Efficacy and protective effects of urinary biomarkers among people with HIV with early or mild renal injury taking Bictegravir/Emtricitabine/Tenofovir Alafenamide (BIC/FTC/TAF): a real world study in China

doi:10.21203/rs.3.rs-8305710/v1

Objective

Our study aimed to investigate efficacy and safety of BIC/FTC/TAF among people with HIV(PWH) with early renal or mild injury after 48-week initiation.

Methods

A retrospective study conducted to evaluate the efficacy and safety of BIC/FTC/TAF in 278 ART-naïve and 44 ART-experienced PWH who received treatment at Beijing Ditan Hospital from January 2022 to December 2023..

Results

99.6% ART-naïve and 100% ART-experienced PWHs achieved virologically suppressed 48-week of initiation, including 7 ART-experienced PWHs presented NNRTI and 3TC resistance. UP/C, ACR and Urine biomarkers, including UPQ, UMA, α1-MG and β2-MG, were significantly improved after initiation, in which UP/C in ART-naive and -experienced PWH were decreased from 2.97(IQR:1.43 ~ 3.48) to 1.74(IQR:0.80 ~ 1.93) (p < 0.001) and 4.33(IQR:2.31 ~ 5.72) to 1.42 (IQR:0.78 ~ 1.37) (p < 0.001), respectively, the prevalence of CKD A2 (3 ≤ ACR ≤ 30mg/mmol) decreased from 2.6% to 0, the UPQ decreased from 21.66(IQR:10.50 ~ 22.65) mg/dl at baseline to 12.78(IQR:5.80 ~ 14.20)mg/dl at 48-week(p < 0.001), UMA from 44.77 (IQR:14.85 ~ 44.08)mg/L to 24.81(IQR:7.00 ~ 23.00)mg/L(p < 0.001), α1-MG from 16.04(0 ~ 19.43)mg/L to 9.91(0 ~ 13.50)mg/L (p < 0.001), and β2-MG from 1.26 (0.39 ~ 1.26)mg/L to 0.50(0.18 ~ 0.58)mg/L (p < 0.001), respectively. serum creatinine and eGFR presented significantly increased and reduced at 24-week, respectively, and kept stable at 48-week of initiation. Lipid panel also indicated significantly increased at 24-week and maintained stable levels at 48-week of initiation among ART-naive PWHs, while among ART-experienced PWH switching from EVG/c/FTC/TAF, lipid panel showed downward trend.

Conclusion

BIC/FTC/TAF demonstrated good efficacy and safety in ART-naive and -experienced PWH with early or mild renal injury, and the urinary biomarkers were significantly improved after receiving BIC/FTC/TAF, which indicated its renal protective effect.

HIV

Antiretroviral therapy

Renal safety

Efficiency

Early renal injury

Globally, 40.8 million individuals are currently affected by Human Immunodeficiency Virus (HIV)^[1], early initiation of antiretroviral therapy (ART) immediately following HIV diagnosis has emerged as a fundamental pillar in the contemporary management of people with HIV (PWH). Studies have demonstrated that^[2–3] initiating ART as early as possible can effectively suppress the viral load (VL), and significantly reduce the HIV-related morbidity and mortality rate^[4–5]. But compared with people without HIV, PWH are more likely to develop acute and chronic kidney disease (CKD). With the widespread use of ART, HIV-associated nephropathy(HIVAN) has become less common, but the prevalence of other kidney diseases has increased simultaneously. For PWH who require lifelong ART, CKD is more likely to occur^[6]. According to WHO^[1], with the increasing use of antiretroviral drugs (ARVs) for HIV treatment, the need to monitor efficacy and safety of ARVs has increased substantially^[7]. In addition, PWH are more likely to develop lipid metabolism disorders after receiving ART, thereby it is very necessary to study the effects of ARVs on the renal function and lipid metabolism of PWH. By monitoring renal function and specific biomarkers, early or mild renal injury can be detected ^[6–7], and timely renal protective treatment could be recommended, thereby delaying the incidence of CKD.

