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Introduction Methods Results Conclusion Treatment for people with HIV‐1 and end‐stage kidney disease (ESKD) on haemodialysis (HD) has previously required complex dose‐adjusted regimens, with limited data on the use of a single‐tablet regimen in this population. Our aim was to assess the efficacy and safety of once‐daily bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) and to evaluate the pharmacokinetics of bictegravir (BIC) in adults with HIV‐1 and ESKD on HD.We performed an open‐label extension (OLE) of an open‐label, multicentre, single‐group phase 3b study (NCT02600819) of adults with ESKD on HD and HIV‐1 with virological suppression. Participants switched to elvitegravir/cobicistat/F/TAF (E/C/F/TAF) 150/150/200/10 mg for 96 weeks, following which a subgroup of US participants entered an OLE phase in which they switched to B/F/TAF 50/200/25 mg for 48 weeks, returning for study visits at weeks 4 and 12, and every 12 weeks thereafter. Study assessments included virological response, safety and pharmacokinetic analysis of BIC.Ten participants entered the OLE (median age, 55 years). Virological suppression (HIV‐1 RNA <50 copies/mL) was maintained in all participants over 48 weeks of B/F/TAF treatment. B/F/TAF was well tolerated, with no treatment discontinuations. Mean BIC trough concentrations were lower than those previously reported for people with HIV‐1 with normal kidney function, but remained four‐ to seven‐fold higher than the established protein‐adjusted 95% effective concentration against wild‐type HIV‐1.These findings support the use of the once‐daily B/F/TAF single‐tablet regimen for people with HIV‐1 and ESKD on HD. This regimen offers a convenient treatment option for this population as it reduces the need for dose adjustment, eases pill burden and avoids potential drug–drug interactions associated with alternatives that may impact individuals on multiple medications or awaiting transplantation. [ABSTRACT FROM AUTHOR]

Background: Studies on switching to tenofovir alafenamide (TAF)‐based regimens raise concerns about a worse metabolic profile in people with HIV, even though most received tenofovir disoproxil fumarate (TDF) in their previous regimen. This study aims to evaluate changes in lipid fractions, glucose, and serum markers for hepatic steatosis (HS) after switching from a TDF‐ or TAF‐sparing regimen to bictegravir/emtricitabine/TAF (B/F/TAF). Methods: We performed a retrospective cohort study of people with HIV who switched to B/F/TAF from TDF‐ or TAF‐sparing regimens between January 2019 and May 2022 with at least 6 months of follow‐up. The primary endpoint was the absolute change in lipid fractions at 6 months. Secondary outcomes were changes in lipid fractions at 12 months and changes in other metabolic parameters (glucose, creatinine, and HS based on the triglyceride‐to‐glucose [TyG] ratio at 6 and 12 months). Changes were analysed using mixed linear regression models with random intercept and time as a fixed effect. Results: The study included 259 people with HIV (median age 55 [interquartile range (IQR) 47–60] years; 80% male; 88% Caucasian; CD4+ T‐cell count 675 [IQR 450–880] cells/mm3; 84.3% HIV‐RNA <50 copies/mL). In total, 63 patients (30%) had hypertension, 93 (44%) dyslipidaemia, 30 (14%) diabetes, and 45% obesity/overweight. Most (60%) switched from integrase inhibitor‐based regimens, and 21% switched from a boosted regimen. At 6 months, significant reductions were observed in total cholesterol (−7.64 mg/dL [95% confidence interval (CI) −13.52 to −1.76; p = 0.002]), triglycerides (−23.4 [95% CI −42.07 to −4.65]; p = 0.003), and TyG ratio (−0.14 [95% CI −0.23 to −0.05]; p < 0.001). Conclusion: In our real‐life cohort, the effect of switching TDF‐/TAF‐sparing regimens to triple therapy with B/F/TAF improved total cholesterol, triglycerides, and serum markers of HS at 6 months and was neutral for the remaining metabolic parameters at 12 months. [ABSTRACT FROM AUTHOR]

