Real-life data of immune recovery using bictegravir/emtricitabine/tenofovir alafenamide in virologically suppressed people living with HIV. Results at 48-96†weeks of RETROBIC Study.

BACKGROUND: Switching strategy with bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) has become a gold standard for people living with HIV (PLWH), achieving high efficacy and safety rates. However, data regarding immune status in long-term real-life cohorts of pretreated patients are needed. METHODS: We performed a multicentre, non-controlled, retrospective study in virologically suppressed PLWH switching to B/F/TAF. We evaluated CD4+, CD8+ and CD4+/CD8+ ratio, efficacy and safety at weeks 48 and 96. RESULTS: The study comprised 1966 PLWH from 12 hospitals in Spain, of whom 80% were men, and the median age was 51.0 [42.0-57.0] years. The median time of HIV infection was 18.0 [10.0-27.0] years. No significant changes in CD4+, CD8+ T cells, or CD4+/CD8+ were observed after 96 weeks. Nevertheless, in women at weeks 48 and 96, we found a significant increase of CD4+ T cells and a significant decrease in CD8+ T cells. In patients ≥60 years at week 96, CD4 T cells significantly increased and CD8+ T cells significantly decreased at week 48. The on-treatment analysis revealed HIV-RNA <50 copies/mL in 95.6% (1700/1779) and 96.7% (1312/1356) of patients at weeks 48 and 96, respectively. The rates increased to 99.2% (1765/1779) and 99.7% (1352/1356) when considering HIV-RNA <200 copies/mL. No resistance mutations were detected in virologic failures. B/F/TAF discontinuations accounted for 10.2% (200). Simplification was the most common reason for discontinuation in 3.8% (74) of patients. CONCLUSION: In long-term virologically controlled PLWH, B/F/TAF achieved high efficacy rates and slightly improved immune status in women and individuals aged 60 and over after 48 and 96 of switching.

Effect of single-administration of D-sorbitol pretreatment on the bitterness and continued willingness to take asenapine: a randomized, single-blind, placebo-controlled, crossover trial.

BACKGROUND: Asenapine has unique orally-related side effects, such as a bitter taste induced by sublingual administration, which often results in discontinuation of the medication. While the FDA has approved black-cherry-flavored asenapine, several countries have prescribed only unflavored versions. Specifically, Asians commonly report experiencing the bitterness of asenapine because they are more sensitive to bitter tastes than other ethnic groups. In this study, with the aim of improving adherence by reducing the bitterness of asenapine, we investigated the effects of D-sorbitol, which reduced the bitterness parameters of taste sensors in our previous basic study on the bitterness and continuity of asenapine among patients with schizophrenia. METHODS: Twenty adult patients with schizophrenia were included in this single-blind, placebo-controlled, crossover trial. Participants rinsed their mouths with single-administration of D-sorbitol or a placebo prior to each administration of asenapine. We then conducted the questionnaires and assessed changes in the bitterness of asenapine (primary end point) and willingness to continue its use (secondary end point). RESULTS: D-sorbitol significantly improved the bitterness of asenapine (p = 0.038). Although it did not significantly increase the willingness to continue asenapine (p = 0.180), it did show improvement over the placebo in enhancing willingness to continue, especially in patients who were not accustomed to its taste. CONCLUSION: Our findings indicate that single-administration of D-sorbitol significantly reduces the bitterness of asenapine. In countries where flavored asenapine is not available, this finding could benefit patients who were not accustomed to its bitter taste. TRIAL REGISTRATION: This study was registered in the Japan Registry of Clinical Trials (jRCTs041210019) on May 14, 2021.

Bictegravir/Emtricitabine/Tenofovir Alafenamide in a Multicentre Cohort: Real-Life Experience From Spain.