The estimated glomerular filtration rate (eGFR) was used to evaluate the glomerular function and played a key role in diagnosing and staging of CKD, It was reported that^[8] some special urine proteins, including urinary protein quantification(UPQ), urinary microalbumin (UMA), α1-microglobulin (α1-MG) and β2-microglobulin (β2-MG), were more sensitive biomarkers of early renal injury, which was defined as the presence of renal function or structural abnormalities that did not meet the criteria for CKD but indicated a risk of progressive kidney injury. Although different degree of renal injury, including early and mild renal injuries, often occurred among PWHs due to HIV infection or ARV regimens^[9]. It was reported that^[10] PWH with/without receiving ART presented early renal injury with normal eGFR but with abnormal special urine proteins, which indicated that it reminded physicians to choose less renal-toxicity ARV regimens among these PWH with early and mild renal injury to prevent the deterioration of renal function. Some studies have reported that^[11–12] the ARV regimen based on tenofovir disoproxil fumarate (TDF) presented significant renal toxicity. TDF, as a nucleotide reverse transcriptase inhibitor, was converted into tenofovir (TFV) in vivo to exert its effect, and TFV was mainly eliminated through glomerular filtration and active tubular secretion. Compared with TDF, tenofovir alafenamide (TAF), also a prodrug of TFV, presented significantly lower nephrotoxicity^[9][13–15]. Due to a longer half-life in plasma, the uptake of TAF increased by immune cells at a lower dose and lower plasma concentration, compared with TDF, thereby reducing the intracellular accumulation of tenofovir in proximal tubular epithelial cells (the main target of TDF nephrotoxicity)^[16]. In real-world, bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF, GileadSciences, Inc. CA, USA), one single-tablet co-formulated regimen containing TAF, is one of representative second INSTIs, has been widely used across the world, but influence of TAF on PWH with early or mild renal injury, especially normal eGFR but with proteinuria was obscured severely. This study aimed to evaluate efficacy and safety of BIC/FTC/TAF among PWH with early or mild renal injury.

Ethical consideration

This retrospective study was performed at Beijing Ditan Hospital, Capital Medical University, a specialized referral center for HIV/AIDS in China. The collection of anonymous clinical data for this study was approved by the Health Science Ethics Committee of Beijing Ditan Hospital. Utilizing an observational cohort design, the study was granted a waiver of informed consent by the ethics committee, as these anonymized data posed minimal risk to participants and the research objectives could not be achieved without the waiver.

Study population

We conducted a retrospective, self-controlled before-and-after study in 278 ART-naive PWHs who received BIC/FTC/TAF, and in 44 ART-experienced ones who switched to BIC/FTC/TAF from January 2022 to December 2023, including criteria : (1) aged > 18 years, (2) receiving BIC/FTC/TAF 48 weeks, (3) with normal eGFR but with abnormal special urine proteins, (4) with mild renal injury(eGFR: 60–89 ml/min/1.73m²), (5) without use of nephrotoxic drugs or lipid-lowering drugs within 3 months before receiving BIC/FTC/TAF; exclusion criteria : (1) treatment duration was less than 24 weeks, (2) baseline data were lacking(Fig. 1).

Clinical data collection

We extracted clinical information and laboratory test indicators at baseline, week 24 and week 48 from the de-identified electronic medical records. Demographic information included: age(years) and gender(proportion of males, n(%)); immunological and virological indicators: CD4 + T cell counts (cells/µl), CD8 + T lcell counts (cells/µl) and viral load (VL); renal function indicators: blood urea(UREA, mmol/L), serum creatinine(Cr, mmol/L) and estimated glomerular filtration rate(eGFR, ml/min/1.73m²); Urinary biomarkers including urinary protein quantification(UPQ), urinary microalbumin(UMA), α1-microglobulin(α1-MG) and β2-microglobulin(β2-MG), urine albumin/creatinine(ACR, mg/mmol) and urinary protein/creatinine(UP/C, mg/mmol) were used to evaluate the degree of renal dysfunction; blood lipid panels: total cholesterol (TC, mmol/L), triglycerides (TG, mmol/L), high-density lipoprotein cholesterol (HDL-C, mmol/L), and low-density lipoprotein cholesterol (LDL-C, mmol/L).

