- |||||||||| bictegravir (GS-9883) / Gilead
[VIRTUAL] INTEGRASE INHIBITORS TARGET MITOCHONDRIA IN BROWN ADIPOCYTES DISRUPTING THERMOGENESIS () - Mar 18, 2021 - Abstract #CROI2021CROI_725;
In in vitro models, InSTI exposure had opposite effects on the differentiation of white and brown fat. In brown adipocytes, the inhibition of brown thermogenic function by DTG was associated with interruption of mitochondrial proteins (e.g. COX IV and UCP1), which may be mediated through estrogen receptor.
- |||||||||| bictegravir (GS-9883) / Gilead
[VIRTUAL] EVALUATION OF COMBINATIONS OF CLINICAL INTEGRASE MUTATIONS ON InSTI RESISTANCE () - Mar 18, 2021 - Abstract #CROI2021CROI_641;
Chimeric viruses were grown in a reporter CD4+ T-cell line in the presence of 0.01-1,000nM raltegravir (RAL), elvitegravir (EVG), dolutegravir (DTG), cabotegravir (CAB), and bictegravir (BIC), where infection was measured by imaging cytometry. High-level resistance to DTG, CAB and BIC requires multiple integrase substitutions including compensatory mutations.
- |||||||||| bictegravir (GS-9883) / Gilead
[VIRTUAL] IN SILICO PREDICTION OF MONTHLY BICTEGRAVIR MICRONEEDLE ARRAY PATCHES () - Mar 18, 2021 - Abstract #CROI2021CROI_585;
The PBPK model identified suitable dose and release rate strategies with practical patch sizes for QMT MAP administration of BIC. These simulations support the case for long-acting BIC MAPs and the data can inform strategies to address the technological challenges in the development of this alternative drug delivery system for antiretroviral therapy.
- |||||||||| bictegravir (GS-9883) / Gilead, Pifeltro (doravirine) / Merck (MSD)
[VIRTUAL] TOTAL AND UNBOUND DORAVIRINE CONCENTRATIONS AND VIRAL SUPPRESSION IN CSF OF HIV+ PTS () - Mar 18, 2021 - Abstract #CROI2021CROI_566;
Most patients switched from InSTI based regimens [Bictegravir (5); Dolutegravir (4) and Elvitegravir (3)]. Total and unbound trough DORA concentrations in CSF exceeded the EC50 value against WT virus (5.1 ng/mL) by 11.4 and 8.7-fold respectively, suggesting that DOR given in combination with FTC/TAF may contribute to inhibit viral replication in this compartment.
- |||||||||| bictegravir (GS-9883) / Gilead
[VIRTUAL] BICTEGRAVIR CONCENTRATIONS AND VIROLOGIC RESPONSES IN PLWH RECEIVING 1HP FOR LTBI () - Mar 18, 2021 - Abstract #CROI2021CROI_321;
We aimed to assess the completion rate, bictegravir (BIC) trough concentration, cytokine profile, and virologic response in PLWH with LTBI who received 1HP and BIC/FTC/TAF concurrently. BIC concentrations were significantly decreased with concurrent use of 1HP among PLWH with LTBI.
- |||||||||| bictegravir (GS-9883) / Gilead, Tivicay (dolutegravir) / ViiV Healthcare
Biomarker, New trial: Gut Microbiota, PGx and INSTIs Response (clinicaltrials.gov) - Mar 17, 2021
P, N=200, Recruiting,
- |||||||||| bictegravir (GS-9883) / Gilead, Actemra IV (tocilizumab) / Roche, JW Pharma
Review, Journal: Drug Repurposing Strategy (DRS): Emerging Approach to Identify Potential Therapeutics for Treatment of Novel Coronavirus Infection. (Pubmed Central) - Mar 16, 2021
The methodologies involved in drug repurposing can be categorized into three groups such as drug-oriented, target-oriented and disease or therapy-oriented depending on the information available related to quality and quantity of the physico-chemical, biological, pharmacological, toxicological and pharmacokinetic property of drug molecules. This review focuses on drug repurposing strategy applied for existing drugs including Remdesivir, Favipiravir, Ribavirin, Baraticinib, Tocilizumab, Chloroquine, Hydroxychloroquine, Prulifloxacin, Carfilzomib, Bictegravir, Nelfinavir, Tegobuvir and Glucocorticoids etc to determine their effectiveness toward the treatment of COVID-19.