Background: Real‐world evidence is an essential component of evidence‐based medicine. The aim of the BICSTaR (BICtegravir Single Tablet Regimen) study is to assess effectiveness and safety of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in antiretroviral treatment‐naïve (TN) and treatment‐experienced (TE) people with HIV. Methods: BICSTaR is a prospective, observational cohort study. Participants (≥18 years) are being followed for 24 months. A pooled analysis is presented at 12 months, with the primary endpoint of effectiveness (HIV‐1 RNA <50 copies/mL) and secondary endpoints of safety and tolerability (as per protocol). An exploration of patient‐reported outcome measures using standardized questionnaires is included. Results: Between June 2018 and May 2021, 1552 people with HIV were enrolled across 12 countries. The analysed population comprised 1509 individuals (279 TN, 1230 TE); most were white (76%), male (84%) and had one or more comorbid conditions (68%). Median age was 47 years. After 12 months of B/F/TAF treatment, HIV‐1 RNA was <50 copies/mL in 94% (221/236) of TN participants and 97% (977/1008) of TE participants. Median CD4 cell count increased by 214 cells/μL (p < 0.001) in TN participants and 13 cells/μL (p = 0.014) in TE participants; median CD4/CD8 ratios increased by 0.30 and 0.03, respectively (both p < 0.001). Persistence was high at 12 months (TN, 97%; TE, 95%). No resistance to B/F/TAF emerged. Study drug‐related adverse events occurred in 13% of participants through 12 months, leading to B/F/TAF discontinuation in 6%. Conclusions: The findings of this study provide robust real‐world evidence to support the broad use of B/F/TAF in both TN and TE people with HIV. [ABSTRACT FROM AUTHOR]

Background: The aim of this randomized clinical trial (RCT) was to compare immunological changes in virally suppressed people living with HIV (PLWH) switching from a three-drug regimen (3DR) to a two-drug regimen (2DR). Methods: An open-label, prospective RCT enrolling PLWH receiving a 3DR who switched to bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) or dolutegravir/lamivudine (DTG/3TC) was performed. Blood was taken at baseline and months 6 and 12. The primary outcome was the change in CD4+ or CD8+ T-cell counts and CD4/CD8 ratio over time points. The secondary outcomes were the changes in immunological and inflammatory parameters. Parametric mixed-linear models with random intercepts and slopes were fitted separately for each marker after controlling for potential confounders. Results: Between the two arms (33 PLWH each), there was no difference in CD4+ or CD8+ T cells, CD4/CD8 ratio, and IL-6 trajectories. PLWH switching to DTG/3TC had increased levels of both transitional memory and terminally differentiated CD4+ T cells (arm-time interaction p-value = 0.02) and to a lesser extent for the corresponding CD8+ T-cell subsets (p = 0.09). Significantly lower levels of non-classical monocytes were detected in the B/F/TAF arm at T6 (diff = -6.7 cells/mm3; 95% CI; -16, +2.6; p-value for interaction between arm and time = 0.03). All differences were attenuated at T12. Conclusion: No evidence for a difference in absolute CD4+ and CD8+ T-cell counts, CD4/CD8 ratio, and IL-6 trajectories by study arm over 12 months was found. PLWH on DTG/3TC showed higher levels of terminally differentiated and exhausted CD4+ and CD8+ T lymphocytes and non-classical monocytes at T6. Further studies are warranted to better understand the clinical impact of our results. [ABSTRACT FROM AUTHOR]

The article discusses the efficacy of switching to bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in Black adults in the United States with HIV, including those with resistance and suboptimal adherence. The study aimed to address the underrepresentation of Black individuals in previous switch trials and found high levels of virologic suppression maintenance post-switch. The authors emphasized the importance of adherence and drug resistance analysis in interpreting the results, highlighting the forgiving nature of B/F/TAF and the need to consider resistance mutations to ensure treatment effectiveness. [Extracted from the article]

BackgroundThe aim of this randomized clinical trial (RCT) was to compare immunological changes in virally suppressed people living with HIV (PLWH) switching from a three-drug regimen (3DR) to a two-drug regimen (2DR).MethodsAn open-label, prospective RCT enrolling PLWH receiving a 3DR who switched to bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) or dolutegravir/lamivudine (DTG/3TC) was performed. Blood was taken at baseline and months 6 and 12. The primary outcome was the change in CD4+ or CD8+ T-cell counts and CD4/CD8 ratio over time points. The secondary outcomes were the changes in immunological and inflammatory parameters. Parametric mixed-linear models with random intercepts and slopes were fitted separately for each marker after controlling for potential confounders.ResultsBetween the two arms (33 PLWH each), there was no difference in CD4+ or CD8+ T cells, CD4/CD8 ratio, and IL-6 trajectories. PLWH switching to DTG/3TC had increased levels of both transitional memory and terminally differentiated CD4+ T cells (arm–time interaction p-value = 0.02) and to a lesser extent for the corresponding CD8+ T-cell subsets (p = 0.09). Significantly lower levels of non-classical monocytes were detected in the B/F/TAF arm at T6 (diff = −6.7 cells/mm3; 95% CI; −16, +2.6; p-value for interaction between arm and time = 0.03). All differences were attenuated at T12.ConclusionNo evidence for a difference in absolute CD4+ and CD8+ T-cell counts, CD4/CD8 ratio, and IL-6 trajectories by study arm over 12 months was found. PLWH on DTG/3TC showed higher levels of terminally differentiated and exhausted CD4+ and CD8+ T lymphocytes and non-classical monocytes at T6. Further studies are warranted to better understand the clinical impact of our results.Clinical Trial Registrationhttps://clinicaltrials.gov, identifier NCT04054089.

