A contemporary look at COVID-19 medications: available and potentially effective drugs.
CONCLUSIONS: We are expecting to have more cases in the coming weeks/months. Therefore, further research is needed to characterize the disease behavior, to find the absolute drug, and to refine the treatment. PMID: 32965013 [PubMed - as supplied by publisher] (Source: European Review for Medical and Pharmacological Sciences)
Source: European Review for Medical and Pharmacological Sciences - September 24, 2020 Category: Drugs & Pharmacology Tags: Eur Rev Med Pharmacol Sci Source Type: research

Molecules, Vol. 25, Pages 4075: Preparation and Characterization of Two Immunogens and Production of Polyclonal Antibody with High Affinity and Specificity for Darunavir
In this study, two new and different immunogens were prepared and characterized. These immunogens were the DRV conjugates with keyhole limpet hemocyanin (KLH) protein. The first immunogen (DRV-KLH) was prepared by zero-length direct linking of DRV via its aromatic amino group with the tyrosine amino acid residues of KLH by diazotization/coupling reaction. The second immunogen (G-DRV-KLH) was prepared by conjugation of the N-glutaryl derivative of DRV (G-DRV) with KLH. The 5-carbon atoms-spacing G-DRV hapten was synthesized by reaction of DRV via its aromatic amino group with glutaric anhydride. The reaction was monitored b...
Source: Molecules - September 7, 2020 Category: Chemistry Authors: Ibrahim A. Darwish Abdulrahman A. Almehizia Awwad A. Radwan Rashed N. Herqash Tags: Article Source Type: research

Drug repurposing approach to fight COVID-19.
Abstract Currently, there are no treatment options available for the deadly contagious disease, coronavirus disease 2019 (COVID-19). Drug repurposing is a process of identifying new uses for approved or investigational drugs and it is considered as a very effective strategy for drug discovery as it involves less time and cost to find a therapeutic agent in comparison to the de novo drug discovery process. The present review will focus on the repurposing efficacy of the currently used drugs against COVID-19 and their mechanisms of action, pharmacokinetics, dosing, safety, and their future perspective. Relevant arti...
Source: Pharmacological Reports - September 5, 2020 Category: Drugs & Pharmacology Authors: Singh TU, Parida S, Lingaraju MC, Kesavan M, Kumar D, Singh RK Tags: Pharmacol Rep Source Type: research

Analysis of type I IFN response and T cell activation in severe COVID-19/HIV-1 coinfection: A case report
Rationale: Complex immune dysregulation in interferon (IFN) and T cell response has been observed in human immunodeficiency virus (HIV-1)-infected patients as well as in coronavirus disease-2019 (COVID-19) patients. However, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)/HIV-1 coinfection has been described in only few cases worldwide and no data are available on immunological outcomes in HIV-1-patients infected with SARS-CoV-2. Hence, this study aims to compare type I IFN response and T cell activation levels between a SARS-CoV-2/HIV-1-coinfected female patient and age-matched HIV-1-positive or uninfected ...
Source: Medicine - September 4, 2020 Category: Internal Medicine Tags: Research Article: Clinical Case Report Source Type: research

Use of Darunavir-Cobicistat as a Treatment Option for Critically Ill Patients with SARS-CoV-2 Infection.
In conclusion, darunavir-cobicistat therapy was found to be associated with a significant survival benefit in critically ill patients with SARS-CoV-2 infection. PMID: 32882767 [PubMed - in process] (Source: Yonsei Medical Journal)
Source: Yonsei Medical Journal - September 1, 2020 Category: Universities & Medical Training Authors: Kim EJ, Choi SH, Park JS, Kwon YS, Lee J, Kim Y, Lee SY, Choi EY Tags: Yonsei Med J Source Type: research

Optimization of the synthetic parameters of lipid polymer hybrid nanoparticles dual loaded with darunavir and ritonavir for the treatment of HIV
Publication date: 15 October 2020Source: International Journal of Pharmaceutics, Volume 588Author(s): Heba Elkateb, Lee M. Tatham, Helen Cauldbeck, Edyta Niezabitowska, Andrew Owen, Steve Rannard, Tom McDonald (Source: International Journal of Pharmaceutics)
Source: International Journal of Pharmaceutics - August 30, 2020 Category: Drugs & Pharmacology Source Type: research

Comparative Population Pharmacokinetics of Darunavir in SARS-CoV-2 Patients vs. HIV Patients: The Role of Interleukin-6
AbstractBackgroundDarunavir is an anti-HIV protease inhibitor repurposed for SARS-CoV-2 treatment.ObjectiveThe aim of this study was to assess the population pharmacokinetics of darunavir in SARS-CoV-2 patients compared with HIV patients.MethodsTwo separate models were created by means of a nonlinear mixed-effect approach. The influence of clinical covariates on each basic model was tested and the association of significant covariates with darunavir parameters was assessed at multivariate regression and classification and regression tree (CART) analyses. Monte Carlo simulation assessed the influence of covariates on the da...
Source: Clinical Pharmacokinetics - August 27, 2020 Category: Drugs & Pharmacology Source Type: research