- |||||||||| bictegravir (GS-9883) / Gilead
Journal: Long Dissociation of Bictegravir from HIV-1 Integrase-DNA Complexes. (Pubmed Central) - Mar 3, 2021
BIC also had a longer t and maintained longer antiviral activity after drug washout than DTG with the clinically relevant resistance IN mutant G140S+Q148H. Structural analyses indicate that BIC makes more contacts with the IN-DNA complex than DTG mainly via its bicyclic ring system which may contribute to more prolonged residence time and resilience against many resistance mutations.
- |||||||||| Vocabria (cabotegravir oral) / ViiV Healthcare, bictegravir (GS-9883) / Gilead, Pifeltro (doravirine) / Merck (MSD)
Preclinical, Journal: Development and validation of a multiplex UHPLC-MS/MS assay with stable isotopic internal standards for the monitoring of the plasma concentrations of the antiretroviral drugs bictegravir, cabotegravir, doravirine, and rilpivirine in people living with HIV. (Pubmed Central) - Feb 27, 2021
This bioassay was fully validated following international guidelines and achieved good performances in terms of trueness (94.7%-107.5%), repeatability (2.6%-11%), and intermediate precision (3.0%-11.2%) over the clinically relevant concentration ranges (from 30 to 9000 ng/mL for bictegravir, cabotegravir, and doravirine and from 10 to 1800 ng/mL for rilpivirine). This sensitive, accurate, and rapid UHPLC-MS/MS assay is currently applied in our laboratory for routine therapeutic drug monitoring of the oral drugs bictegravir and doravirine and is also intended to be applied for the monitoring of cabotegravir/rilpivirine levels in plasma from PLWH receiving once monthly or every 2-month intramuscular injection of these long-acting antiretroviral drugs.
- |||||||||| bictegravir (GS-9883) / Gilead
Journal: Fulminant diffuse cerebral toxoplasmosis as the first manifestation of HIV infection. (Pubmed Central) - Feb 23, 2021
Dexamethasone was initiated and he developed rigours...He was then initiated on Biktarvy 50 mg/200 mg/25 mg, one tablet daily, which contains 50 mg of bictegravir, 200 mg of emtricitabine and tenofovir alafenamide fumarate equivalent to 25 mg of tenofovir alafenamide...This case highlights missed opportunities to request HIV serology and raises awareness that cerebral toxoplasmosis can occur as the first manifestation of HIV. Prompt diagnosis and early initiation of antiretroviral therapy reduces morbidity and mortality in this patient cohort.
- |||||||||| bictegravir (GS-9883) / Gilead
Journal: Screening, simulation, and optimization design of small molecule inhibitors of the SARS-CoV-2 spike glycoprotein. (Pubmed Central) - Feb 2, 2021
Based on the interactions among the drug molecules, the S protein and the amino acid environment around the binding sites, rational structure-based optimization was performed using the molecular connection method and bioisosterism strategy to obtain Ti-2, BD-2, and Ar-3, which have much stronger binding ability to the S protein than the original molecules. This study provides valuable clues for identifying S protein inhibitor binding sites and the mechanism of the anti-SARS-CoV-2 effect as well as useful inspiration and help for the discovery and optimization of small molecule S protein inhibitors.
- |||||||||| bictegravir (GS-9883) / Gilead
Clinical, Journal: Nothing is perfect: the safety issues of integrase inhibitor regimens. (Pubmed Central) - Jan 23, 2021
While this association and its clinical relevance are not clear, physicians should be alert to the appearance of the aforementioned AEs and others in the future. In the meantime, INSTIs continue to be the preferred option in guidelines on antiretroviral therapy.
- |||||||||| bictegravir (GS-9883) / Gilead, Tivicay (dolutegravir) / ViiV Healthcare
Clinical, Journal, Adverse events: Analysis of Pharmacovigilance Databases for Dolutegravir Safety in Pregnancy. (Pubmed Central) - Jan 8, 2021
Given widespread use of new antiretroviral drugs worldwide and anticipated use of new drugs, prospective follow-up of pregnant women and birth surveillance studies such as Tsepamo are critically needed.Neural tube defects have been reported among infants born from women taking a wide range of antiretrovirals in 4 pharmacovigilance databases. Safety reports were inconsistent between databases and very hard to interpret.
