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Clinical, Journal: Single tablet HIV regimens facilitate virologic suppression and retention in care among treatment naïve patients. (Pubmed Central) - Oct 2, 2019 Overall, 622 patients started with an STR (100% efavirenz-based) and 406 with an MTR (65% atazanavir-based and 35% darunavir-based) regimen...There was no difference in the proportion of patients achieving at least 80% adherence, as measured by medication possession ratio (33.0% of STR patients and 30.1% of MTR patients; unadjusted OR 1.14; 95% CI 0.87-1.50; adjusted OR 1.04, CI 0.79-1.38). While it is difficult to eliminate confounding in this observational study, retention in care and virologic outcomes were better in patients prescribed STRs.
- |||||||||| Prezista (darunavir) / J&J, emtricitabine/tenofovir disoproxil fumarate / Generic mfg.
Clinical, Journal: Changes in plasma RANKL-osteoprotegerin in a Prospective, Randomized Clinical trial of Initial Antiviral Therapy: A5260s. (Pubmed Central) - Oct 2, 2019 While it is difficult to eliminate confounding in this observational study, retention in care and virologic outcomes were better in patients prescribed STRs. In virologically suppressed HIV-infected patients, the evolution of bone disease could be linked to plasma OPG levels; however the role of plasma levels of RANKL and RANKL/OPG ratio in the prediction of morbidity in treated HIV-1 infection may be limited.
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Journal: Prevalence of darunavir resistance in the United States from 2010 to 2017. (Pubmed Central) - Oct 2, 2019 Among the 4,799 samples with phenotypic resistance to one or more PIs, the proportions with phenotypic susceptibility to darunavir, atazanavir, and lopinavir were, respectively, 73.3%, 41.5%, and 46.0% in 2010 and 70.7%, 53.7%, and 48.8% in 2017. The prevalence of darunavir RAMs among commercially tested HIV-1 samples remained low and generally stable from 2010-2017, and high proportions showed phenotypic darunavir susceptibility.
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Journal: Sub-picomolar Inhibition of HIV-1 Protease with a Boronic Acid. (Pubmed Central) - Sep 28, 2019 Specifically, we find that replacing an aniline moiety in darunavir with a phenylboronic acid leads to 20-fold greater affinity for the protease...The BOH···OC hydrogen bonds between the boronic acid hydroxy group and Asp30 (or Asn30) of the protease are short ( r = 2.2 Å), and density functional theory analysis reveals a high degree of covalency. These data highlight the utility of boronic acids as versatile functional groups in the design of small-molecule ligands.
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Journal: Molecular dynamics and ligand docking of a hinge region variant of South African HIV-1 subtype C protease. (Pubmed Central) - Sep 20, 2019 The mutations affected the thermodynamic landscape of inhibitor binding as there were fewer observable chemical contacts between the N37T↑V variant protease and lopinavir, atazanavir and darunavir, respectively. These data elucidate the biophysical basis for the selection of hinge region insertion mutations by the HI virus.
- |||||||||| Prezista (darunavir) / J&J, Truvada (emtricitabine/tenofovir disoproxil fumarate) / Gilead, Isentress (raltegravir) / Merck (MSD)
Clinical, Journal: Blood Telomere Length Changes after Ritonavir-boosted Darunavir Combined with Raltegravir or Tenofovir-Emtricitabine in Antiretroviral-Naive Adults Infected with HIV-1. (Pubmed Central) - Sep 18, 2019 Difference in mean telomere length change between groups (tenofovir disoproxil fumarate/emtricitabine minus raltegravir) from baseline to week 96 adjusted by baseline telomere length was 0.031 (p=0.009). This difference was not significantly confounded by age, gender, known duration of HIV infection, CD4 (baseline/nadir), CD8 cells, CD4/CD8 ratio, HIV viral load (baseline/week96), tobacco and alcohol consumption, statins or hepatitis C. antiretroviral naïve HIV infected adults receiving ritonavir-boosted darunavir and tenofovir disoproxil fumarate/emtricitabine had a significant higher gain in blood telomere length than those receiving ritonavir-boosted darunavir and raltegravir suggesting a better initial recovery from HIV associated immunosenescence.
- |||||||||| Prezista (darunavir) / J&J, bictegravir (GS-9883) / Gilead, Tivicay (dolutegravir) / GSK, ViiV Healthcare
Review, Journal: Simplifying ARV Therapy in the Setting of Resistance. (Pubmed Central) - Sep 9, 2019 Currently, three- and two-drug ARV regimens may be considered in this population with most studies evaluating the use of DTG and bictegravir without baseline INSTI RAMs. Future studies should include heavily treatment-experienced patients with a variety of baseline RAMs and a larger sample size.
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Preclinical, Journal: Human intestinal fluid factors affecting intestinal drug permeation in vitro. (Pubmed Central) - Aug 30, 2019 Under those conditions, FFA and MAG no longer reduced permeation, while bile salts and phospholipids still did. This may indicate that lipidic structures can provide depot release in the case of a dynamic equilibrium between free and entrapped drug.
