- |||||||||| Prezista (darunavir) / J&J, Intelence (etravirine) / J&J
SAT009 : Management of highly treatment-experienced children, adolescents, and young adults experiencing treatment failure in sub-Saharan Africa (Plaza Level Auditorium/Channel 4) - May 5, 2023 - Abstract #IASHIV2023IAS_HIV_23;
An overview of patient characteristics, prevalence of drug resistance mutations, and viral suppression after initiation on DRV and/or ETR will be shared, along with case studies highlighting different national models for improving the care of highly treatment-experienced young people. A panel of experts will lead a discussion on how to detect treatment failure, sequence ART regimens, and the next steps needed to improve the quality of life for these priority populations.
- |||||||||| Symtuza (darunavir/cobicistat/emtricitabine/tenofovir alafenamide) / J&J, Gilead, Prezista (darunavir) / J&J, Biktarvy (bictegravir/emtricitabine/tenofovir alafenamide) / Gilead
Enrollment closed, Trial completion date, Trial primary completion date: BIC-T&T: Efficacy of BIC/F/TAF Versus Standard of Care in the Treatment of New HIV Infection Diagnoses in the Context of 'Test and Treat' (clinicaltrials.gov) - Apr 19, 2023
P3, N=36, Active, not recruiting,
Our study may also be used as pipeline to search and design new potential inhibitors of HIV-1 proteases. Recruiting --> Active, not recruiting | Trial completion date: Jul 2022 --> Jul 2023 | Trial primary completion date: Jul 2022 --> Jul 2023
- |||||||||| Prezista (darunavir) / J&J
Journal: Selection of HIV-1 for resistance to fifth generation protease inhibitors reveals two independent pathways to high-level resistance. (Pubmed Central) - Apr 4, 2023
Darunavir (DRV) is exceptional among potent HIV-1 protease inhibitors (PIs) in high drug concentrations that are achieved in vivo...Viral variants from the two pathways showed differential selection of compensatory mutations in Gag cleavage sites. These results reveal the high level of selective pressure that is attainable with fifth generation PIs, and how features of the inhibitor affect both the resistance pathway and the residual potency in the face of resistance.
- |||||||||| Symtuza (darunavir/cobicistat/emtricitabine/tenofovir alafenamide) / J&J, Gilead, Prezista (darunavir) / J&J
Journal: Darunavir/cobicistat/emtricitabine/tenofovir alafenamide in treatment-na (Pubmed Central) - Mar 14, 2023
Using various statistical tests, the results revealed that the immune response is normal in both groups, but with a statistically significant difference (p D/C/F/TAF may be a suitable treatment option for individuals with HIV-1 and NPCs.
- |||||||||| Prezista (darunavir) / J&J, Opsumit (macitentan) / Nippon Shinyaku, J&J
The Effect of Treatment Discontinuation Definitions on Estimates of Treatment Persistence () - Mar 9, 2023 - Abstract #ISPOR2023ISPOR_483;
Estimates of treatment duration in real-world data vary substantially depending on the applied statistical methods and rules of gap filling and discontinuation. We recommend conducting sensitivity analyses of underlying assumptions and methods, and the consideration of scenario planning to ensure that medication consumption forecasts are robust and consistent.
- |||||||||| Review, Journal: Promising Repurposed Antiviral Molecules to Combat SARS-CoV-2: A Review. (Pubmed Central) - Mar 3, 2023
To understand the virology of SARS-CoV-2, potential therapeutic approaches for the treatment of COVID-19 disease, synthetic methods of potent drug candidates, and their mechanisms of action have been addressed in this review. It intends to help readers approach the accessible statistics on the helpful treatment strategies for COVID-19 disease and to serve as a valuable resource for future research in this area.
- |||||||||| Prezista (darunavir) / J&J, Isentress (raltegravir) / Merck (MSD)
Journal: Antiretroviral Levels in the Cerebrospinal Fluid: The Effect of Inflammation and Genetic Variants. (Pubmed Central) - Jan 22, 2023
At bi-variate analysis, several associations, including the effect of BBBi (emtricitabine, raltegravir), age (zidovudine and darunavir), and high CSF neopterin (NRTIs and border-line for PIs) were suggested...At multivariate analysis age, gender, BMI, and altered BBB were independent predictors of nucleoside reverse transcriptase CSF concentrations; age (for protease inhibitors) and body mass index and altered BBB (integrase strand transfer inhibitors) were also associated with ARV CSF exposure. We describe factors associated with CSF concentrations, showing that demographic, BBB integrity and, partially, genetic factors may be predictors of drug passage in the central nervous system.
- |||||||||| Prezista (darunavir) / J&J, Olumiant (baricitinib) / Incyte, Eli Lilly
Journal: Multi-Targeting Approach in Selection of Potential Molecule for COVID-19 Treatment. (Pubmed Central) - Jan 22, 2023
The MM-GBSA, IFD, and MD simulation studies imply that the drug nintedanib has the highest binding stability among the shortlisted. Nintedanib, primarily used for idiopathic pulmonary fibrosis, can be considered for repurposing for us against COVID-19.