- |||||||||| bictegravir (GS-9883) / Gilead
Review, Journal, Adverse events: Update on Adverse Effects of HIV Integrase Inhibitors. (Pubmed Central) - Jan 3, 2021
This is worrying since patients from African descent are at higher risk of cardio-vascular events and increased body mass index (BMI) can cause further increase metabolic risk. There is possibly an additional effect of tenofovir alafenamide (TAF) on weight increase.Discrepancies between clinical trials - with low rates of adverse events - and reports from real-life settings might be due partly to under-representation of some groups of patients in clinical trials, and/or the short duration of follow-up, since some adverse effects may only occur after prolonged exposure.Preliminary data on safety of bictegravir (BIC), from clinical trials and non-trial settings, are very reassuring and seem to show lower rates of adverse events compared to DTG.Elvitegravir/cobicistat (EVG/cobi) need to be used with caution in patients with other co-morbidities given potential for polypharmacy, as it is the case for aging patients, because of the high potential of drug-drug interactions due to effects of the cobicistat booster.We are awaiting the release of cabotegravir (CAB), which could represent a good option for patients struggling with adherence, despite injection site reactions.Pharmacogenetics is a promising way to explore adverse effects occurrence in the INSTI class.
- |||||||||| bictegravir (GS-9883) / Gilead
[VIRTUAL] Cardiovascular and metabolic effects of anti-retroviral medications: a retrospective chart review () - Dec 26, 2020 - Abstract #ASHP2020ASHP_3686;
In particular, bictegravir is widely used but has very little published data in this area...Patient cohorts will be compared by the class of anti-retroviral medication initiated and effects will be adjusted for concomitant medications and lifestyle factors that may affect the primary outcomes. Regression analysis will determine the association between ART and resultant cardiovascular and metabolic risk factors.
- |||||||||| bictegravir (GS-9883) / Gilead
[VIRTUAL] Evaluation of the drug-drug interaction between metformin and bictegravir () - Dec 26, 2020 - Abstract #ASHP2020ASHP_3278;
No additional effect on HgbA1C was noted and appeared to be similar to an expected diabetes pharmacotherapy regimen response in PLWHIV. Prescribers should be aware of this potential interaction; however, no empiric MET TDD adjustment appears necessary when initiating MET-BIC concurrent therapy.
- |||||||||| bictegravir (GS-9883) / Gilead
[VIRTUAL] Impact of telehealth services in an HIV primary care clinic during COVID-19 () - Dec 26, 2020 - Abstract #ASHP2020ASHP_2775;
Viral load suppression rates and undetectable viral status were maintained in PLWH. Utilization of telehealth services is a useful approach which allows healthcare providers, nurses and clinical pharmacists the ability to provide remote services without jeopardizing patient outcomes.
- |||||||||| bictegravir (GS-9883) / Gilead, Pifeltro (doravirine) / Merck (MSD), Tivicay (dolutegravir) / ViiV Healthcare
[VIRTUAL] Dolutegravir/Doravirine: A dual-therapy, nucleoside/nucleotide reverse transcriptase inhibitor (NRTI) sparing HIV antiretroviral regimen in a patient with declining renal function () - Dec 26, 2020 - Abstract #ASHP2020ASHP_2590;
The patient was prescribed a regimen of efavirenz/tenofovir DF/emtricitabine (Atripla) upon referral to the specialty clinic. On his first visit he was initiated on bictegravir/tenofovir alafenamide/emtricitabine (Biktarvy) but was switched to a regimen consisting of doravirine 100mg, dolutegravir 50mg, and lamivudine 50mg in January of 2019 because of his declining kidney function...The patient was on esomeprazole, a PPI, for management of severe GERD with esophageal damage (Schatzki’s ring), thus ruling out Juluca as an option...As of February 2020, his CD4 count was 707 and as of June 2020, the patient’s viral loads have remained consistently suppressed at 12 months on a two-drug combination of doravirine and dolutegravir.
- |||||||||| bictegravir (GS-9883) / Gilead
PK/PD data, Journal: Pharmacokinetics of Co-encapsulated Antiretrovirals with Ingestible Sensors. (Pubmed Central) - Dec 18, 2020
To assess the safety and impact, if any, coencapsulation might have on ARV concentrations, we evaluated the pharmacokinetics of ARVs coencapsulated with an ingestible sensor for eight commonly used fixed-dose combination ARVs: emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF); FTC/tenofovir alafenamide (TAF); efavirenz (EFV)/FTC/TDF; abacavir (ABC)/lamivudine (3TC); dolutegravir (DTG)/ABC/3TC; rilpivirine (RPV)/TAF/FTC; elvitegravir (EVG)/cobicistat (COBI)/FTC/TAF; and bictegravir (BIC)/FTC/TAF...In a subsequent evaluation of FTC/TDF and BIC/FTC/TAF using a crossover design, the geometric mean ratio (GMR) between the coencapsulated and the unencapsulated formulations for FTC/TDF were the following: FTC, 84.6% (90% confidence interval [CI] 66.6-107.4) for AUC and 77.5% (60.1-99.9) for Cmax...The observed deviation in FTC/TDF (Truvada) may be due to participant characteristics, fasted/fed conditions, and/or random variation and may warrant further investigations with a larger sample size. These findings provide assurance for use of co-encapsulated ARVs for future HIV treatment-adherence research.