First case of Dolutegravir and Darunavir/r multi drug-resistant HIV-1 in Cameroon following exposure to Raltegravir: lessons and implications in the era of transition to Dolutegravir-based regimens
ConclusionsAs African countries transition to dolutegravir-based regimens, prior raltegravir-exposure may prompt selection (and potential transmission) of dolutegravir-resistance, supporting case surveillance. (Source: Antimicrobial Resistance and Infection Control)
Source: Antimicrobial Resistance and Infection Control - August 26, 2020 Category: Infectious Diseases Source Type: research

Morning vs. evening administration of antiviral therapy in COVID-19 patients. A preliminary retrospective study in Ferrara, Italy.
Authors: De Giorgi A, Fabbian F, Di Simone E, Greco S, De Giorgio R, Zuliani G, Passaro A, Caselli E, Manfredini R, OUTCOME-INTMED-COV19 Study Collaborators Abstract OBJECTIVE: At the end of 2019, the Novel Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), spread rapidly from China to the whole world. Circadian rhythms can play crucial role in the complex interplay between viruses and organisms, and temporized schedules (chronotherapy) have been positively tested in several medical diseases. We aimed to compare the possible effects of a morning vs. evening antiviral administration in COVID patients. ...
Source: European Review for Medical and Pharmacological Sciences - August 14, 2020 Category: Drugs & Pharmacology Tags: Eur Rev Med Pharmacol Sci Source Type: research

Pharmacokinetic Enhancement of HIV Antiretroviral Therapy During Pregnancy.
The objectives of this article are to review pharmacokinetic enhancement of ARVs with ritonavir and cobicistat during pregnancy and postpartum, describe clinical implications, and provide recommendations for future research. PMID: 32798276 [PubMed - as supplied by publisher] (Source: The Journal of Clinical Pharmacology)
Source: The Journal of Clinical Pharmacology - August 14, 2020 Category: Drugs & Pharmacology Authors: Salama E, Eke AC, Best BM, Mirochnick M, Momper JD Tags: J Clin Pharmacol Source Type: research

Molecular Docking and Virtual Screening based prediction of drugs for COVID-19.
CONCLUSION: Protease inhibitors approved for treatment of other viral diseases have the potential to be repurposed for treatment of COVID-19. PMID: 32798373 [PubMed - as supplied by publisher] (Source: Combinatorial Chemistry and High Throughput Screening)
Source: Combinatorial Chemistry and High Throughput Screening - August 14, 2020 Category: Chemistry Authors: Talluri S Tags: Comb Chem High Throughput Screen Source Type: research

Anti-Inflammatory Properties of Drugs Used to Control COVID-19 and their Effects on the Renin-Angiotensin System and Angiotensin-Converting Enzyme-2.
Authors: Gilzad-Kohan H, Jamali F Abstract COVID-19 infection is associated with systemic inflammation, and sometimes hyperinflammatory responses with cytokine storm. This plays a major role in COVID-19 severity and poor disease prognosis, even death. Higher levels of inflammatory hallmarks including C-reactive protein, ferritin, D-dimers, and cytokines such as interleukin (IL) -6, IL-10 and tumor necrosis factor- α (TNF-α) have been reported. Many anti-viral drugs have been tried, but none were proven fully effective. Supportive care and management of the complications that are caused mainly by inflamm...
Source: Journal of Pharmacy and Pharmaceutical Sciences - August 1, 2020 Category: Drugs & Pharmacology Tags: J Pharm Pharm Sci Source Type: research

Real-World Experience with Dolutegravir-Based Two-Drug Regimens.
Conclusions: Prior to commercial availability of the single-tablet 2DRs, DTG 2DR components were primarily used in treatment-experienced patients for treatment simplification and avoidance of long-term toxicities. Many of these patients achieved and maintained virologic suppression, with low discontinuation rates. PMID: 32724674 [PubMed] (Source: AIDS Research and Treatment)
Source: AIDS Research and Treatment - July 31, 2020 Category: Infectious Diseases Tags: AIDS Res Treat Source Type: research