Clinical definition

Early renal injury was defined as the presence of renal function or structural abnormalities that do not meet the criteria for CKD (eGFR ≥ 90ml/min/1.73m²) and abnormal increased urine biomarkers^[8]. Mild renal injury was defined as stage G1 of CKD(60ml/min/1.73m² ≤ eGFR < 90 ml/min/1.73m²). ACR was used to access the degree of renal dysfunction, which was divided as: stage A1 of CKD: ACR < 3mg/mmol, stage A2 of CKD: 3 ≤ ACR ≤ 30 mg/mmol, stage A3 of CKD: ACR > 30mg/mmol. According to European AIDS Clinical Society(EACS)^[17], confirmed increase in UP/C and α1-MG or β2-MG were used to screen for tubular proteinuria secondary to drug nephrotoxicity. Urinary biomarkers, including α1-MG > 6 mg/L, β2-MG > 0.3 mg/L, UPQ > 14mg/dl, and UMA > 25mg/L were considered as positive in urine specific proteins. Dyslipidemia was defined as following: TG ≥ 2.3 mmol/L as hypertriglyceridemia, TC > 6.2 mmol/L as hypercholesterolemia, LDL > 3.12 mmol/L and HDL < 1 mmol/L.Virological success was defined as achieving an undetectable viral load (ART-naiveD), while virological failure was presented as the inability to achieve or maintain inhibition of viral replication to HIV viral load < 200copies/ml.

Assessment of changes in renal functions and lipid panel

This study was conducted among PWH with early or mild renal injury, at baseline, week 24 and week 48 after receiving BIC/FTC/TAF, the evaluation of renal function including eGFR, UREA, serum Cr, ACR, UP/C, UPQ, UMA, α1-MG, β2-MG and serum lipid panels including TG, TC, LDL and HDL were assessed.

Assessment of efficacy and safety

The HIV viral load 24-week after taking BIC/FTC/TAF among ART-naive and -experienced PWHs with early or mild renal injury was used to evaluated ART efficacy..

Besides changes in renal functions and lipid panel, evaluation of safety included gastrointestinal and neuropsychiatric symptoms, and liver functions were also evaluated at baseline, week 24 and week 48 of taking BIC/FTC/TAF.

Statistical analysis

BM SPSS Statistics for Windows, version 28.0 (IBM Corp, Armonk, NY, USA) was used for statistical study. For variables presented with a normal distribution, repeated-measures analysis of variance (ANOVA) was conducted to compare the difference at baseline, week 24, and week 48. Post-hoc pairwise comparisons (week 0 vs week 24, week 0 vs week 48) were corrected using the Scheffé method to conduct multiple testing. For variables with a non-normal distribution, non-parametric tests, including the Kruskal-Wallis test and the Mann-WhiART-naiveey U test, were conducted to detect overall differences. Quantitative data were presented as the mean ± standard deviation (SD) (for normally distributed variables) while non-normally distributed variables were presented as the median (interquartile range (IQR)). Categorical data were presented as frequencies (percentages) [n(%)]. Bar charts were used to present the alterations in renal function and blood lipids among PWHs receiving BIC/FTC/TAF, and p < 0.05 represented statistically significance.

Baseline characteristics

We screened 322 PWH with early or mild renal injury, and a total of 306 PWHs were included, among which there were 266 ART-naive and 39 ART-experienced ones. Among the ART-experienced patients, 21 patients switched from tenofovir disoproxil fumarate + lamivudine + efavirenz (TDF + 3TC + EFV) to BIC/FTC/TAF, 11 PWHs from elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (EVG/c/FTC/TAF) to BIC/FTC/TAF, 6 patients from 3TC/DTG, and 1 patient from TAF/FTC/DTG, respectively (Fig. 1). The baseline CD4 cell count was 360.16 and 551.55 cells/µl in ART-naive and ART-experienced PWHs, respectively. There were 174 PWHs (65.4%) with VL > 10,000 copies/ml in the ART-naive cohort and 7 ones (17.9%) in the ART-experienced cohorts (Fig. 1,Table.1).

