Search results for "Anti-HIV Agents"

showing 10 items of 90 documents

Tenofovir-induced toxicity in renal proximal tubular epithelial cells

2017

OBJECTIVE In-vivo studies suggest that mitochondria is involved in tenofovir (TFV)-induced renal toxicity, but the underlying mechanisms are still unclear. The aim of the present study was to assess the effects of TFV and its prodrug, TFV disoproxil fumarate, on mitochondrial function and cell survival/viability in a renal proximal tubular cell line. DESIGN AND METHODS We evaluated parameters of cellular proliferation/survival (cell count, cell cycle, viability) and mitochondrial function (oxygen consumption, mitochondrial membrane potential, reactive oxygen species production) in NRK-52E cells. Intracellular TFV was measured by HPLC and expression of antioxidant genes was analysed by real-…

0301 basic medicineAnti-HIV AgentsCell Survival030106 microbiologyImmunologyCellOxidative phosphorylationMitochondrionPharmacologyCell Line03 medical and health sciencesmedicineHumansImmunology and AllergyTenofovirCell Proliferationchemistry.chemical_classificationKidneyReactive oxygen speciesCell growthEpithelial Cellsmedicine.diseaseMitochondriaMitochondrial toxicity030104 developmental biologyInfectious Diseasesmedicine.anatomical_structurechemistryIntracellularAIDS
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Abacavir induces platelet-endothelium interactions by interfering with purinergic signalling: A step from inflammation to thrombosis.

2017

The controversy connecting Abacavir (ABC) with cardiovascular disease has been fuelled by the lack of a credible mechanism of action. ABC shares structural similarities with endogenous purines, signalling molecules capable of triggering prothrombotic/proinflammatory programmes. Platelets are leading actors in the process of thrombosis. Our study addresses the effects of ABC on interactions between platelets and other vascular cells, while exploring the adhesion molecules implicated and the potential interference with the purinergic signalling pathway. The effects of ABC on platelet aggregation and platelet-endothelium interactions were evaluated, respectively, with an aggregometer and a flo…

0301 basic medicineBlood PlateletsEndotheliumPlatelet AggregationAnti-HIV AgentsInflammationPharmacologyBiologyProinflammatory cytokine03 medical and health sciences0302 clinical medicinePlatelet Adhesivenessplatelet-endothelium interactionsVirologymedicineHumansPlatelet030212 general & internal medicinePlatelet activationPharmacologyInflammationCell adhesion moleculePurinergic receptorDeoxyguanine NucleotidesThrombosisPurinergic signallingIntercellular Adhesion Molecule-1Platelet ActivationAbacavirNRTIsDideoxynucleosidesCell biologycardiovascular diseasesP-Selectin030104 developmental biologymedicine.anatomical_structureCardiovascular DiseasesPurinesEndothelium Vascularmedicine.symptomSignal TransductionAntiviral research
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Abacavir Induces Arterial Thrombosis in a Murine Model.

2018

Background The purinergic system is known to underlie prothrombotic and proinflammatory vascular programs, making the profile of experimental actions demonstrated by abacavir compatible with thrombogenesis. However, direct evidence of a prothrombotic effect by the drug has been lacking. Methods The present study appraised the effects of abacavir in a well-validated animal model of arterial thrombosis. The role of ATP-P2X7 receptors in the actions of the drug was also assessed, and the actions of recognized vascular-damaging agents and other nucleoside reverse-transcriptase inhibitors (NRTIs) were evaluated and compared to those of abacavir. Results Abacavir dose-dependently promoted thrombu…

0301 basic medicineDrugMaleAnti-HIV Agentsmedia_common.quotation_subject030204 cardiovascular system & hematologyPharmacologyProinflammatory cytokine03 medical and health sciences0302 clinical medicineimmune system diseasesAbacavirmedicineImmunology and AllergyAnimalsRofecoxibmedia_commonMice KnockoutDose-Response Relationship Drugbusiness.industryPurinergic receptorAntagonistvirus diseasesThrombosisPurinergic signallingmedicine.diseaseThrombosisDideoxynucleosidesDisease Models Animal030104 developmental biologyInfectious DiseasesReceptors Purinergic P2X7businessmedicine.drugThe Journal of infectious diseases
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Cardiovascular toxicity of abacavir: a clinical controversy in need of a pharmacological explanation.