“String of Pearls” Sign revealing Linear IgA bullous disease
A 21-year-old HIV-positive male on antiretroviral treatment with daily darunavir/cobicistat and emtricitabine/tenofovir presented with a 2-week history of pruritic skin lesions on both shoulders and the face. The patient denied any other symptoms. Antiretroviral treatment had not been recently changed, his viral load was undetectable and there was no other relevant medical history. On physical examination, he was in good general health and vital signs were within normal limits. He had scant erythematous macules on both shoulders and three clear grouped vesicles on the right forehead. (Source: The American Journal of Medicine)
Source: The American Journal of Medicine - July 28, 2020 Category: General Medicine Authors: Paula D íaz-Morales, Mercè Grau-Pérez, Mª Pilar De-la-Rosa-Del-Rey, Miguel-Ángel Cárdenes-Santana Tags: Clinical Communication to the Editor Source Type: research

‘String of Pearls’ Sign Revealing Linear IgA Bullous Disease
A 21-year-old HIV (Human Immunodeficiency Virus)-positive male on antiretroviral treatment with daily darunavir-cobicistat and emtricitabine-tenofovir presented with a 2-week history of pruritic skin lesions on both shoulders and the face. The patient denied any other symptoms. Antiretroviral treatment had not been recently changed, his viral load was undetectable, and there was no other relevant medical history. On physical examination, he was in good general health and vital signs were within normal limits. (Source: The American Journal of Medicine)
Source: The American Journal of Medicine - July 28, 2020 Category: General Medicine Authors: Paula D íaz-Morales, Mercè Grau-Pérez, Mª Pilar De-La-Rosa-Del-Rey, Miguel-Ángel Cárdenes-Santana Tags: Clinical Communication to the Editor Source Type: research

Exploration of Reduced Doses and Short-Cycle Therapy for Darunavir/Cobicistat in Patients with HIV Using Population Pharmacokinetic Modeling and Simulations
ConclusionsThese results add to the growing body of evidence that darunavir-based therapy could be simplified to reduce costs and toxicity, as well as to improve patient compliance. However, the heterogeneity in pharmacokinetic response should be considered when assessing whether individual patients could benefit from a particular regimen, for instance through the use of population pharmacokinetic models.Clinical Trial RegistrationClinicalTrials.gov identifier: NCT03101644, date of registration: 5 April, 2017. (Source: Clinical Pharmacokinetics)
Source: Clinical Pharmacokinetics - July 22, 2020 Category: Drugs & Pharmacology Source Type: research

Effectiveness of the combination elvitegravir/cobicistat/tenofovir/emtricitabine (EVG/COB/TFV/FTC) plus darunavir among treatment-experienced patients in clinical practice: a multicentre cohort study
The aim of this study was to investigate the effectiveness and tolerability of the combination elvitegravir/cobicistat/tenofovir/emtricitabine plus darunavir (EVG/COB/TFV/FTC  + DRV) in treatment-experienced pa... (Source: AIDS Research and Therapy)
Source: AIDS Research and Therapy - July 20, 2020 Category: Infectious Diseases Authors: In és Suárez-García, Cristina Moreno, Marta Ruiz-Algueró, María Jesús Pérez-Elías, Marta Navarro, Marcos Díez Martínez, Pompeyo Viciana, Laura Pérez-Martínez, Miguel Górgolas, Concha Amador, Miguel Alberto de Zárraga and Inma Jarrín Tags: Research Source Type: research

Effectiveness of the combination elvitegravir/cobicistat/tenofovir/emtricitabine (EVG/COB/TFV/FTC) plus darunavir among treatment-experienced patients in clinical practice: a multicentre cohort study.
arrín I, Cohort of the Spanish HIV/AIDS Research Network (CoRIS) Abstract BACKGROUND: The aim of this study was to investigate the effectiveness and tolerability of the combination elvitegravir/cobicistat/tenofovir/emtricitabine plus darunavir (EVG/COB/TFV/FTC + DRV) in treatment-experienced patients from the cohort of the Spanish HIV/AIDS Research Network (CoRIS). METHODS: Treatment-experienced patients starting treatment with EVG/COB/TFV/FTC + DRV during the years 2014-2018 and with more than 24 weeks of follow-up were included. TFV could be administered either as ten...
Source: AIDS Research and Therapy - July 20, 2020 Category: Infectious Diseases Authors: Suárez-García I, Moreno C, Ruiz-Algueró M, Pérez-Elías MJ, Navarro M, Díez Martínez M, Viciana P, Pérez-Martínez L, Górgolas M, Amador C, de Zárraga MA, Jarrín I, Cohort of the Spanish HIV/AIDS Research Network (CoRIS) Tags: AIDS Res Ther Source Type: research

Effects on QT interval of hydroxychloroquine associated with ritonavir/darunavir or azithromycin in patients with SARS-CoV-2 infection
ConclusionHydroxychloroquine with both ritonavir/darunavir or azithromycin therapy significantly increased the QTc-interval at 7  days. The risk of developing malignant arrhythmias remained relatively low when these drugs were administered for a limited period of time. (Source: Heart and Vessels)
Source: Heart and Vessels - July 16, 2020 Category: Cardiology Source Type: research