BACKGROUND: The evaluation of bictegravir, emtricitabine, and tenofovir alafenamide (BIC/FTC/TAF) in clinical trials has shown high rates of virological suppression but information about its use in real-life settings is scarce. OBJECTIVE: To evaluate the effectiveness, safety, durability, and predictive variables of therapeutic failure of BIC/FTC/TAF in a real-life cohort. METHODS: This observational, retrospective, multicentered cohort study included treatment-naive (TN) and treatment-experienced (TE) adult patients living with HIV (PLWH) who started treatment with BIC/FTC/TAF from January 1, 2019, to January 31, 2022. Treatment effectiveness (based on intention-to-treat [ITT], modified ITT [mITT], and on-treatment [OT]), tolerability, and safety were evaluated in all patients who started BIC/FTC/TAF antiretroviral therapy. RESULTS: We included a total of 505 PLWH of whom 79 (16.6%) were TN and 426 (83.4%) were TE. Patients were followed up for a median (interquartile range [IQR]) of 19.6 (9.6-27.3) months, and 76% and 56% of PLWH reached month 6 and month 12 of treatment, respectively. Rates of TN PLWH with HIV-RNA <50 copies/mL in the OT, mITT, and ITT groups were 94%, 80%, and 62%, respectively, after 12 months of BIC/FTC/TAF treatment. Rates of TE PLWH with HIV-RNA <50 copies/mL were 91%, 88%, and 75% at month 12. The multivariate analysis revealed that neither age, sex, CD4 cell count <200 cells/µL, or viral load >100 000 copies/mL were associated with therapeutic failure. CONCLUSION AND RELEVANCE: Our real-life data showed that BIC/FTC/TAF is effective and safe for use in the treatment of both TN and TE patients in clinical practice.

Rapid ART initiation with bictegravir/emtricitabine/tenofovir alafenamide in individuals presenting with advanced HIV disease (Rainbow study).

BACKGROUND: A rapid ART initiation approach can be beneficial in people with advanced HIV disease, in consideration of their high morbidity and mortality. The aim of our study was to evaluate the feasibility, efficacy and safety of rapid ART start with BIC/FTC/TAF in this setting. METHODS: Pilot, single-centre, single-arm, prospective, phase IV clinical trial conducted in a tertiary Italian hospital. Thirty ART-naïve people presenting with advanced HIV-1 diagnosis (defined as the presence of an AIDS-defining event and/or CD4 cell count <200 µL), were enrolled. Main exclusion criteria were active tuberculosis, cryptococcosis and pregnant/breastfeeding women. BIC/FTC/TAF was started within 7 days from HIV diagnosis. The primary endpoint was clinical or virologic failure (VF). Immunological parameters, safety, feasibility, neurocognitive performances and patient-reported outcomes were assessed as well. RESULTS: Over the study period, 40 (34%) of 116 patients diagnosed with HIV infection at INMI Spallanzani had advanced disease, of whom 30 (26%) were enrolled. The proportion of participants with HIV-RNA <50 cp/mL was 9/30 (30%) at week (w) 4, 19/30 (63%) at w12, 24/30 (80%) at w24, 23/30 (77%) at w36 and 27/30 (90%) at w48. Two unconfirmed VF occurred. No ART discontinuation due to toxicity or VF was observed. No ART modification was performed based on the review of genotype and no mutations for the study drugs were detected. Mean CD4 cells count changed by 133 cells/µL at BL to 309 cells/µL at w 48 and 83% of participants had a CD4 > 200 cells/µL at w 48. Two participants developed IRIS and one was diagnosed with disseminated TB and needed an ART switch. INTERPRETATIONS: Our results support the feasibility, efficacy and safety of BIC/FTC/TAF as a rapid ART strategy in patients with advanced HIV disease.

Health-related quality of life in patients aged 6-18 years with chronic hepatitis C treated with sofosbuvir/velpatasvir.

BACKGROUND & AIMS: The aim of this study was to assess the effect of treatment with sofosbuvir/velpatasvir (SOF/VEL) on the health-related quality of life (HRQL) of children with chronic hepatitis C. METHODS: In the non-commercial, non-randomized, open-label PANDAA-PED study, 50 children aged 6-18 years with chronic hepatitis C were treated with a fixed dose of SOF/VEL. All patients achieved sustained virologic response 12 weeks after the end of treatment (SVR12). Evaluation of HRQL was performed twice: at baseline (before the treatment) and during the SVR12 analysis using the KIDSCREEN-27 questionnaires, which included 5 dimensions of HRQL, for child self-reporting and parent proxy reporting. The normal range for the population was set to T values of 50 ± 10 points. Child-parent agreement was analysed using the intra-class correlation coefficient (ICC) and Bland-Altman test. RESULTS: Mean T values were within the normal range for all dimensions, both before and after treatment. There was a significant improvement in physical well-being based on the children's self-assessment (from 48.53 to 51.21, p = .03). In addition, a trend towards better scores in the 'social support & peers' part of the parent proxy evaluation (from 45.98 to 48.66, p = .06) was noticed. After the treatment, the proportion of children self-assessing their physical well-being as below normal significantly decreased from 17% to 5% (p = .007). HRQL scores were not associated with patients' sex, but in most cases, younger age correlated with better HRQL. Evaluation of the ICC for child self-reports versus parent proxy reports revealed poor to moderate agreement for most single measures. Bland-Altman analysis showed that in all dimensions, both before and after treatment, the limits of agreement (LoAs) exceeded ±5 points (half of the SD and considered a maximum allowed difference). CONCLUSIONS: A significant proportion of children with chronic hepatitis C have decreased HRQL in all dimensions, but effective treatment with SOF/VEL leads to an improvement in some areas of well-being. As the effect of HCV on HRQL is more pronounced in older patients, treatment of younger children should be indicated to prevent them from experiencing decreased HRQL due to ongoing HCV infection in the future.

