real-life experience with bictegravir/emtricitabine/tenofovir alafenamide in a large reference clinical centre. J Antimicrob Chemother. 2022;77:1133–9. [DOI] [PubMed] [Google Scholar]
- 17.Nasreddine R, Florence E, Yombi JC, Henrard S, Darcis G, Van Praet J, et al. Efficacy, durability, and tolerability of bictegravir/emtricitabine/tenofovir alafenamide for the treatment of HIV in a real-world setting in Belgium. HIV Med. 2023;24:914–24. [DOI] [PubMed] [Google Scholar]
- 18.Chivite I, Berrocal L, de Lazzari E, Navadeh S, Lluis-Ganella C, Inciarte A, et al. Effectiveness, safety and discontinuation rates of bictegravir/emtricitabine/tenofovir alafenamide in people with HIV using real-world data: a systematic review and meta-analysis. J Antimicrob Chemother. 2024;79:1775–83. [DOI] [PubMed] [Google Scholar]
- 19.Crupi L, Parodi A, Cenderello G, Muccio M, Blanchi S, Randazzo N, et al. Impact of baseline plasma HIV-1 RNA and viral subtype on achievement of virological suppression in people with HIV treated with bictegravir/emtricitabine/tenofovir alafenamide in clinical practice. Sex Transm Infect. 2025;101(Suppl 1):A1–207. [Google Scholar]
- 20.Begovac J, Lisicar I, Pintar VR, Zidovec-Lepej S, Planinic A, Zekan S. Coformulated bictegravir, emtricitabine, and tenofovir alafenamide introduced at the first clinical visit: a real-life single-centre retrospective cohort study. Infect Dis Ther. 2025;14:867–80. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 21.Hidalgo-Tenorio C, Sequera S, Vivancos MJ, Vinuesa D, Collado A, De Los SI, et al. Bictegravir/embtricitabine/tenofovir alafenamide as first-line treatment in naïve HIV patients in a rapid-initiation model of care: BIC-NOW clinical trial. Int J Antimicrob Agents. 2024;63:107164. [DOI] [PubMed] [Google Scholar]
- 22.Gan L, Xie X, Fu Y, Yang X, Ma S, Kong L, et al. Comparison of dolutegravir+lamivudine and bictegravir/embtricitabine/tenofovir alafenamide in antiretroviral therapy-naïve patients infected with HIV: preliminary results from clinical practice. Expert Rev Anti Infect Ther. 2024;22:877–84. [DOI] [PubMed] [Google Scholar]
- 23.Yang X, Xie X, Fu Y, Gan L, Ma S, Long H. Effectiveness and safety of bictegravir/Embtricitabine/Tenofovir alafenamide in late-presenting people with HIV-1 infection. Open Forum Infect Dis. 2024;18:ofae630. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 24.Rampogal M, Wurapa A, Baumgarten A, Berhe M, Pozniak A, Orkin C, et al. Five-year outcomes of bictegravir/emtricitabine/tenofovir alafenamide as initial treatment of HIV-1 in adults with high baseline HIV-1 RNA and/or low CD4 count in two phase 3 randomized clinical trials. Presented at: IDWeek 2022; Oct 19–23, 2022; Washington, DC, USA.
- 25.Corona D, Pérez-Valero I, Camacho A, Liarte AG, Montero-Alonso M, Alemán MR, et al. Effectiveness and safety of bictegravir/emtricitabine/tenofovir alafenamide in HIV late presenters. Int J Antimicrob Agents. 2024;63:107016. [DOI] [PubMed] [Google Scholar]
- 26.Ambrosioni J, de Lazzari E, Suanzes P, Busca C, Ruperta LR, Orviz E, et al. Bictegravir/emtricitabine/tenofovir alafenamide for the treatment of primary HIV infection: the DIC-PHI clinical trial. Presented at: AIDS 2024; Jul 22–26, 2024; Munich, Germany.
- 27.Blanco-Arevalo JL, García-Deltoro M, Torralba M, Vélez-Díaz-Pallares M, Castro A, Rubio-Rodríguez D, et al. HIV-1 resistance and virologic failure to treatment with the integrase inhibitors bictegravir, cabotegravir, and dolutegravir: a systematic literature review. AIDS Rev. 2024;26:67–79. [DOI] [PubMed] [Google Scholar]
- 28.Özdemir A, Demir T, Polat C, Mertcan U, Sönmezer MÇ, Ergünay K, Ünal S, İnkaya AÇ, Pınar A. Molecular epidemiology and antiretroviral drug resistance profile, including capsid inhibitors, among treatment-naïve individuals with HIV-1 in Türkiye. HIV Med. 2025:1–9. Epub ahead of print. [DOI] [PubMed]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
No datasets were generated or analysed during the current study.