Covid-19: A systemic disease treated with a wide-ranging approach: A case report.
Authors: Massabeti R, Cipriani MS, Valenti I Abstract At the end of December 2019, the Health Commission of the city of Wuhan, China, alerted the World Health Organization (WHO) to a pneumonia cluster in the city. The cause was identified as being a new virus, later named SARS-CoV-2. We can distinguish three clinical phases of the disease with a distinct pathogenesis, manifestations and prognosis. Here, we describe the case of a 45-year-old male, successfully treated for Coronavirus disease (COVID-19). The patient was feeling sick in early April 2020; he had a fever and pharyngodynia. When he came to our COVID hosp...
Source: Journal of Population Therapeutics and Clinical Pharmacology - July 12, 2020 Category: Drugs & Pharmacology Tags: J Popul Ther Clin Pharmacol Source Type: research

Application of Physiologically ‐based Pharmacokinetic Modeling to Predict Gastric pH‐dependent Drug‐drug Interactions for Weak Base Drugs
AbstractWeak base drugs (WBDs) are susceptible to drug ‐drug interactions (DDIs) when co‐administered with gastric acid reducing agents (ARAs). We developed PBPK models to evaluate the potential of such pH‐dependent DDIs for 4 WBDs, i.e., tapentadol, darunavir, erlotinib, and saxagliptin. The PBPK models of these drugs were first optimized using P K data following oral administration without ARAs, which were then verified with data from additional PK studies in the presence and absence of food. The models were subsequently utilized to predict the extent of DDIs with ARA co‐administration. Sensitivity analysis was c...
Source: CPT: Pharmacometrics and Systems Pharmacology - July 7, 2020 Category: Drugs & Pharmacology Authors: Zhongqi Dong, Jia Li, Fang Wu, Ping Zhao, Sue ‐Chih Lee, Lillian Zhang, Paul Seo, Lei Zhang Tags: ARTICLE Source Type: research

Molecules, Vol. 25, Pages 2944: Data and Text Mining Help Identify Key Proteins Involved in the Molecular Mechanisms Shared by SARS-CoV-2 and HIV-1
Poroikov Viruses can be spread from one person to another; therefore, they may cause disorders in many people, sometimes leading to epidemics and even pandemics. New, previously unstudied viruses and some specific mutant or recombinant variants of known viruses constantly appear. An example is a variant of coronaviruses (CoV) causing severe acute respiratory syndrome (SARS), named SARS-CoV-2. Some antiviral drugs, such as remdesivir as well as antiretroviral drugs including darunavir, lopinavir, and ritonavir are suggested to be effective in treating disorders caused by SARS-CoV-2. There are data on the utilization of ...
Source: Molecules - June 26, 2020 Category: Chemistry Authors: Tarasova Ivanov Filimonov Poroikov Tags: Communication Source Type: research

Effectiveness of Switching to Darunavir/Cobicistat in Virologically Suppressed HIV-Positive Patients Receiving Ritonavir-Boosted Protease Inhibitor–Based Regimen: The “STORE” Study
This study investigates the effectiveness and tolerability of switching to a darunavir/cobicistat (DRV/c)-based antiretroviral regimen from a ritonavir-boosted protease inhibitor (PI/r)-based regimen in virologically suppressed HIV-positive patients. DRV trough values were also investigated. Setting: Prospective, multicenter, single-country, noninterventional cohort study. Methods: This study included patients on a PI/r-based ART for at least 12 months having plasma HIV-1 RNA (Source: JAIDS Journal of Acquired Immune Deficiency Syndromes)
Source: JAIDS Journal of Acquired Immune Deficiency Syndromes - June 16, 2020 Category: Infectious Diseases Tags: Clinical Science Source Type: research

Two treatment strategies for management of Neurosymptomatic cerebrospinal fluid HIV escape in Pune, India
Symptomatic cerebrospinal fluid (CSF) viral escape (sCVE) is reported in people with HIV, who are on ritonavir-boosted protease inhibitor (PI/r) containing antiretroviral therapy (ART). Management of sCVE includes performing genotypic HIV-1 resistance testing (GRT) on CSF and plasma HIV and changing ART accordingly. Neither GRT nor newer drugs (Dolutegravir and Darunavir/ritonavir) are routinely available in India. As a result, management of sCVE includes 2 modalities: a) ART intensification by adding drugs that reach therapeutic concentrations in CSF, like Zidovudine, to existing ART or b) Changing to a regimen containing...
Source: Medicine - June 12, 2020 Category: Internal Medicine Tags: Research Article: Observational Study Source Type: research