The eGFR was 113.98(IQR:105.85 ~ 123.73) and 107.67(IQR:98.40 ~ 120.70)ml/min/1.73m2 in ART-naive and ART-experienced patients, separately. 247(92.9%) ART-naive patients and 32 (82.0%) ART-experienced patients had an eGFR ≥ 90 ml/min/1.73m², while 19(7.1%) ART-naive patients and 7(18.0%) ART-experienced patients had an eGFR between 60 and 89 ml/min/1.73m². According to albuminuria categories(ACR) in CKD, 159 (97.4%) ART-naive and all ART-experienced PWHs were diagnosed with stage A1 of CKD. In ART-naive, 7 (2.6%) patients were identified as stage A2 of CKD. However, all patients exhibited elevated urinary protein levels with different degrees, in which the UPQ of ART-navie patients was 21.66(IQR:10.50 ~ 22.65) mg/dl and of ART-experienced was 33.02(IQR:18.30 ~ 42.40) mg/dl. The UMA of ART-naive was 44.77(IQR:14.85 ~ 44.08) mg/L and of ART-experienced was 83.22(IQR:44.00 ~ 105.30) mg/L. The α1-MG of ART-naive was 16.04(IQR:0 ~ 19.43) mg/L and of ART-experienced was 20.82(IQR:17.40 ~ 24.40) mg/L. β2-MG of ART-naive was 1.26 (IQR:0.39 ~ 1.26) mg/L and of ART-experienced was 1.70(IQR:1.59 ~ 1.67) mg/L, separately. The prevalence of abnormal increased levels of UPQ, UMA, α1-MG and β2-MG in ART-naive patients were 65.41%, 56.39%, 67.67% and 89.97%, and in ART-experienced patients were 76.92%, 74.36%, 87.18%% and 92.31%, separately. The UP/C of ART-naive patients was 2.97(IQR:1.43 ~ 3.48) mg/mmol and of ART-experienced patients was 4.33(IQR:2.31 ~ 5.72) mg/mmol, respectively.(Table.1)

Renal safety

In ART-naive patients receiving BIC/FTC/TAF, serum creatinine was 75.04(IQR:66.15 ~ 81.83) mmol/L at baseline, and increased to 84.24(IQR:76.90 ~ 91.33)mmol/L (p < 0.001) at week 24. However, no significant difference was found in the increase of Cr at week 48 compared with that at 24 weeks (p > 0.05), which indicated it reached a stable state. While eGFR decreased from 113.98(IQR:105.85 ~ 123.73) to 103.85(IQR:93.70 ~ 115.20)ml/min/1.73m² at week 24 (p < 0.001). Similar with serum creatinine, the decrease of eGFR from week 24 to week 48 presented no significant difference. In ART-experienced patients, the changes of serum creatinine and eGFR were consistent with ART-naive patients(Fig. 2). Among patients switching from TDF + TC + EFV (n = 21) and from EVG/c/FTC/TAF to BIC/FTC/TAF(n = 11), although no significant changes were observed, the trend of change was consistent with that of ART-naive patients (Fig. 2). Overall, within 48 weeks of BIC/FTC/TAF treatment, both ART-naive and ART-experienced patients showed stable serum creatinine and eGFR levels, though significant changes were observed in these parameters before week 24.