- |||||||||| Trial completion date, Trial primary completion date: RESIST-2: 2nd-line ART for HIV-2 Infection (clinicaltrials.gov) - Aug 19, 2019
P=N/A, N=150, Recruiting, However, due to the small number of events in the ART-N population differential risk cannot be excluded and monitoring HbA1c remains prudent. Trial completion date: Jul 2021 --> Jul 2022 | Trial primary completion date: Jan 2021 --> Jan 2022
- |||||||||| Symtuza (darunavir/cobicistat/emtricitabine/tenofovir alafenamide) / J&J, Gilead, Prezista (darunavir) / J&J
Clinical, Journal: Symtuza (DRV/c/FTC/TAF) in the management of treatment-naive HIV-patients. (Pubmed Central) - Aug 1, 2019 It therefore represents a very good regimen for naive patients, in particular those at risk of poor adherence, and those with low potential risk for drug-drug interactions. Supplement information: This article is part of a supplement entitled "Co-formulated cobicistat-boosted darunavir, emtricitabine, and tenofovir alafenamide for the treatment of HIV infection", which is sponsored by Janssen.
- |||||||||| Prezista (darunavir) / J&J, Vemlidy (tenofovir alafenamide) / Gilead
Journal: Development of darunavir over the entire spectrum of HIV infection. (Pubmed Central) - Aug 1, 2019 Its limited impact on selected mutations in the protease by other inhibitors and its high barrier against resistance have resulted in its widespread commercial use being associated with a steady decrease in the mutations circulating in the protease having an impact on its activity. Supplement information: This article is part of a supplement entitled "Co-formulated cobicistat-boosted darunavir, emtricitabine, and tenofovir alafenamide for the treatment of HIV infection", which is sponsored by Janssen.
- |||||||||| Symtuza (darunavir/cobicistat/emtricitabine/tenofovir alafenamide) / J&J, Gilead, Prezista (darunavir) / J&J, Vemlidy (tenofovir alafenamide) / Gilead
Clinical, Journal: Symtuza in clinical practice. (Pubmed Central) - Aug 1, 2019 The drug is especially useful in patients with suspected poor adherence, those requiring rapid treatment initiation because of late presentation or opportunistic infection, patients with limitations for other alternatives, and those with a history of previous failure or resistance to other classes of drugs. Supplement information: This article is part of a supplement entitled "Co-formulated cobicistat-boosted darunavir, emtricitabine, and tenofovir alafenamide for the treatment of HIV infection", which is sponsored by Janssen.
- |||||||||| Prezista (darunavir) / J&J, Reyataz (atazanavir sulfate) / BMS
Journal: Contemporary protease inhibitors and cardiovascular risk. (Pubmed Central) - Jul 19, 2019 Evidence linking protease inhibitors to CVD is based on observational studies only, whereas plausible biological explanations are well established and derived from randomized trials and controlled experiments. Given the possible association with clinical disease, a conservative approach to apply the data in daily practise is proposed which is focused on individualization of care based on underlying risk of CVD.
- |||||||||| Prezista (darunavir) / J&J, Truvada (emtricitabine/tenofovir disoproxil fumarate) / Gilead, Reyataz (atazanavir sulfate) / BMS
Clinical, Journal: Inflammatory effects of atazanavir/ritonavir versus darunavir/ritonavir in treatment naïve, HIV-1-infected patients. (Pubmed Central) - Jun 15, 2019 Our analysis provides further data examining the association between the modulation of vascular inflammatory and of activation markers with specific protease inhibitors-based treatments over one year of exposure to these drugs. The data show little evidence for an association, supporting the notion that antiretroviral regimens has generally poor efficiency in downregulating these soluble markers.
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Journal: An NMR strategy to detect conformational differences in a protein complexed with highly analogous inhibitors in solution. (Pubmed Central) - Jun 9, 2019 ...Using HIV-1 protease (PR), we previously evaluated amide chemical shift differences, ΔCSPs, of PR bound to darunavir (DRV) compared to PR bound to several DRV analogue inhibitors, to investigate subtle but significant long-distance conformation changes caused by the inhibitor's chemical moiety variation [Khan, S. N., Persons, J. D. Paulsen, J. L., Guerrero, M., Schiffer, C. A., Kurt-Yilmaz, N., and Ishima, R., Biochemistry, (2018), 57, 1652-1662]...We also verified the PR amide-water NOEs using 2D water-NOE/ROE experiments. Differences in water-amide proton NOE peaks, possibly due to amide-protein hydrogen bonds, were observed between subunit A and subunit B, and between the DRV-bound form and an analogous inhibitor-bound form, which may contribute to remote conformational changes.
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Clinical, Journal: Risk factors contributing to a low darunavir plasma concentration. (Pubmed Central) - Jun 5, 2019 The variables best predicting a darunavir concentration besides food intake included age together with estimated glomerular filtration rate (Hosmer and Lemeshow Test p=0.945, Nagelkerke R Square 0.284). Systematic evaluation of TDM results may help to identify patients at risk for low drug exposure.
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