Correction to: Patient-Reported Outcomes in an Observational Cohort of HIV-1-Infected Adults on Darunavir/Cobicistat-Based Regimens: Beyond Viral Suppression
In the original version of this article, in Fig.  2b the formatting on the x-axis of the graph has been published incorrectly. (Source: The Patient - Patient-Centered Outcomes Research)
Source: The Patient - Patient-Centered Outcomes Research - May 29, 2020 Category: International Medicine & Public Health Source Type: research

Lack of Antiviral Activity of Darunavir against SARS-CoV-2
(Source: International Journal of Infectious Diseases)
Source: International Journal of Infectious Diseases - May 29, 2020 Category: Infectious Diseases Authors: Sandra De Meyer, Denisa Bojkova, Jindrich Cinatl, Ellen Van Damme, Christophe Buyck Meng, Marnix Van Loock, Brian Woodfall, Sandra Ciesek Source Type: research

Darunavir inhibits Cryptococcus neoformans/Cryptococcus gattii species complex growth and increases the susceptibility of biofilms to antifungal drugs.
a MFG Abstract Introduction. Cryptococcus species are pathogens commonly associated with cases of meningoencephalitis in individuals who are immunosuppressed due to AIDS.Aim. The aim was to evaluate the effects of the antiretroviral darunavir alone or associated with fluconazole, 5-flucytosine and amphotericin B against planktonic cells and biofilms of Cryptococcus species.Methodology. Susceptibility testing of darunavir and the common antifungals against 12 members of the Cryptococcus neoformans/Cryptococcus gattii species complex was evaluated by broth microdilution. The interaction between darunavir and antifun...
Source: Journal of Medical Microbiology - May 27, 2020 Category: Microbiology Authors: Brilhante RSN, Silva JAT, Araújo GDS, Pereira VS, Gotay WJP, Oliveira JS, Guedes GMM, Pereira-Neto WA, Castelo-Branco DSCM, Cordeiro RA, Sidrim JJC, Rocha MFG Tags: J Med Microbiol Source Type: research

COVID-19 in people living with human immunodeficiency virus: a case series of 33 patients
ConclusionsThis preliminary case series does not support excess morbidity and mortality among symptomatic COVID-19 PLWH and with viral suppression on ART. SARS-CoV-2 infections may occur during boosted darunavir-based and/or on tenofovir-containing ART. (Source: Infection)
Source: Infection - May 11, 2020 Category: Infectious Diseases Source Type: research

Direct oral anticoagulant plasma levels striking increase in severe COVID-19 respiratory syndrome patients treated with antiviral agents. The Cremona experience.
CONCLUSION: DOAC patients treated with antiviral drugs show an alarming increase in DOAC plasma levels. In order to prevent bleeding complications, we believe that physicians should consider withholding DOACs from patients with SARS-CoV-2 and replacing them with alternative parenteral antithrombotic strategies for as long as antiviral agents are deemed necessary and until discharge. PMID: 32329231 [PubMed - as supplied by publisher] (Source: Thrombosis and Haemostasis)
Source: Thrombosis and Haemostasis - April 23, 2020 Category: Hematology Authors: Testa S, Prandoni P, Paoletti O, Morandini R, Tala M, Dellanoce C, Giorgi-Pierfranceschi M, Betti M, Danzi GB, Pan A, Palareti G Tags: J Thromb Haemost Source Type: research

Darunavir does not prevent SARS-CoV-2 infection in HIV patients
Publication date: Available online 20 April 2020Source: Pharmacological ResearchAuthor(s): Agostino Riva, Federico Conti, Dario Bernacchia, Laura Pezzati, Salvatore Sollima, Stefania Merli, Matteo Siano, Angelica Lupo, Stefano Rusconi, Dario Cattaneo, Cristina Gervasoni (Source: Pharmacological Research)
Source: Pharmacological Research - April 21, 2020 Category: Drugs & Pharmacology Source Type: research

Development of darunavir proliposome powder for oral delivery by using box-bhenken design.
Authors: Bhusari S, Ansari I, Chaudhary A Abstract The aim of present study is to develop Darunavir pro-liposome powder for oral delivery. Darunavir-loaded oral pro-liposome powder (OPP) was prepared by a solvent evaporation technique with varying independent variables at three different levels. Based on different levels pro-liposome powder formulation was optimized by using Box-Behnken design. The formulations were analyzed for its size distribution, entrapment efficiency and surface morphology. Optimized pro-liposome batch A was evaluated for physical parameter, morphological parameters, entrapment efficiency, fo...
Source: Drug Development and Industrial Pharmacy - April 16, 2020 Category: Drugs & Pharmacology Tags: Drug Dev Ind Pharm Source Type: research