There was improvement in ACR and UP/C after receiving BIC/FTC/TAF. The prevalence of CKD A2(3 ≤ ACR ≤ 30mg/mmol) decreased from 2.6% to 0(Fig. 3). UP/C in ART-naive and -experienced patients were decreased from 2.97(IQR:1.43 ~ 3.48) to 1.74(IQR:0.80 ~ 1.93)(p < 0.001) and 4.33(IQR:2.31 ~ 5.72) to 1.42 (IQR:0.78 ~ 1.37)(p < 0.001), separately(Fig. 4). The study indicated that UPQ, UMA, α1-MG and β2-MG were significantly improved among ART-naive PWHs after receiving BIC/FTC/TAF. The prevalence of abnormal increased levels of UPQ, UMA, α1-MG and β2-MG were decreased to 25.58%, 20.93%, 42.8% and 52.56% at 48-week, respectively (Fig. 5). The UPQ decreased from 21.66(IQR:10.50 ~ 22.65) mg/dl at baseline to 12.78(IQR:5.80 ~ 14.20)mg/dl at 48-week(p < 0.001), UMA from 44.77 (IQR:14.85 ~ 44.08)mg/L at baseline to 24.81(IQR:7.00 ~ 23.00)mg/L at 48-week(p < 0.001), α1-MG from 16.04(IQR:0 ~ 19.43)mg/L to 9.91(IQR:0 ~ 13.50)mg/L(p < 0.001), and β2-MG from 1.26 (IQR:0.39 ~ 1.26)mg/L to 0.50 (IQR:0.18 ~ 0.58)mg/L(p < 0.001), respectively(Fig. 6(a)). In ART-experienced patients, UPQ, UMA, α1-MG, and β2-MG also showed great improvement, in which UPQ decreased from 33.02(IQR:18.30 ~ 42.40)mg/dl at baseline to 11.84(IQR:6.50 ~ 12.85) mg/dl at 48-week (p < 0.05)(Fig. 6(b)), while UMA, α1-MG, and β2-MG presented downward trends, and among patients who switched from TDF + TC + EFV to BIC/FTC/TAF, the proteinuria also improved significantly (p < 0.05) from baseline, 24-week to 48-week.

Changes in Lipid metabolism

Among ART-naive patients with renal dysfunction, at baseline, 24-week and 48-week, lipid panel increased significantly after receiving BIC/FTC/TAF, in which TC presented 4.16 (IQR:3.58 ~ 4.66) at baseline, 4.49(IQR:3.88 ~ 5.00) at 24-week and 4.54 (IQR:3.91 ~ 5.12)mmol/L at 48-week, TG was 1.33 (IQR:0.80 ~ 1.65) at baseline, 1.61(IQR:0.85 ~ 1.86) at 24-week and 1.64 (IQR:0.90 ~ 1.89)mmol/L at 48-week, HDL was 0.98 (IQR:0.83 ~ 1.11), 1.09 (IQR:0.94 ~ 1.22) and 1.10 (IQR:0.94 ~ 1.22)mmol/L, and LDL was 2.60(IQR:2.14 ~ 2.95), 2.78 (IQR:2.28 ~ 3.24) and 2.84 (IQR:2.29 ~ 3.24)mmol/L, separately (Fig. 7(a)). While among ART-experienced patients, lipid panel did not presented significantly change after switching to BIC/FTC/TAF(Fig. 7(b)), in which among PWHs switching from TDF + 3TC + EFV, lipid panel showed an upward trend with no statistically significant(Fig. 7(c)), and among patients switching from TAF/FTC/EVG/c, serum TG ,TC and LDL showed a downward trend and HDL showed upward trend (Fig. 7(d)).

Efficacy

In ART-naive patients, 174 (65.4%) patients presented VL > 10,000 copies/ml, and 48-week after taking BIC/FTC/TAF, the VL of 265 PWHs (99.6%) were completely inhibited, while 1 cases presented virologic failure due to poor adherence and spontaneous discontinuation of the BIC/FTC/TAF. In ART-experienced patients, 7(17.9%) patients had a viral load > 10,000 copies/ml, and resistance test indicated that Non-nucleoside reverse transcriptase inhibitor(NNRTI) and 3TC resistance, and switched to BIC/FTC/TAF treatment. After 48 weeks of BIC/FTC/TAF treatment, these PWH all achieved virologically surppresed, which indicated that in this PWH with early and mild renal injury, BIC/FTC/TAF presented good antiviral efficacy.