- |||||||||| bictegravir (GS-9883) / Gilead
Journal: Synthesis, biological evaluation and in silico modeling of novel integrase strand transfer inhibitors (INSTIs). (Pubmed Central) - Nov 2, 2020
Both molecules were very stable in human liver microsomes and plasma, demonstrated high affinity towards plasma proteins and did not show cytochrome (CYP) inhibition. This benefit profile indicates the great potential of these molecules as attractive candidates for subsequent evaluation as oral long-acting drugs and long-acting nanosuspension formulations for intramuscular injection.
- |||||||||| bictegravir (GS-9883) / Gilead
[VIRTUAL] METHODS FOR SCREENING AND MONITORING BY GBM MASTER REGULATORY GENE MARKERS IN LIQUID BIOPSY () - Oct 24, 2020 - Abstract #SNO2020SNO_774;
RESULTSWe characterized 10 MR genes in GSC with ≥1 GC-rich promoter region that is hypomethylated and accessible (ATACseq) in GBM/GSC per GSE70175/92460/52271 (19 samples) and GSE67633/96088 (14 samples), and hypermethylated and inaccessible in lymphocytes/PBMC per GSE98837 (6) and GSE74912 (13), respectively...Conclusions Chromosomal accessibility of MR and signal amplification in MRGN of GSC provide powerful substrates for a non-NGS, low-cost, liquid-based GBM detection system with potentially high sensitivity and specificity. Further testing and optimization are ongoing.
- |||||||||| bictegravir (GS-9883) / Gilead
[VIRTUAL] RAPID ONSET MILIARY TB: A MANIFESTATION OF IMMUNE RECONSTITUTION INFLAMMATORY SYNDROME () - Oct 12, 2020 - Abstract #CHEST2020CHEST_1107;
Paradoxical tuberculosis immune reconstitution inflammatory syndrome (TB-IRIS) is an early complication of antiretroviral therapy in patients with TB, that results from the rapid restoration of immune function, with a consequent exaggerated immune response, causing an exacerbation of pre-existing infections, or the unmasking of subclinical infections. Patients with risk factors, such as immigration, should be monitored closed following the initiation of ART, for the manifestation of previously subclinical infections, such as TB.
- |||||||||| bictegravir (GS-9883) / Gilead
Phase classification: Study to Evaluate Safety, Pharmacokinetics, and Antiviral Activity of Bictegravir (GS-9883) in Human Immunodeficiency Virus (HIV)-1 Infected Participants (clinicaltrials.gov) - Oct 7, 2020
P1b, N=23, Completed,
Patients with risk factors, such as immigration, should be monitored closed following the initiation of ART, for the manifestation of previously subclinical infections, such as TB. Phase classification: P1 --> P1b
- |||||||||| bictegravir (GS-9883) / Gilead, Tivicay (dolutegravir) / ViiV Healthcare, Isentress (raltegravir) / Merck (MSD)
[VIRTUAL] Differential effects of raltegravir, dolutegravir and bictegravir on human adipocytes () - Sep 21, 2020 - Abstract #HIVGlasgow2020HIV-Glasgow_231;
However, dolutegravir and raltegravir show alterations in adiponectin expression, which does not occur with bictegravir. Further studies are necessary to ascertain the pathophysiological relevance of these findings with respect to the effects of INSTI‐containing treatments on body weight and metabolism in people living with HIV.
- |||||||||| bictegravir (GS-9883) / Gilead
[VIRTUAL] HLH Associated With Hepatitis B and HIV Co-Infection With Resultant Liver Failure () - Sep 15, 2020 - Abstract #ACG2020ACG_2816;
However, transfusion requirements and pyrexia returned, and he was started on etoposide per HLH-94 protocol resulting in significant clinical improvement and hospital discharge...Our patient’s HLH was most likely secondary to his active hepatitis B infection, as his viral load increased 25-fold, likely inciting the aberrant immune response. To our knowledge, this is the first reported case of HLH attributed to Hepatitis B with HIV co-infection.
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