Effectiveness, durability and safety of dolutegravir and lamivudine versus bictegravir, emtricitabine and tenofovir alafenamide in a real-world cohort of HIV-infected adults.

OBJECTIVE: Dolutegravir plus lamivudine (2-DR) is suggested as an initial and switch option in HIV-1 treatment. The aim of this study was to analyze the effectiveness, durability, and safety of 2-DR compared to bictegravir/emtricitabine/tenofovir alafenamide (3-DR). PATIENTS AND METHODS: This was an observational, ambispective study that included all treatment-naïve (TN) and treatment-experienced (TE) people living with HIV/AIDS (PLWH), who started 2-DR or 3-DR between 01 July 2018, and 31 January 2022. The primary endpoint was non-inferiority, at 24 and 48 weeks, of 2-DR vs 3-DR regarding the percentage of PLWH with viral load (VL)<50 and 200 copies/mL in TN (12% margin) and VL≥50 and 200 copies/mL in TE (4% margin). Durability of response and safety were also measured. RESULTS: 292 PLWH were included (39 TN and 253 TE). In TN PLWH, non-inferiority was not achieved at 24 weeks (17; 95% CI -17 to 51 p = 0.348). By week 48, all PLWH on 3-DR maintained VL<50 copies/mL compared to 70% of PLWH on 2-DR although without reaching statistical significance (-33; 95% CI -60 to -10 p = 0.289). Non-inferiority was not achieved in TE PLWH either at 24 (0.4; 95% CI -9 to 10 p = 1) or at 48 weeks (4.5; 95% CI -0.5 to 9 p = 0.132). In TN, the risk of treatment discontinuation was similar between groups (HR: 0.31, p = 0.07); similar rates were also found in TE (HR: 1.3, p = 0.38). TE PLWH on 2-DR showed a better safety profile compared to 3-DR (p = 0.017). CONCLUSION: Our results did not show non-inferiority in terms of virological effectiveness. Additionally, durability and safety of 2-DR were confirmed to be similar to 3-DR.

Predicting Factors of Plasma HIV RNA Undetectability after Switching to Co-Formulated Bictegravir, Emtricitabine, and Tenofovir Alafenamide in Experienced HIV-1 Patients: A Multicenter Study.

Switching to bictegravir, emtricitabine, and tenofovir alafenamide (BIC/FTC/TAF) from other antiretroviral regimens is safe and effective for virologically suppressed people living with HIV (PLWH). The term virological suppression includes both low but detectable HIV viremia and undetectable HIV viremia, and the latter is possibly associated with a lower immune activation state. Herein, we describe a 24-month follow-up of experienced PLWH with plasma HIV RNA undetectable or detectable < 50 copies/ml switching to BIC/FTC/TAF. A previous 12-month monitoring was available, and the factors correlated with treatment efficacy. This retrospective multicenter study included PLWH who switched to BIC/FTC/TAF in the period of 2019-2022, and who were HBsAg and HCV RNA negative. The follow-up study times were 6 (T6), 12 (T12), 18 (T18), and 24 (T24) months after the switch (T0). Survival analysis with multiple-failure-per-subject design, Kaplan-Meier survival estimates, multivariate analysis of variance, multilevel linear regression, and a hierarchical ordered logistic model were applied. A total of 329 PLWH had plasma HIV RNA which was either undetectable or detectable at <50 copies/mL at T0, and 197 responded to all inclusion criteria: M/F 140/57; the median CD4+ cell count was 677 cells/mm3; and HIV RNA at T0 was undetectable in 108 patients. Most of the 197 patients (122, 61.9%) were on a previous INSTI-based regimen. HIV RNA undetectability was more frequent at each follow-up point in patients with HIV RNA that was undetectable at T0, and it showed a higher frequency throughout the follow-up period in patients with always-undetectable HIV RNA in the 12 months before the switch. A higher nadir CD4 cell count had a predictive role, and HBcAb positivity had no influence. In conclusion, the switch could be programmed and possibly delayed on a case-by-case basis in order to achieve persistent plasma HIV RNA undetectability. Undiagnosed loss of HBcAb has no detrimental consequences on the response to BIC/FTC/TAF.