Assessment of adverse effects

BIC/FTC/TAF presented well-toleration. Most adverse events were mild or moderate in severity, and no adverse events were presented to lead to drug discontinuation. Two patients (0.6%) experienced moderate gastrointestinal symptoms, including diarrhea and vomiting, after the initial dose, which gradually resolved during treatment process. Five patients(1.6%) developed neurological symptoms, presenting as headache and dizziness, both of which were mild and did not affect daily activities. One patient had sleep disorders, which were considered to be related to the habit of taking the drug before bedtime, which was alleviated after adjusting the medication time. Liver functions was also evaluated at baseline, 24-week and 48-week of taking BIC/FTC/TAF, and results were normal at these 3 time points.

This study revealed favorable clinical evidence for improved renal safety of ART-naive or -experienced patients with early or mild renal dysfunction after receiving BIC/FTC/TAF through the evaluation of renal function and proteinuria in a real-world observational cohort.

The study revealed that BIC/FTC/TAF demonstrated appreciable renal safety, among both ART-naive and ART-experienced PWHs with early or mild renal injury. We found that, among these ART-naive or -experienced patients with early or mild renal injury, serum creatinine level increased and eGFR decreased significantly 24-week after receiving BIC/FTC/TAF, and kept stable level at week 48 after initiation. It was reported that^[18–21], 85% of serum creatinine was filtered through the glomerulus, and 15% was actively secreted through some creatinine transporters (such as OCTG2) in the renal tubules, and integrase strand transfer inhibitors (INSTIs), including Bictegravir, can inhibit these transport proteins, thereby affecting the excretion of blood creatinine and resulting in increased serum creatinine levels and decreased eGFR. In this study, our finding was consistent with previous report^[18–21] and revealed good renal safety among ART-naive or -experienced patients with early or mild renal injury.

Of special significance was that this study revealed the improvement in proteinuria provided another important evidence of the renal safety of BIC/FTC/TAF. Renal dysfunction was often presented in ART-naive or -experienced population caused by HIV infection and some ART regimens^[22], and some PWHs with early or mild renal injury with abnormal proteinuria was often neglected, which resulted in continuous deterioration of renal function. Therefore, regular monitoring of urinary protein and timely switching to less renal-toxicity ARV regimens can ultimately reduce the prevalence of end-stage CKD in PWH. In this study, we found that ACR, as a biomarker of albuminuria category of CKD, improved after receiving BIC/FTC/TAF among these PWH with early or mild renal injury, and UP/C also improved significantly, which fully demonstrated that the renal function of PWH was gradually improved after receiving BIC/FTC/TAF.

This study also found that in both ART-naive and -experienced PWHs with early or mild renal injury, the abnormal increased levels of UPQ, UMA, α1-MG and β2-MG decreased significantly within 48 weeks after taking BIC/FTC/TAF. The prevalence of PWH with positive special urinary proteins also decreased significantly. In particular, the decrease in UP/C, α1-MG and β2-MG, sensitive marker of renal tubular injury, indicated that BIC/FTC/TAF had significant improvements in tubular function and alleviated the impairment to the kidneys caused by HIV infection or previous treatments, further supporting the protective effect of BIC/FTC/TAF on the renal functions among PWH with early or mild renal injury. Previous studies indicated that^[23] TDF-based treatment was associated with significantly greater loss of renal function and a higher risk of acute renal impairment among patients, and in this study, the significant decrease in proteinuria among patients switching from TDF + 3TC + EFV to BIC/FTC/TAF also indicated that BIC/FTC/TAF presented better safety and protection of renal functions compared with TDF-based regimens.

This study also evaluated blood lipid levels within 48 weeks after receiving BIC/FTC/TAF treatment. After ART-naïve PWHs received BIC/FTC/TAF, serum lipid panels, including TG, TC, LDL and HDL levels, increased significantly at week 24 and kept stable levels at week 48, while in ART-experienced patients, lipid panel presented upward trends among PWH switching from TDF + 3TC + EFV, which was consistent with previous report^[24], which indicated that periodic monitoring lipid panels was necessary among PWH taking BIC/FTC/TAF, especially within 24 weeks after the initiation of ART. In addition, previous studies demonstrated that^[24], compared with TAF, the TDF-based antiretroviral regimen has a stabilizing effect on blood lipids in treatment-naive patients. We found that after switching from a TDF-based ARV regimen to BIC (bictegravir), blood lipids increased within 24 weeks but reached a stable level 48 weeks after initiation, which was consistent with the results of previous studies^[24–25].