2017

: There is a long-lasting controversy surrounding an association between abacavir (ABC) and an increased risk of cardiovascular disease in HIV-positive patients. Although differing in their specifics, a number of published cohort studies and clinical trials support such an association, usually relating it to recent exposure to the drug, independently of traditional predisposing factors. However, other clinical trials have failed to reveal such a relation and have pointed to methodological differences to explain discrepancies. Significantly, the controversy has been fueled by the lack of a credible mechanism of action to justify the putative detrimental actions of ABC. There is a myriad of c…

0301 basic medicineDrugVasculitisAnti-HIV Agentsmedia_common.quotation_subjectImmunologyHIV InfectionsDiseasePharmacologyBioinformaticsProinflammatory cytokine03 medical and health sciencesParacrine signallingchemistry.chemical_compound0302 clinical medicineAbacavirImmunology and AllergyMedicineHumans030212 general & internal medicineCyclic guanosine monophosphatemedia_commonbusiness.industryAtherosclerosis030112 virologyDideoxynucleosidesClinical trialInfectious DiseaseschemistryMechanism of actionCardiovascular Diseasesmedicine.symptombusinessmedicine.drugAIDS (London, England)
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Switching to dual/monotherapy determines an increase in CD8+ in HIV-infected individuals: An observational cohort study

2018

Background The CD4/CD8 ratio has been associated with the risk of AIDS and non-AIDS events. We describe trends in immunological parameters in people who underwent a switch to monotherapy or dual therapy, compared to a control group remaining on triple antiretroviral therapy (ART). Methods We included patients in Icona who started a three-drug combination ART regimen from an ART-naïve status and achieved a viral load ≤ 50 copies/mL; they were subsequently switched to another triple or to a mono or double regimen. Standard linear regression at fixed points in time (12-24 months after the switch) and linear mixed model analysis with random intercepts and slopes were used to compare CD4 and CD8…

0301 basic medicineMaleCD4-CD8 Ratiolcsh:MedicineHIV InfectionsCD8-Positive T-LymphocytesCD4/CD8 ratio; CD8; Chronic inflammation; Dual therapy; Monotherapy; Adult; Anti-HIV Agents; CD4-CD8 Ratio; CD8-Positive T-Lymphocytes; Cohort Studies; Emtricitabine; Female; HIV Infections; Humans; Male; Middle Aged; Reverse Transcriptase Inhibitors; Tenofovir; Medicine (all)Cohort Studies0302 clinical medicineEmtricitabineHIV Infection030212 general & internal medicineMedicine (all)General MedicineChronic inflammationCD4/CD8 ratio; CD8; Chronic inflammation; Dual therapy; Monotherapy; Medicine (all)Middle AgedSettore MED/07 - Microbiologia e Microbiologia ClinicaReverse Transcriptase InhibitorReverse Transcriptase InhibitorsFemalecd4/cd8 ratio; cd8; chronic inflammation; dual therapy; monotherapy; medicine (all)Research Articlemedicine.drugCohort studyHumanAdultmedicine.medical_specialtyDual therapyCD4/CD8 ratio; CD8; Chronic inflammation; Dual therapy; Monotherapy; Adult; Anti-HIV Agents; CD4-CD8 Ratio; CD8-Positive T-Lymphocytes; Cohort Studies; Emtricitabine; Female; HIV Infections; Humans; Male; Middle Aged; Reverse Transcriptase Inhibitors; TenofovirAnti-HIV Agents030106 microbiologyCD4-CD8 RatioEmtricitabineSettore MED/17 - MALATTIE INFETTIVENO03 medical and health sciencesCD4/CD8 ratioInternal medicineLinear regressionmedicineHumansDual therapyTenofovirbusiness.industrylcsh:RAnti-HIV AgentCD8CD8-Positive T-LymphocyteMonotherapyConfidence intervalRegimenCD4/CD8 ratio; CD8; Chronic inflammation; Dual therapy; MonotherapyCD8; CD4/CD8 ratio; Chronic inflammation; Monotherapy; Dual therapyCohort StudiebusinessCD8
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Efficacy and tolerability of switching to a dual therapy with darunavir/ritonavir plus raltegravir in HIV-infected patients with HIV-1 RNA ≤50 cp/…