Treatment-emergent reverse transcriptase resistance during antiretroviral therapy with bictegravir, tenofovir alafenamide, and emtricitabine: A case series.

OBJECTIVES: Bictegravir/tenofovir alafenamide/emtricitabine (BIC/TAF/FTC) is a complete regimen for the treatment of HIV with a high barrier to resistance and few reported cases of treatment failure. We present three cases of treatment-emergent resistance to nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) in patients with suboptimal treatment adherence and assess whether the resistance-associated mutations were present before BIC/TAF/FTC initiation or emerged during therapy. METHODS: We used genotypic drug resistance testing by Sanger sequencing to identify emergent resistance mutations in plasma viral load specimens collected after combination antiretroviral therapy initiation in all participants. Additionally, we performed ultra-deep sequencing by Illumina MiSeq on the earliest available plasma HIV-1 viral load specimen and on any available specimens closest in time to the initiation of BIC/TAF/FTC therapy to identify low-abundance resistance mutations present in the viral quasispecies. RESULTS: All three participants developed NRTI resistance after prolonged exposure and incomplete adherence to BIC/TAF/FTC. The T69N, K70E, M184I, and/or T215I mutations identified in clinical samples at the time of virological failure were not present on deep sequencing of either baseline samples or samples collected before BIC/TAF/FTC initiation. CONCLUSIONS: Despite a generally high genetic barrier to resistance, NRTI resistance-associated mutations may emerge during therapy with BIC/TAF/FTC in the setting of suboptimal adherence.

Lumateperone for the Treatment of Schizophrenia: Number Needed to Treat, Number Needed to Harm, and Likelihood to Be Helped or Harmed.

Objective: To describe lumateperone for the treatment of schizophrenia in adults using number needed to treat (NNT), number needed to harm (NNH), and likelihood to be helped or harmed (LHH).Methods: Data were obtained from the 3 phase 2/3 lumateperone trials, conducted between 2011 and 2016, in patients with schizophrenia diagnosed using the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision, or Fifth Edition. Efficacy was assessed using various response criteria; tolerability was principally assessed using rates of adverse events (AEs).Results: Pooled data of the 2 informative studies showed statistically significant estimates of NNT versus placebo for lumateperone 42 mg/d for the responder thresholds of ≥ 20% and ≥ 30% improvement on Positive and Negative Syndrome Scale (PANSS) total scores, with NNT for response versus placebo at 4 weeks and endpoint of 9 (95% confidence interval [CI], 5-36) and 8 (95% CI, 5-21), respectively. Pooling all studies, discontinuation because of AEs was uncommon, and the NNH versus placebo was 389 (not statistically significant from placebo [NS]). Rates of individual AEs resulted in NNH versus placebo > 10 except for somnolence/sedation (NNH of 8; 95% CI, 6-12). The occurrence of weight gain ≥ 7% from baseline yielded a NNH estimate of 122 (NS). Rates of akathisia were lower for patients receiving lumateperone compared with placebo. LHH for response versus somnolence/sedation was ~ 1 for lumateperone (similar to the risperidone active control group); otherwise, lumateperone exhibited LHH ratios that were much greater than 1 for all other AEs and that ranged from 13.6 to 48.6 for these other benefit-risk calculations.Conclusions: In 3 phase 2/3 trials, the benefit-risk assessment of lumateperone was favorable as measured by NNT, NNH, and LHH.Trial Registration: ClinicalTrials.gov identifiers: NCT01499563, NCT02282761, NCT02469155.