SARS CoV-2: Recent Reports on Antiviral Therapies Based on Lopinavir/Ritonavir, Darunavir/Umifenovir, Hydroxychloroquine, Remdesivir, Favipiravir and Other Drugs for the Treatment of the New Coronavirus.
Abstract Here we report on the most recent updates on experimental drugs successfully employed in the treatment of the disease caused by SARS CoV-2 coronavirus, also referred to as COVID-19 (COronaVIrus Disease 19). In particular, several cases of recovered patients have been reported after being treated with lopinavir/ritonavir (which is widely used to treat human immunodeficiency virus (HIV) infection) in combination with the anti-flu drug oseltamivir. In addition, remdesivir, which has been previously administered to Ebola virus patients, has also proven effective in the U.S. against coronavirus, while antimala...
Source: Current Medicinal Chemistry - April 16, 2020 Category: Chemistry Authors: Costanzo M, De Giglio MAR, Roviello GN Tags: Curr Med Chem Source Type: research

Aging does not impact drug--drug interaction magnitudes with antiretrovirals
The risk of drug–drug interactions (DDIs) is elevated in aging people living with HIV (PLWH) because of highly prevalent age-related comorbidities leading to more comedications. To investigate the impact of aging on DDI magnitudes between comedications (amlodipine, atorvastatin, rosuvastatin) and boosted darunavir, we conducted a clinical trial in aging PLWH aged at least 55 years. DDI magnitudes were comparable with those reported in young individuals supporting that the clinical management of DDIs in aging PLWH can be similar. (Source: AIDS)
Source: AIDS - April 9, 2020 Category: Infectious Diseases Tags: Research Letters Source Type: research

Patient-Reported Outcomes in an Observational Cohort of HIV-1-Infected Adults on Darunavir/Cobicistat-Based Regimens: Beyond Viral Suppression
AbstractObjectiveThis prospective, multicenter, non-interventional cohort study enrolling human immunodeficiency virus (HIV)-1-infected, virally suppressed adult outpatients in Italy aimed to describe results obtained from patient-reported outcome questionnaires regarding treatment satisfaction and symptom perceptions in HIV-1-positive patients who switched to cobicistat-boosted darunavir antiretroviral regimens, coming from ritonavir-boosted protease inhibitors.MethodsPatients entered this study between June 2016 and February 2017, once their treating physician had considered them eligible for cobicistat-boosted darunavir...
Source: The Patient - Patient-Centered Outcomes Research - April 8, 2020 Category: International Medicine & Public Health Source Type: research

Benign COVID-19 in an immunocompromised cancer patient -   the case of a married couple.
Benign COVID-19 in an immunocompromised cancer patient -  the case of a married couple. Swiss Med Wkly. 2020 Apr 06;150:w20246 Authors: Spezzani V, Piunno A, Iselin HU Abstract Respiratory failure in COVID-19 is a common feature in fatal cases and has been considered as a failure of the immune system to control the virus. Here we report the case of COVID-19 affecting an immunocompromised women and her presumably immunocompetent spouse. A married couple (age 60 years) was simultaneously admitted to the emergency department on 10 March 2020 because of dyspnoea and fever, consistent with COVID-19. T...
Source: Swiss Medical Weekly - April 6, 2020 Category: General Medicine Authors: Spezzani V, Piunno A, Iselin HU Tags: Swiss Med Wkly Source Type: research

Drug-Drug Interactions Between Antiretrovirals and Carbamazepine/Oxcarbazepine: A Real-Life Investigation
Background: Carbamazepine and oxcarbazepine are potent modulators of metabolic enzymes. Hence, potential drug-drug interactions (DDIs) may occur between these 2 drugs and antiretrovirals. Here, we aimed to assess the relevance of these drug-drug interactions in real-life clinical settings. Methods: Patients treated concomitantly with carbamazepine or oxcarbazepine and antiretrovirals for at least 3 months were considered. Data on therapeutic drug monitoring (TDM) of both antiepileptic and antiretrovirals as trough concentrations were collected. HIV-infected patients not concomitantly treated with antiepileptic drugs a...
Source: Therapeutic Drug Monitoring - March 20, 2020 Category: Drugs & Pharmacology Tags: Short Communication Source Type: research

Doravirine: a new non-nucleoside reverse transcriptase inhibitor for the treatment of HIV infection.
Authors: Talwani R, Temesgen Z Abstract Doravirine is a new non-nucleoside reverse transcriptase inhibitor (NNRTI) that was approved by the United States Food and Drug Administration (FDA) on August 30, 2018, for the treatment of HIV infection in adult patients. The product was also approved in the E.U. and Japan in November 2018 and January 2020, respectively. It is currently available as a single stand-alone tablet as well as part of a single-tablet regimen in a fixed-dose combination with tenofovir disoproxil and lamivudine. Similarly to other NNRTIs, doravirine exerts its antiviral effect through a noncompetiti...
Source: Drugs of Today - March 14, 2020 Category: Drugs & Pharmacology Tags: Drugs Today (Barc) Source Type: research