2017

Background: Nucleos(t)ide reverse transcriptase inhibitors (NRTI) toxicity may represent a threat for long-term success of combined antiretroviral therapy. Some studies have suggested a possible improvement of NRTI-related toxicity after switching to NRTI-sparing regimens. Objectives: We aimed to explore the efficacy and tolerability of switching to darunavir/ritonavir (DRV/r) plus raltegravir (RAL) while having a viral load (VL) ≤50 copies/mL in the clinical setting. Study design: Treatment-experienced HIV 1-infected patients enrolled in the ICONA Foundation Study cohort were included if they switched their current regimen to DRV/r + RAL with a HIV-RNA ≤50 copies/mL. Different defin…

0301 basic medicineMaleHIV InfectionsAntiretroviral therapy; Darunavir/ritonavir; Efficacy; NRTI-sparing regimen; Raltegravir; Tolerability; Microbiology (medical); Infectious DiseasesAntiretroviral therapy; Darunavir/ritonavir; Efficacy; NRTI-sparing regimen; Raltegravir; Tolerability; Adult; Anti-HIV Agents; Cohort Studies; Darunavir; Drug Therapy Combination; Female; HIV Infections; HIV-1; Humans; Italy; Male; Middle Aged; RNA Viral; Raltegravir Potassium; Ritonavir; Viral LoadGastroenterologyCohort StudiesAntiretroviral therapy; Darunavir/ritonavir; Efficacy; NRTI-sparing regimen; Raltegravir; Tolerability0302 clinical medicineMedicineNRTI-sparing regimen030212 general & internal medicineViralDarunavireducation.field_of_studyLamivudineGeneral MedicineMiddle AgedViral LoadTolerabilityAntiretroviral therapyInfectious DiseasesTolerabilityItalyCombinationRNA ViralDrug Therapy CombinationFemaleViral loadmedicine.drugAdultMicrobiology (medical)medicine.medical_specialtyEfficacyAnti-HIV Agents030106 microbiologyPopulationDarunavir/ritonavir; Raltegravir; Efficacy; Tolerability; Antiretroviral therapy; NRTI-sparing regimenSettore MED/17 - MALATTIE INFETTIVELower riskNO03 medical and health sciencesDrug TherapyInternal medicineRaltegravir PotassiumHumanseducationDarunavirRitonavirbusiness.industryDarunavir/ritonavirRaltegravirRaltegravirHIV-1RNARitonavirbusinessAntiretroviral therapy; Darunavir/ritonavir; Efficacy; NRTI-sparing regimen; Raltegravir; Tolerability;
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Incidence and risk factors for liver enzyme elevation among naive HIV-1-infected patients receiving ART in the ICONA cohort

2019

AbstractObjectivesTo evaluate the incidence and risk factors for liver enzyme elevations (LEE) in patients initiating first-line ART in the ICONA prospective observational cohort, between June 2009 and December 2017.Patients and methodsIn total, 6575 ART-naive patients were selected, initiating two NRTIs with the third drug being a boosted PI (n=2436; 37.0%), an NNRTI (n=2384; 36.3%) or an integrase strand transfer inhibitor (INSTI) (n=1755; 26.7%). HBV surface antigen and HCV RNA were detected in 3.9% and 5.8% of the study population. Inverse probability weighted Cox regression analysis was used to calculate the HRs, according to first-line regimen, for LEE, defined as ALT or AST increases…