Patient-reported outcomes among virally suppressed people living with HIV after switching to Co-formulated bictegravir, emtricitabine and tenofovir alafenamide.

BACKGROUND: While some evidence has suggested the benefits of co-formulated bictegravir, emtricitabine and tenofovir alafenamide (B/F/TAF) in improving the quality of life of people living with HIV (PLWH), patient-reported outcome studies that focus on Asian population remain scarce. We aimed to determine the changes in HIV-related symptom burden in virally-suppressed PLWH switching to B/F/TAF in a real-world setting. METHODS: PLWH on stable antiretroviral therapy (ART) for ≥6 months with plasma HIV RNA <200 copies/mL who decided to switch to B/F/TAF were eligible for the study. Participants' experience with 20 symptoms were assessed using HIV Symptom Index at baseline and weeks 24 and 48. Responses were dichotomized in two ways: 1) present vs. not present; and 2) bothersome vs. not bothersome, and compared across time points. RESULTS: Six hundred and thirty participants (prior regimen, 94.4% integrase inhibitor-based) who completed week 48 visit were included in the analysis. Forty-eight weeks after switching to B/F/TAF, six symptoms were significantly less prevalent, and seven symptoms were significantly less bothersome. Improvement was more pronounced in participants whose prior regimen was elvitegravir-based versus dolutegravir-based. Logistic regression results showed that prior dolutegravir-based ART and pre-existing diabetes independently predicted improvement in diarrhea/loose bowels and muscle aches/joint pain, respectively. Despite the overall improvement, some symptoms persisted in a substantial proportion of participants. CONCLUSIONS: Virally-suppressed PLWH might benefit from a regimen switch to B/F/TAF to reduce the prevalence and level of bother of HIV-related symptoms. Nevertheless, additional multidisciplinary interventions are warranted to further alleviate the symptom burden of PLWH.

Same-day initiation of bictegravir/emtricitabine/tenofovir alafenamide: Week 48 results of the FAST study-IMEA 055.

BACKGROUND: Initiating same-day ART for newly HIV-diagnosed individuals reduces secondary HIV transmissions and the risk of them being lost to follow-up between diagnosis and initiation of ART. METHODS: The FAST study was a national, prospective, single-arm study assessing the efficacy, safety and feasibility of bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) in a same-day initiation model. ART had to be started on the first medical appointment, before any laboratory results were available. Participants completed a self-administered questionnaire at each visit including a HIV anxiety 5-point Likert scale. The primary outcome was the proportion of participants in the ITT population with plasma HIV RNA (pVL) < 50 copies/mL at Week (W) 24 using the FDA Snapshot algorithm. RESULTS: Overall, 112 participants were included in the ITT population. During follow-up, seven participants discontinued the study drug but remained on the study, and seven others discontinued follow-up. According to FDA Snapshot analysis, at W24 and W48, 90/112, (80.4%; 95% CI: 71.8-87.3) and 95/112 (84.8%; 95% CI: 76.8-90.9) of participants achieved pVL < 50 copies/mL, respectively. The protocol-defined virological failure (PDVF, 2 consecutive pVL ≥ 50 copies/mL as of W24) was observed in 11/112 (9.8%) at W24 and 14/112 (12.5%) at W48. No emergent resistance-associated mutation was detected in those with PDVF at W24 and W48. BIC/FTC/TAF was well tolerated through to W48, with a low incidence of grade 3-4 adverse events (15/100 person-years). Patient opinion of same-day treatment initiation and continuing BIC/FTC/TAF was very favourable. CONCLUSIONS: These results suggest that BIC/FTC/TAF is safe, effective and well accepted for same-day initiation.

A possible case of bictegravir-associated severe unconjugated hyperbilirubinemia.

BACKGROUND: Bictegravir (BIC) co-formulated with emtricitabine (FTC) and tenofovir alafenamide (TAF) is approved by Federal Food and Drug Administration in 2018 for both treatment-naïve and experienced persons living with HIV (PLWH). CASE PRESENTATION: A young man with recently diagnosed human immunodeficiency virus (HIV) infection presented with jaundice. Blood work was significant for mild anemia and grade 4 unconjugated hyperbilirubinemia. A comprehensive evaluation for hemolytic anemia failed to reveal any etiology. Other causes of hyperbilirubinemia were negative. Four months prior, patient was started on antiretroviral therapy with a single tablet regimen containing bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF), brand name Biktarvy®, and the medication was suspected to be the cause. The medication was held, and the hyperbilirubinemia improved. CONCLUSION: Severe hyperbilirubinemia can be found in the patient using BIC/FTC/TAF. The data for this adverse reaction is scarce, and more studies are needed on this possible side effect. The mechanism of unconjugated hyperbilirubinemia by INSTI remains undefined.