Week 96 results of a phase 3 trial of darunavir/cobicistat/emtricitabine/tenofovir alafenamide in treatment-naive HIV-1 patients
Background: Darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) 800/150/200/10 mg was investigated through 96 weeks in AMBER (NCT02431247). Methods: Treatment-naive, HIV-1-positive adults [screening plasma viral load ≥1000 copies/ml; CD4+ cell count>50 cells/μl) were randomized (1 : 1) to D/C/F/TAF (N = 362) or D/C plus emtricitabine/tenofovir-disoproxil-fumarate (F/TDF) (N = 363) over at least 48 weeks. After week 48, patients could continue on or switch to D/C/F/TAF in an open-label extension phase until week 96. Results: At week 96, D/C/F/TAF exposure was 626 patient-y...
Source: AIDS - March 14, 2020 Category: Infectious Diseases Tags: CLINICAL SCIENCE Source Type: research

Antiretroviral Therapy Concentrations Differ in Gut vs. Lymph Node Tissues and Are Associated With HIV Viral Transcription by a Novel RT-ddPCR Assay
Background: Most HIV-infected cells during antiretroviral therapy (ART) persist in lymphoid tissues. Studies disagree on whether suboptimal tissue ART concentrations contribute to ongoing HIV replication during viral suppression. Methods: We performed a cross-sectional study in virally-suppressed HIV+ participants measuring lymphoid tissue ART [darunavir (DRV), atazanavir (ATV), and raltegravir (RAL)] concentrations by LC-MS/MS assay. Tissue and plasma ART concentrations were used to estimate TPRs and drug-specific tissue:inhibitory concentration ratios (TICs). HIV DNA and sequentially produced HIV RNA transcripts wer...
Source: JAIDS Journal of Acquired Immune Deficiency Syndromes - March 12, 2020 Category: Infectious Diseases Tags: Translational Research Source Type: research

Darunavir Pharmacokinetics With an Increased Dose During Pregnancy
This study aims to evaluate the pharmacokinetics of an increased dose of darunavir (800 mg twice daily) with 100 mg ritonavir during pregnancy and postpartum. Methods: Darunavir (DRV) and ritonavir (RTV; r) intensive pharmacokinetic evaluations were performed at steady state during the second and third trimesters of pregnancy (DRV/r 800/100 mg bid) and 2–3 weeks postpartum (DRV/r 600/100 mg twice daily). Plasma concentrations of darunavir and ritonavir were measured using high-performance liquid chromatography. Target darunavir area under the concentration time curve (AUC) was>70% (43.6 μg × h/mL) of m...
Source: JAIDS Journal of Acquired Immune Deficiency Syndromes - February 27, 2020 Category: Infectious Diseases Tags: Clinical Science Source Type: research

[ASAP] < italic toggle="yes" > In Vivo < /italic > Modulation of Cervicovaginal Drug Transporters and Tissue Distribution by Film-Released Tenofovir and Darunavir for Topical Prevention of HIV-1
Molecular PharmaceuticsDOI: 10.1021/acs.molpharmaceut.9b01121 (Source: Molecular Pharmaceutics)
Source: Molecular Pharmaceutics - February 20, 2020 Category: Drugs & Pharmacology Authors: Karolin Hijazi* †, Francesco Iannelli‡, Anna Maria Cuppone‡, Delphine Desjardins§, Anna Caldwell?, Nathalie Dereuddre-Bosquet§, Carlo Scala?, Kieron A. Smith†, Indrani Mukhopadya†, Bruce Frank#, Garry Gwozdz#, Francesco Santoro‡, Roger Le Gr Source Type: research

The Molecular Docking, Synthesis and anti-HIV-1 protease Activity of Novel Chalcones.
CONCLUSION: It is difficult to provide general principles of inhibitor design. Structural properties of the compounds are not the only consideration; ease of chemical synthesis, low molecular weight, bioavailability, and stability are also of crucial importance. Compared to commercial products the main advantage of compound C1 is ease of chemical synthesis and low molecular weight. Furthermore, compound C1 has a structure that is different to peptidomimetics, which could contribute to its stability and bioavailability. PMID: 32013827 [PubMed - as supplied by publisher] (Source: Current Pharmaceutical Design)
Source: Current Pharmaceutical Design - February 3, 2020 Category: Drugs & Pharmacology Authors: Turkovic N, Ivkovic B, Kotur-Stevuljevic J, Tasic M, Marković B, Vujic Z Tags: Curr Pharm Des Source Type: research