- |||||||||| Prezista (darunavir) / J&J
Review, Journal: Darunavir ethanolate: Repurposing an anti-HIV drug in COVID-19 treatment. (Pubmed Central) - Dec 29, 2022
In COVID-19, the difficulties of proper analysis of current pre-clinical/clinical data as well as the creation of new evidence concerning drug repurposing will be crucial. The current manuscript aims to evaluate the repurposing of an anti-HIV drug Darunavir Ethanolate in COVID-19 treatment with in silico study and we discuss the therapeutic progress of Darunavir Etanolate, to prevent SARS-CoV-2 replication, which supports its clinical assessment for COVID-19 therapy.
- |||||||||| Enrollment closed, Enrollment change: HERV-K Suppression Using Antiretroviral Therapy in Volunteers With Amyotrophic Lateral Sclerosis (ALS) (clinicaltrials.gov) - Dec 27, 2022
P1, N=122, Active, not recruiting,
Hence, it is concluded that darunavir, moxalactam and eprosartan may be considered as potential inhibitors of LDHA and can be used for cancer therapy after proper validation of their effectiveness through in vitro, in vivo and clinical trials.Communicated by Ramaswamy H. Sarma. Recruiting --> Active, not recruiting | N=200 --> 122
- |||||||||| Prezista (darunavir) / J&J
Journal: Identification of Darunavir Derivatives for Inhibition of SARS-CoV-2 3CL. (Pubmed Central) - Dec 24, 2022
Importantly, 29# and 50# exhibited a similar activity against the protease in Omicron variants. The inhibitory effect of compounds 29# and 50# on the SARS-CoV-2 3CL warrants that they are worth being the template to design functionally improved inhibitors for the treatment of COVID-19.
- |||||||||| Prezista (darunavir) / J&J
Journal: Antiretroviral protease inhibitors induce features of cellular senescence that are reversible upon drug removal. (Pubmed Central) - Dec 22, 2022
Given how these features disappeared with drug removal, certain features of senescence may not be prognostic as defined by an irreversible growth arrest. Importantly, for patients that are treated or have been treated with ATV/r, our data suggest that switching to another PI that does not promote premature aging conditions (DRN/r) may improve the associated age-related complications.
- |||||||||| Prezista (darunavir) / J&J
Journal: Identification, Isolation, and Structural Characterization of Novel Forced Degradation Products of Darunavir Using Advanced Analytical Techniques Like UPLC-MS, Prep-HPLC, HRMS, NMR, and FT-IR Spectroscopy. (Pubmed Central) - Dec 20, 2022
Hence, the present study focused on using High-Resolution Mass, 1D, and 2D H, C NMR data for concrete confirmation of structures for degradation products. The online version contains supplementary material available at 10.1007/s10337-022-04226-z.
- |||||||||| Prezista (darunavir) / J&J, Paxlovid (nirmatrelvir and ritonavir) / Pfizer, Lagevrio (molnupiravir) / Ridgeback Biotherap, Merck (MSD)
Journal: The exploration of phytocompounds theoretically combats SARS-CoV-2 pandemic against virus entry, viral replication and immune evasion. (Pubmed Central) - Dec 6, 2022
However, the greater burden of ARC among older PLHIV, most of which are established dementia risk factors, warrants the establishment of commensurate prevention strategies and greater attention to neurocognitive screening. Taken altogether, these results shed a light on that phytocompounds have a therapeutic potential for the treatment of anti-SARS-CoV-2 may base on multi-target effects or cocktail formulation for blocking viral infection through invasion/activation, transcription/reproduction, and posttranslational cleavage to battle COVID-19 pandemic.
- |||||||||| Prezista (darunavir) / J&J
Journal: Molecular Dynamics Study on Selected Bioactive Phytochemicals as Potential Inhibitors of HIV-1 Subtype C Protease. (Pubmed Central) - Nov 25, 2022
Of the eight compounds (CMG, MA, UA, CA, BA, UAA, OAA and OA) evaluated, only six (CMG (-9.9 kcal/mol), MA (-9.3 kcal/mol), CA (-9.0 kcal/mol), BA (-8.3 kcal/mol), UAA (-8.5 kcal/mol), and OA (-8.6 kcal/mol)) showed favourable activities against HIVpro and binding landscapes like the reference FDA-approved drugs, Lopinavir (LPV) and Darunavir (DRV), with CMG and MA having the highest binding affinities...Overall, this is the first computational report on the anti-HIV-1 activities of CMG and MA, with efforts on their in vitro and in vivo evaluations underway. Judging by the binding affinity, the degree of stability, and compactness of the lead metabolites (CMG, MA, CA, BA, OA, and UAA), they could be concomitantly explored with conventional HIVpro inhibitors in enhancing their therapeutic activities against the HIV-1 serotype.