Early post-liver transplant use of direct-acting antivirals in naive and NS5A inhibitor-experienced HCV patients.

Direct-acting antiviral drugs (DAA) are safe and effective in the HCV population. However, in patients with decompensated cirrhosis and/or active hepatocellular carcinoma or relapse to NS5A inhibitors, response rates are lower and DAA therapy must be postponed until after liver transplant in an era of organ shortage and suboptimal donors. We aimed to assess the prevalence of patients still HCV infected at time of transplantation over the last 3 years in our Center and describe the safety and efficacy of DAA therapy started as soon as possible after surgery. We enrolled all HCV viraemic patients transplanted in our Centre from January 2019 to March 2022. The follow-up was closed in July 2022. Among 490 liver transplants, 49 (10%) patients were still HCV viraemic at operation, 43 naive to DAA and 6 were NS5A-experienced. Median donor age was 64 years; donor risk index was 1.8. In naive patients, sofosbuvir/velpatasvir was started after a median time of 1 day from surgery, while in NS5A-experienced sofosbuvir/velpatasvir/voxilaprevir after 14.5 days (p = .001). Response rate was 98%. 1 NS5A-experienced patient experienced acute cholestatic hepatitis which promptly reverted after permanent DAA discontinuation. Hence, very early post-liver transplant HCV eradication was safe and effective thanks to a close teamwork which involved anaesthesiologists, transplant surgeons and hepatologists.

Switching to coformulated bictegravir, emtricitabine, and tenofovir alafenamide maintained viral suppression in adults with historical virological failures and K65N/R mutation.

OBJECTIVES: Real-world experience with coformulated bictegravir, emtricitabine, and tenofovir alafenamide (BIC/FTC/TAF) is sparse as a switch regimen among people living with HIV (PLWH) having achieved viral suppression after previous virologic failures with the emergence of K65N/R. METHODS: In this retrospective study, PLWH aged ≥20 years who had previous virologic failures with emergent K65N/R were included for switching to BIC/FTC/TAF after having achieved plasma HIV RNA load (PVL) <200 copies/ml for ≥3 months. PLWH were excluded if integrase inhibitor resistance-associated mutations were detected. The primary end point was losing virologic control (PVL >50 copies/ml) at week 48 using a modified US Food and Drug Administration snapshot algorithm. RESULTS: A total of 72 PLWH with K65N/R who switched to BIC/FTC/TAF were identified. A total of 42 (59.7%) had concurrent M184V/I, and 9 (12.5%) had ≥1 thymidine analog mutations. The median duration of viral suppression was 4.7 years (interquartile range 2.3-5.8), and 97.2% (n = 70) had PVL <50 copies/ml before switching. After a median observation of 98.6 weeks (interquartile range 77.9-120.3), 94.4% (n = 68) continued BIC/FTC/TAF. At week 48, the rate of losing virologic control was 2.8% (2/72). M184V/I was not associated with viral rebound. CONCLUSION: Despite the emergence of K65N/R +/- M184V/I after virologic failures, BIC/FTC/TAF could be an option for simplification after viral suppression.

Comparison of the design and methodology of Phase 3 clinical trials of bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) and dolutegravir-based dual therapy (DTG) in HIV: a systematic review of the literature.