HPLC-MS/MS method for the simultaneous quantification of dolutegravir, elvitegravir, rilpivirine, darunavir, ritonavir, raltegravir and raltegravir-β-D-glucuronide in human plasma
Publication date: Available online 18 January 2020Source: Journal of Pharmaceutical and Biomedical AnalysisAuthor(s): Yi Zheng, Radia Aboura, Sana Boujaafar, Gabrielle Lui, Déborah Hirt, Naïm Bouazza, Frantz Foissac, Jean-Marc Treluyer, Sihem Benaboud, Inès GanaAbstractTherapeutic drug monitoring (TDM) is essential in the optimization of antiretroviral (ARV) treatments. In this work, we describe a new method for the simultaneous quantification of six molecules: the three novel ARV agents dolutegravir (DTG), elvitegravir (ELV) and rilpivirine (RPV), the first integrase inhibitor raltegravir (RAL) and its ...
Source: Journal of Pharmaceutical and Biomedical Analysis - January 19, 2020 Category: Drugs & Pharmacology Source Type: research

Lack of impact of protease inhibitor resistance-associated mutations on the outcome of HIV-1-infected patients switching to darunavir-based dual therapy
. (Source: Infectious Diseases)
Source: Infectious Diseases - December 17, 2019 Category: Infectious Diseases Authors: Pilar Vizcarra Jos é L. Blanco Roc ío Montejano Eugenia Negredo Nuria Espinosa Jos é L. Casado Source Type: research

Pharmacokinetic profiles of boosted darunavir, dolutegravir and lamivudine in aging people living with HIV
Objectives: The pharmacokinetics of antiretroviral drugs may differ in elderly people living with HIV (PLWH) because of age-related physiological changes. We aimed to assess the pharmacokinetics of several antiretroviral drugs in aging PLWH enrolled in the Swiss HIV Cohort (SHCS). Design: Full pharmacokinetic profiling nested in a multicenter, observational, prospective cohort study. Additional collection of single point pharmacokinetic data during SHCS follow-up visits (unselected PLWH). Methods: PLWH were eligible for the full pharmacokinetics investigation if they were over the age of 55 years, on a stable boost...
Source: AIDS - December 3, 2019 Category: Infectious Diseases Tags: CONCISE COMMUNICATION Source Type: research

Weight gain in people living with HIV switched to dual therapy: changes in body fat mass
Changes in weight and body composition were assessed in long-term suppressed HIV-infected patients switching to dolutegravir/rilpivirine (n = 37), and compared with similar patients switching to darunavir/lamivudine (n = 17). At month 12, weight significantly increased with dolutegravir/rilpivirine (1.8 kg, IQR −1.2 to 4.1; 2.5%; P = 0.03). A follow-up DXA (median, 16 months) showed similar increases in trunk (7.8%), arms (5.6%), and legs (6.2%) fat mass, without changes in lean mass. Despite lower weight gain (0.70 kg, IQR −0.8 to 4.0, P = 0.28), fat mass increase was similar in the darunav...
Source: AIDS - December 3, 2019 Category: Infectious Diseases Tags: Research Letter Source Type: research

[ASAP] Synthesis and Characterization of Long-Acting Darunavir Prodrugs
Molecular PharmaceuticsDOI: 10.1021/acs.molpharmaceut.9b00871 (Source: Molecular Pharmaceutics)
Source: Molecular Pharmaceutics - December 3, 2019 Category: Drugs & Pharmacology Authors: Mary G. Banoub †, Aditya N. Bade†, Zhiyi Lin†, Denise Cobb†, Nagsen Gautam‡, Bhagya Laxmi Dyavar Shetty†, Melinda Wojtkiewicz†, Yazen Alnouti‡, JoEllyn McMillan†, Howard E. Gendelman*†, and Benson Edagwa*† Source Type: research

Protease Inhibitors, Saquinavir and Darunavir, Inhibit Oligodendrocyte Maturation: Implications for Lysosomal Stress
AbstractDespite the introduction of antiretroviral (ARV) therapy (ART), approximately 30 –50% of people living with human immunodeficiency virus-1 (HIV-1) will develop a spectrum of measurable neurocognitive dysfunction, collectively called HIV-associated neurocognitive disorder (HAND). While the clinical manifestations of HAND have changed with the advent of ART, certain pathological features have endured, including white matter alterations and dysfunction. The persistence of white matter alterations in the post-ART era suggests that ARV drugs themselves may contribute to HAND pathology. Our group has previously dem...
Source: Journal of NeuroImmune Pharmacology - November 28, 2019 Category: Drugs & Pharmacology Source Type: research

Lack of impact of protease inhibitor resistance-associated mutations on the outcome of HIV-1-infected patients switching to darunavir-based dual therapy
. (Source: Infectious Diseases)
Source: Infectious Diseases - November 25, 2019 Category: Infectious Diseases Authors: Pilar Vizcarra Jos é L. Blanco Roc ío Montejano Eugenia Negredo Nuria Espinosa Jos é L. Casado Source Type: research