Background: forgiveness is the ability of a given regimen to maintain complete viral suppression despite a documented imperfect adherence. We explored forgiveness of bictegravir/emtricitabine/tenofovir alafenamide. Methods: drug refills were used to calculate the percent day covered (PDC) as a proxy of adherence. Forgiveness was calculated as the achieved rate of a selected HIV-RNA threshold by a given level of imperfect adherence. Results: 281 adult PLWH were followed for 343 patient/years. Adherence was very high with a median of 98% (IQR 95-100%). A PDC as low as 70% was sufficient to obtain 100% and maintain virologic suppression. According to probit analysis adherence was not related to the possibility to maintain an HIV-RNA TND or < 50 copies/ml. Conclusions: Long-term success of ART needs effective regimens that are the least intrusive of the patient's lifestyle, an elevated forgiveness may be considered as an additional feature that can further improve long-term outcomes. [ABSTRACT FROM AUTHOR]

This study aimed to explore the experiences of migrant people living with HIV (MLWH) enrolled in a Montreal-based multidisciplinary HIV care clinic with rapid antiretroviral treatment (ART) initiation and cost-covered ART. Between February 2020 and March 2022, 32 interviews were conducted with 16 MLWH at three time-points (16 after 1 week of ART initiation, 8 after 24 weeks, 8 after 48 weeks). Interviews were analyzed via the Framework Method. Thirty categories were identified, capturing experiences across the HIV care cascade. At diagnosis, most MLWH described "initially experiencing distress". At linkage, almost all MLWH discussed "navigating the health system with difficulty". At treatment initiation, almost all MLWH expressed "being satisfied with treatment", particularly due to a lack of side effects. Regarding care retention, all MLWH noted "facing psychosocial or health-related challenges beyond HIV". Regarding ART adherence, most MLWH expressed "being satisfied with treatment" with emphasis on their taking control of HIV. At viral suppression, MLWH mentioned "finding more peace of mind since becoming undetectable". Regarding their perceived health-related quality of life, most MLWH indicated "being helped by a supportive social network". Efficient, humanizing, and holistic approaches to care in a multidisciplinary setting, coupled with rapid and free ART initiation, seemed to help alleviate patients' concerns, address their bio-psycho-social challenges, encourage their initial and sustained engagement with HIV care and treatment, and ultimately contribute to positive experiences. [ABSTRACT FROM AUTHOR]

Abstract Background Currently recommended boosted protease-inhibitor (bPI) regimens may be associated with increased risk of cardiovascular or chronic kidney diseases; in addition, boosted regimens are particularly associated with drug-drug interactions. Since both cardiovascular and renal disease, and polypharmacy, are common in ageing people with HIV, there is a need for alternative efficacious regimens. bPI-based regimens are often the treatment of choice for individuals with pre-treatment or treatment-acquired resistance but it is plausible that carefully selected HIV-positive individuals with drug resistance, who are virologically suppressed on their current bPI regimen, could maintain virological efficacy when switched to bictegravir, emtricitabine and tenofovir alafenamide (B/F/TAF) fixed dose combination (FDC). Methods/design A phase IV, investigator-initiated, multicentre, open label pilot, randomised two-arm study to assess the safety and efficacy of switching from bPI regimen to B/F/TAF single tablet regimen in integrase inhibitor-naïve, virologically suppressed adults with HIV-1 infection harbouring drug resistance mutations. Eligible individuals will either continue on their bPI regimen or switch to B/F/TAF FDC. After 24 weeks, all participants in the bPI arm will be switched to B/F/TAF and followed for a further 24 weeks and all participants will be followed for 48 weeks. The primary efficacy endpoint is the proportion of participants with HIV-1 RNA