In ART-experienced PWHs who switched from EVG/c/FTC/TAF, LDL-C decreased significantly at 24 and 48 weeks, which may be related to the discontinuation of cobicistat (a cytochrome P450 3A4 inhibitor), which was associated with increased blood lipid levels^[26], and after switching to BIC/FTC/TAF, the LDL-C level improved, providing a basis for lipid management in the regimen switch of ART-experienced patients^[17].

In ART-experienced patients, 7 (17.9%) patients presented a viral load > 10,000 copies/ml, and resistance test indicated that NNRTI and 3TC resistance. 48-week after switching to BIC/FTC/TAF, the VL of all patients was completely inhibited, which indicated virological success and the effectiveness of antiviral therapy. This result demonstrated that BIC/FTC/TAF, as an ARV regimen with a high genetic barrier, can efficiently suppress HIV with mutation points in NNRTI and 3TC ^[26] in the real world.

The limitations presented in this study. Firstly,the study was a small-sample ones which may affect the statistical power. Secondly,the follow-up time (48 weeks) was comparatively short, and the long-time impact of BIC/FTC/TAF should be further evaluated. Finally, this study was a retrospective single-center study rather than prospective one ,and potential bias existed in the study.In general, the conclusions of this study needed to be further verified in multi-center studies with a larger sample size.

This study provided valuable evidence for the protective effects of BIC/FTC/TAF as a first-line regimen for ART-naive or -experienced patients with early or mild renal injury. We found that, among these patients with proteinuria, after taking BIC/FTC/TAF regimen, the levels of urinary protein decreased significantly, and renal function keep stable at 48-week of initiation, which provided valuable clinical evidence for the renal protective effect of BIC/FTC/TAF. In ART-naive patients with early or mild renal impairment, blood lipid levels increased significantly during the first 24 weeks, and thereafter kept stable levels. With those switching from EVG/c/FTC/TAF (cobicistat-boosted) exhibiting significant LDL-C reduction. This result reveals the necessity of monitoring blood lipids in PWH receiving BIC/FTC/TAF, especially within 24 weeks after the initiation of ART.

ART

antiretroviral therapy

ARVs

antiretroviral drugs

ACR

urine albumin/creatinine

ANOVA

analysis of variance

BIC/FTC/TAF

bictegravir/emtricitabine/tenofovir alafenamide

CKD

chronic kidney disease

EVG/c/FTC/TAF

elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide

HIV

Human Immunodeficiency Virus

HIVAN

HIV-associated nephropathy

HDL

high-density lipoprotein cholesterol

LDL

low-density lipoprotein cholesterol

NNRTI

Non-nucleoside reverse transcriptase inhibitor

PWH

people with HIV

TDF

tenofovir disoproxil fumarate

TFV

tenofovir

TAF

tenofovir alafenamide

TC

total cholesterol

TG

triglycerides

TDF + 3TC + EFV

tenofovir disoproxil fumarate/lamivudine /efavirenz

UPQ

urinary protein quantification

UMA

urinary microalbumin

UP/C

urinary protein/creatinine

VL

viral load

α1-MG

α1-microglobulin

β2-MG

β2-microglobulin

Ethics approval and consent to participate

The study involving human participants was reviewed and approved by Human Science Ethical Committee of Beijing Ditan Hospital, Capital Medical University. Written informed consent for participation was not required for this study in accordance with the institutional requirements due to a retrospective study.

Consent for publication

Not applicable

Competing interests

The authors declared that they have no competing interests.