INTRODUCTION: Current recommended antiretroviral regimens include a combination of two (dual; DT) or three (triple; TT) antiretroviral drugs. This study aims to determine whether the quality of evidence from clinical trials of dolutegravir (dolutegravir/lamivudine [DTG/3TC] or dolutegravir/rilpivirine [DTG/RPV]) is methodologically comparable to that of clinical trials conducted with bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF). AREAS COVERED: A systematic review of the medical literature was carried out in PubMed without date or language restrictions, following the PRISMA guidelines. All aspects of the methodological design of phase 3 randomized clinical trials (RCTs) of DT and TT, evaluated by the European Medicines Agency (registration trials), were reviewed. The quality of clinical trials was assessed using the Jadad scale. EXPERT OPINION: The search identified 5, 3 and 2 phase 3 RCTs with BIC/FTC/TAF, DTG/3TC and DTG/RPV, respectively, that met the inclusion criteria. The designs would not be comparable due to differences in pre-randomization losses, blinding, patient recruitment, as well as differences in methodological quality, with the average score of the RCTs conducted with BIC/FTC/TAF, DTG/3TC and DTG/RPV being 4.2 (high quality), 3.0 (medium quality) and 3.0 (medium quality), respectively. Due to methodological differences between the BIC/FTC/TAF, DTG/3TC and DTG/RPV RCTs, the results of these are not comparable.

Utilization of bictegravir/emtricitabine/tenofovir alafenamide in patients with end-stage renal disease on hemodialysis.

PURPOSE: The combination antiretroviral bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) is a single-tablet, once-daily regimen used in individuals living with HIV; however, its use in the context of renal impairment is uncertain. We report 6 patient cases of BIC/FTC/TAF utilization in individuals with HIV with end-stage renal disease (ESRD) requiring long-term hemodialysis (HD). SUMMARY: These case reports describe the utilization of BIC/FTC/TAF in individuals with HIV who require chronic HD, the laboratory parameters measured, and patient-reported quality of life and adverse events. CONCLUSION: Utilization of BIC/FTC/TAF appears to be an option for individuals with HIV who have ESRD and require long-term HD. This regimen allows for once-daily dosing, elimination of potential serious drug interactions, and simplified patient ART regimens in our patient subset.

Antitumor activity of lurbinectedin in combination with oral capecitabine in patients with metastatic breast cancer.

BACKGROUND: Preclinical studies showed a synergistic effect for 5-fluorouracil and lurbinectedin against solid tumors. This phase I trial evaluated a combination of capecitabine plus lurbinectedin in patients with selected advanced solid tumors. Results in patients with relapsed metastatic breast cancer (MBC) are described. PATIENTS AND METHODS: Patients received capecitabine daily on day (D)1-D14 combined with lurbinectedin on D1, D8 or D1 every 3 weeks (q3w) intravenously, following a standard 3 + 3 escalation design and expansion at the recommended dose (RD). RESULTS: Of the 81 enrolled patients, 28 had relapsed MBC: 20 with hormone receptor (HR)-positive tumors and 8 with triple-negative tumors; 3 treated in the D1,D8 schedule and 25 in the D1 schedule. The RD was capecitabine 1650 mg/m2 daily on D1-D14 plus lurbinectedin 2.2 mg/m2 on D1 q3w. Sixteen confirmed responses and two prolonged disease stabilizations (≥6 months) were observed [overall response rate (ORR)/clinical benefit rate (CBR) = 57%/64% at all dose levels; 47%/60% at the RD]. Twelve responses and both prolonged stabilizations occurred in HR-positive tumors (ORR/CBR = 60%/70% at all dose levels, 56%/78% at the RD). Four responses were found in triple-negative tumors (ORR and CBR = 50% at all dose levels; 33% at the RD). Myelotoxicity was reversible and manageable at the RD; most non-hematological toxicities were mild/moderate. No episodes of febrile neutropenia or severe palmar-plantar erythrodysesthesia syndrome occurred. No major pharmacokinetic drug-drug interaction was found between lurbinectedin, capecitabine or capecitabine metabolites. CONCLUSIONS: The capecitabine/lurbinectedin combination showed encouraging clinical activity in relapsed MBC, especially in HR-positive tumors. Toxicity was manageable at the RD. Further development is warranted in relapsed MBC.

Efficacy and Safety of Bictegravir-Based Regimen in Pregnant Women Living with HIV: A Case Report.

Bictegravir (BIC) is included in international guidelines as the first line of therapy for patients living with Human Immunodeficiency Virus (HIV), either as initial therapy or as a replacement for patients with prior antiretroviral therapy (ART). Due to limited efficacy and safety data, BIC is currently not recommended during pregnancy. Data on the safety and efficacy of BIC during pregnancy were unavailable at the time of drug approval. In our case, BIC/TAF/FTC was effective in suppressing viral load (VL) in pregnancy, and there were no reported safety issues for the mother or the baby.