Background: Currently recommended boosted protease-inhibitor (bPI) regimens may be associated with increased risk of cardiovascular or chronic kidney diseases; in addition, boosted regimens are particularly associated with drug-drug interactions. Since both cardiovascular and renal disease, and polypharmacy, are common in ageing people with HIV, there is a need for alternative efficacious regimens. bPI-based regimens are often the treatment of choice for individuals with pre-treatment or treatment-acquired resistance but it is plausible that carefully selected HIV-positive individuals with drug resistance, who are virologically suppressed on their current bPI regimen, could maintain virological efficacy when switched to bictegravir, emtricitabine and tenofovir alafenamide (B/F/TAF) fixed dose combination (FDC).Methods/design: A phase IV, investigator-initiated, multicentre, open label pilot, randomised two-arm study to assess the safety and efficacy of switching from bPI regimen to B/F/TAF single tablet regimen in integrase inhibitor-naïve, virologically suppressed adults with HIV-1 infection harbouring drug resistance mutations. Eligible individuals will either continue on their bPI regimen or switch to B/F/TAF FDC. After 24 weeks, all participants in the bPI arm will be switched to B/F/TAF and followed for a further 24 weeks and all participants will be followed for 48 weeks. The primary efficacy endpoint is the proportion of participants with HIV-1 RNA < 50 copies/mL at week 24 using pure virologic response whilst the secondary efficacy endpoint is the proportion of participants with HIV-1 RNA < 50 copies/mL at Week 48. Other secondary outcome measures include between arm comparisons of drug resistance at virological failure, safety and tolerability and patient-reported outcome measures.Discussion: We aim to provide preliminary evidence of the efficacy of switching to B/F/TAF in patients with virological suppression on a bPI-based regimen who harbour select drug resistance mutations.Trial Registration: ISRCTN 44453201 , registered 19 June 2019 and EudraCT 2018-004732-30. [ABSTRACT FROM AUTHOR]

Introduction: BICSTaR (GS-EU-380-4472/GS-CA-380-4574/GS-IL-380- 5335) is an ongoing, multinational, observational cohort study evaluating real-world effectiveness and safety of B/F/TAF in ART naïve (TN) and ARTexperienced (TE) PLWH. Materials and Methods: This 12M pooled analysis included PLWH starting B/F/TAF in clinical practice from June 2018 to September 2020 (latterly during the COVID-19 pandemic) in Europe/Israel/Canada. Outcomes included virological effectiveness (HIV‐1 RNA <50 copies/ml [missing=excluded]), persistence, drug‐related adverse events (DRAEs), and laboratory parameters. Results: One-thousand one hundred thirty-five PLWH were included (Table 1). The TE group had older median age than TN. Of TE participants, 65%/20%/16% switched from INSTI/NNRTI/PI-based regimens (36% TDF/46% TAF/13% ABC); 12% had prior virologic failure. Baseline resistance was documented in 124/535 participants (NRTI/NNRTI/PI/ INSTI=6%/6%/3%/0.2%). Prevalence of comorbidities (47%/72% TN/TE) and concomitant medication usage was high. At 12M, 97% (149/154) of TN and 96% (771/800) of TE participants had HIV-1 RNA <50 copies/ml, and persistence on B/F/TAF was high [91% (1032/1135)]. In a multivariable analysis, TE participants with neuropsychiatric disorder ongoing at baseline had lower odds for viral suppression (odds ratio=0.45, 95% CI: 0.21-0.96). There was no emergence of resistance to the components of B/F/TAF. DRAEs occurred in 13% (148/1135) of participants; gastrointestinal and neuropsychiatric DRAEs were the most common (3% each). Discontinuations due to DRAEs were low (TN 4%; TE 6%). Serious DRAEs were rare (0.2%; 2 TE participants with depression). Lipidchanges are shown (Figure 1). Conclusion: B/F/TAF was associated with high levels of effectiveness and persistence after 12M in this large real-world cohort of TN and TE PLWH with a high comorbidity burden. Effectiveness was demonstrated across key subgroups (females, older participants, late presenters). Importantly, there were no new or unexpected safety findings. Collectively, these real-world data continue to support the use of B/F/TAF in clinical practice. [ABSTRACT FROM AUTHOR]