Funding

Support for this work was provided by: 1) Investigator-Initiated trial Program of the Internal Research Fund, Beijing Ditan Hospital, Capital Medical University(DTIIT202501); 2) Collaboration, Consistency, and Innovation Program of the National Center for Infectious Diseases (Beijing)༈GCST20250101); 3) the Capital health development scientific research project (2024-1G-3013); 4) Special Program for Clinical Research and Scientific Innovation Transformation (KCZL2025XX)

Author Contribution

Conceived and designed the experiments: Hongxin Zhao & Jiang Xiao; Performed experiment: Yining Zhao. Wrote the manuscript: Yining Zhao. Collected and analyzed the data: Yining Zhao, qinlan Li, Liangxi Zhu, Chengyu Gao, Jialu Li

Acknowledgements

We acknowledged the work of statisticians for their statistical analysis in Ditan Hospital.

Data Availability

The datasets used and/or studied during the current study are available from the Beijing Ditan Hospital, Capital Medical University, Beijing, China.

World Health Organization (WHO). https://www.who.int/
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Table.1 Baseline characteristic

	ART-naive (n=266)	ART-experienced (n=39)
Age (years)	36 ± 11	40 ± 15
Male,n (%)	259 (97.3%)	37 (94.9%)
Baseline CD4 T cells^*(cells/µL)	360.16 (202~488)	551.55 (355.75~738.5)
Baseline CD8 T cells^*(cells/µL)	1189.01 (715~1487)	1111.18 (658.25~1340.5)
VL>10000 (coppies/ml)n(%)	174 (65.4%)	7 (17.9%)
UREA^*(mmol/L)	4.69(3.87~5.42)	4.82(4.07~5.31)
Cr^*(mmol/L)	75.04(55.15~81.83)	77.46(67.10~85.70)
eGFR^*(ml/min/1.73m²)	113.98(105.85~123.73)	107.67(98.40~120.70)
≥90 n (%)	247 (92.9%)	32 (82.0%)
60-89 n (%)	19 (7.1%)	7(18.0%)
ACR^*(mg/mmol) n (%)
<3	159 (97.4%)	39(100%)
3-30	7 (2.6%)	0
UP/C^*(mg/mmol)	2.97(1.43~3.48)	4.33(2.31~5.72)
UPQ^*(mg/dl)	21.66(10.50~22.65)	33.02(18.30~42.40)
>14 n (%)	174(65.41%)	30(76.92%)
UMA^*(mg/l)	44.77(14.85~44.08)	83.22(44.00~105.30)
>25 n (%)	150(56.39%)	29(74.36%)
α1-MG^*(mg/l)	16.04(0~19.43)	20.82(17.40~24.40)
>6 n (%)	180(67.67%)	34(87.18%)
β2-MG^*(mg/l)	1.26 (0.39~1.26)	1.70(1.59~1.67)
>0.3 n (%)	234(89.97%)	36(92.31%)
TC^*(mmol/L)	4.16 (3.58~4.66)	4.29 (3.90~5.07)
TG^*(mmol/L)	1.33(0.80~1.56)	1.75(0.58~1.18)
HDL^*(mmol/L)	0.98(0.83~1.11)	1.00 (0.77~2.74)
LDL^*(mmol/L)	2.60 (2.14~2.95)	2.66 (0.89~1.29)

No competing interests reported.

Efficacy and protective effects of urinary biomarkers among people with HIV with early or mild renal injury taking Bictegravir/Emtricitabine/Tenofovir Alafenamide (BIC/FTC/TAF): a real world study in China

Status:

Version 1

Abstract

Objective

Methods

Results

Conclusion

Figures

Introduction

Methods

Ethical consideration

Study population

Clinical data collection

Clinical definition

Assessment of changes in renal functions and lipid panel

Assessment of efficacy and safety

Statistical analysis

Result

Baseline characteristics

Renal safety

Changes in Lipid metabolism

Efficacy

Assessment of adverse effects

Discussion

Conclusion

Abbreviations

Declarations

Competing interests

Funding

Author Contribution

Acknowledgements

Data Availability

References

Tables

Additional Declarations

Status:

Version 1