- |||||||||| Prezista (darunavir) / J&J, Tivicay (dolutegravir) / ViiV Healthcare
Enrollment closed, Enrollment change: Body Composition Sub-study of the D2EFT Trial (clinicaltrials.gov) - Nov 25, 2022
P4, N=155, Active, not recruiting,
Judging by the binding affinity, the degree of stability, and compactness of the lead metabolites (CMG, MA, CA, BA, OA, and UAA), they could be concomitantly explored with conventional HIVpro inhibitors in enhancing their therapeutic activities against the HIV-1 serotype. Recruiting --> Active, not recruiting | N=300 --> 155
- |||||||||| cyclosporin A microemulsion / Generic mfg., etodolac / Generic mfg.
PK/PD data, Preclinical, Journal: Dual Delivery of Cyclosporin A and Etodolac Using Polymeric Nanocapsules in a Rabbit Eye Model: Ocular Biodistribution and Pharmacokinetic Study. (Pubmed Central) - Nov 16, 2022
Despite molecular size and structural differences, both CsA and Edc after liberation from nanocapsule drops can permeate into the tissues of the anterior as well as posterior segments of the eye. The biodistribution and pharmacokinetic data might help and strengthen our understanding of synergetic anti-inflammatory activity of CsA and Edc from nanocapsules after its ocular topical application for managing keratoconjunctivitis sicca.
- |||||||||| Prezista (darunavir) / J&J, Invirase (saquinavir) / Roche, Crixivan (indinavir sulfate) / Merck (MSD)
Journal: HIV protease inhibitor attenuated astrocyte autophagy involvement in inflammation via p38 MAPK pathway. (Pubmed Central) - Nov 15, 2022
In the following study, we verified the results from RNA-sequence using the liquid chip technique, qRT-PCR, Elisa, and western blots, which suggested that LPV induced inflammatory response and the p38 MAPK pathway was involved in this process. Collectively, we demonstrated that PIs attenuated the involvement of astrocyte autophagy in inflammation via the p38 MAPK pathway, providing new insights into the mechanism of HAND.
- |||||||||| Tybost (cobicistat) / Gilead, Prezista (darunavir) / J&J
Review, Journal: SARS-CoV-2 Infection-Of Music and Mechanics of Its Spikes! A Perspective. (Pubmed Central) - Nov 15, 2022
In this Perspective, we discuss the various evidential findings of virus propagation and connect them to respective underpinning cellular biomechanical states leading to corresponding manifestations of the viral activity. We further propose avenues to tackle the virus, including from a "musical" vantage point, and contain its relentless strides that are currently afflicting the global populace.
- |||||||||| Prezista (darunavir) / J&J
Journal: Organic solvents aggregating and shaping structural folding of protein, a case study of the protease enzyme. (Pubmed Central) - Nov 12, 2022
In molecular dynamic simulations (MDS), the complex of the protease enzyme with Darunavirwas found highly stable in urea aqueous solution compared to when with the ethylene glycol (EG) or glycerol solvents...On the contrary lack of such clustering in urea solvent, the protease showed conventional structural folding in the presence or absence of the drug molecule. These novel findings may help to better understand the protease enzymes, which could be controlled by deep eutectic solvents.
- |||||||||| Review, Journal: Interactions of Antiretroviral Drugs with Food, Beverages, Dietary Supplements, and Alcohol: A Systematic Review and Meta-analyses. (Pubmed Central) - Nov 2, 2022
Didanosine, zalcitabine, zidovudine, efavirenz, amprenavir, fosamprenavir, and indinavir should be taken on an empty stomach for maximum patient benefit...There is insufficient evidence available to make recommendations about consuming juice or alcohol with antiretroviral drugs. Resolving drug-food interactions may contribute to maximized cART effectiveness and safety.
- |||||||||| Journal: Discovery of Novel HIV Protease Inhibitors Using Modern Computational Techniques. (Pubmed Central) - Oct 28, 2022
HPS/002 and HPS/004 have been found to be most promising in terms of IC/percent inhibition (90.15%) of HIV-1 PR, in addition to their drug metabolism and safety profile. These hit candidates should be investigated further as possible HIV-1 PIs with improved efficacy and low toxicity through in vitro experiments and clinical trial investigations.
- |||||||||| Prezista (darunavir) / J&J
Review, Journal: Beyond darunavir: recent development of next generation HIV-1 protease inhibitors to combat drug resistance. (Pubmed Central) - Oct 25, 2022
We highlight here our molecular design strategies to promote backbone hydrogen bonding interactions to combat drug-resistance and specific design of polycyclic ether templates to mimic peptide-like bonds in the HIV-1 protease active site. Our medicinal chemistry and drug development efforts led to the development of new generation inhibitors significantly improved over darunavir and displaying unprecedented antiviral activity against multidrug-resistant HIV-1 variants.
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