Introduction: BICSTaR is an ongoing, multinational, observational cohort study evaluating B/F/TAF in ART therapy-naïve (TN) and ART-experienced (TE) PLWH. The BICSTaR population has a high baseline prevalence of comorbidities (particularly neuropsychiatric). PROs were prospectively collected. Materials and Methods: One hundred eighty TN/955 TE participants were considered for the 12M analysis (cut-off Feb 2021, including people enrolled from Jun 2018 to Sept 2020, i.e. partially during the COVID19 pandemic). PRO measures: Adherence [visual analogue scale (VAS)]; physical/mental health [short form 36 (SF-36) questionnaire: Aggregated physical/mental component summary (PCS/MCS) scores; HIV-symptom index (HIV-SI; symptoms dichotomised into bothersome/not bothersome); HIV treatment satisfaction questionnaire (HIVTSQ; TE only); physician visits. VAS/SF-36/HIV-SI: Analysis population restricted to participants with questionnaires completed at both baseline/12M. SF-36/HIV-SI/HIVTSQ were described for participants with/without prior/ongoing neuropsychiatric comorbidities (TE only as TN subgroup was small). Results: Adherence to treatment was high at baseline (TE) and was maintained at 12M after switch to B/F/TAF [Table 1 (T1)]. Statistically significant improvements in PCS/MCS scores were observed in TN participants at 12M (p<0.05); scores remained stable in TE participants (Figure 1). The medyan (Q1, Q3) number of bothersome symptoms in TN participants declined from 6 (2, 9) at baseline to 2 (0, 6) at 12M (p<0.001; T1); TE, no change in absolute count. Statistically significant reductions in the frequency of several bothersome symptoms were reported in TN participants (p<0.05) (TE: No statistically significant changes). Treatment satisfaction was high at baseline (TE), with improvements observed at 12M following switch to B/F/TAF (p<0.001) (T1). Physician visits are shown (T1). In TE participants with baseline prior/ongoing neuropsychiatric comorbidities [275/955 (29%)], similar PRO trends were seen. Conclusion: In this real-world cohort of PLWH with a high prevalence of comorbidities (and in the setting of a global pandemic), patient-reported adherence, physical/mental health, bothersome symptoms, and treatment satisfaction were maintained/showed improvements during 12M of B/F/ TAF treatment. [ABSTRACT FROM AUTHOR]

Introduction: The ongoing observational BICSTaR study aims to demonstrate effectiveness, safety and tolerability of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in routine clinical practice in at least 1400 antiretroviral treatment (ART)-naive (TN) and ARTexperienced (TE) people living with HIV (PLHIV). Materials and Methods: This 12-month (12M) analysis of PLHIV receiving B/F/TAF in Europe and Canada assessed HIV 1-RNA (missing data=excluded analysis), drug-related (DR) adverse events (AEs), persistence and weight/body mass index (BMI) change. Results: At the time of data cut-off (March 2020), 513 participants (n=84 TN/n=429 TE) completed a 12M visit. Most were male (91%) and white (89%); the median age was 38 (TN) and 49 (TE) years. Prevalence of comorbidities at baseline was 76%; the most common were neuropsychiatric (28%), hyperlipidemia (18%) and hypertension (18%). 71%/18%/13% of TE participants switched from INSTI/NNRTI/PI-based regimens, respectively (26% TDF); 8% had a history of prior virologic failure. Baseline primary resistance prevalence by historical genotype was 9% [n=43/513; 5% had resistance mutations associated with NNRTIs, 3% PIs, 3% NRTIs (n=8 M184V/I, n=1 K65R) and 0.2% with INSTIs (n=1 G140S)]. At 12M, 100% of TN (n=74/74) and 96% (n=357/373) TE participants had viral load (VL) <50 copies/ml. Comparable and high effectiveness was observed in both male and female participants, including older individuals (Table 1). No major resistance substitutions to the components of B/F/TAF emerged. DRAEs occurred in 14% (n=12/84) of TN and 15% (n=64/429) of TE participants, with the most common being gastrointestinal (5%) and neuropsychiatric (4%); discontinuations due to DRAE were low (TN 3.6% and 7.2% TE) and 90% of study participants remained on B/F/TAF (n=462/513). Serious DRAEs were rare [0.4%; all in TE participants (n=2 depression)]. At 12M, median (Q1, Q3) weight change was +2.5 kg (0.5, 6.3) for TN (n=48) and +0.9 kg (-1.0, 3.0) for TE (n=269), with small changes in BMI of +0.8 kg/m² (0.1, 1.9) for TN and +0.3 kg/m² (-0.3, 1.0) for TE. Weight increase >10% was observed in 19% (n=9/48) and 5% (n=15/269) of TN and TE participants, respectively. Conclusion: The use of B/F/TAF in this real-world clinical cohort was associated with a high level of effectiveness and safety through 12M, inclusive of male, female and older PLHIV. [ABSTRACT FROM AUTHOR]