0301 basic medicineMaleIntegrase inhibitorHepatitis B Surface AntigenHIV Infections0302 clinical medicineRisk Factorshivh epatitis c rna surface antigens follow-up homosexuality integrase inhibitors hepatitis b virus hepatitis b virus measurement hiv infections hepatotoxicity hepatitis c virus coinfection nucleoside reverse transcriptase inhibitors non-nucleoside reverse transcriptase inhibitors cox proportional hazards models baseline value liver enzyme raltegravirPharmacology (medical)HIV Infection030212 general & internal medicineProspective StudiesProspective cohort studyCoinfectionIncidence (epidemiology)Liver DiseaseIncidenceLiver Diseasesvirus diseasesHepatitis CMiddle AgedHepatitis CReverse Transcriptase InhibitorInfectious DiseasesCohortCoinfectionPopulation studyRegression AnalysisReverse Transcriptase InhibitorsFemalemedicine.drugHumanMicrobiology (medical)Adultmedicine.medical_specialtyAnti-HIV AgentsRegression AnalysiNO03 medical and health sciencesInternal medicinemedicineHumansHIV Integrase InhibitorsHIV Protease InhibitorPharmacologyHepatitis B Surface Antigensbusiness.industryAnti-HIV AgentHIV ARTHIV Protease Inhibitorsmedicine.diseaseRaltegravir030112 virologyHIV Integrase InhibitorProspective StudieHIV-1businessAdult Anti-HIV Agents Coinfection Female Hepatitis B Surface Antigens Hepatitis C HIV Infections HIV Integrase Inhibitors HIV Protease Inhibitors HIV-1 Humans Incidence Liver Diseases Male Middle Aged Prospective Studies Regression Analysis Reverse Transcriptase Inhibitors Risk Factors
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Evolution of transmitted HIV-1 drug resistance and viral subtypes circulation in Italy from 2006 to 2016

2018

Objectives: The aim was to evaluate the evolution of transmitted HIV-1 drug resistance (TDR) prevalence in antiretroviral therapy (ART)-naïve patients from 2006 to 2016. Methods: HIV-1 sequences were retrieved from the Antiviral Response Cohort Analysis (ARCA) database and TDR was defined as detection of at least one mutation from the World Health Organization (WHO) surveillance list. Results: We included protease/reverse transcriptase sequences from 3573 patients; 455 had also integrase sequences. Overall, 68.1% of the patients were Italian, the median CD4 count was 348 cells/μL [interquartile range (IQR) 169–521 cells/μL], and the median viral load was 4.7 log 10 HIV-1 RNA copies/mL (IQR …

0301 basic medicineMaleantiretroviral therapy; HIV; recent HIV infection; resistance epidemiology; transmitted HIV drug resistance; Adult; Anti-HIV Agents; CD4 Lymphocyte Count; Female; HIV Infections; HIV-1; Humans; Italy; Male; Middle Aged; Mutation; Odds Ratio; Prevalence; Viral Proteins; Drug Resistance Viralantiretroviral therapy; HIV; recent HIV infection; resistance epidemiology; transmitted HIV drug resistance; Health Policy; Infectious Diseases; Pharmacology (medical)Drug ResistanceHIV InfectionsDrug resistanceGastroenterologyInterquartile rangeOdds RatioPrevalenceHIV InfectionPharmacology (medical)ViralbiologyHealth PolicyMiddle AgedIntegraseInfectious DiseasesItalyFemaleViral loadHumanresistance epidemiologyAdultmedicine.medical_specialtytransmitted HIV drug resistanceAnti-HIV AgentsHIV; antiretroviral therapy; recent HIV infection; resistance epidemiology; transmitted HIV drug resistance030106 microbiologyantiretroviral therapySettore MED/17 - MALATTIE INFETTIVEVirus03 medical and health sciencesrecent HIV infectionViral ProteinsInternal medicineDrug Resistance ViralmedicineViral ProteinHumansbusiness.industryAnti-HIV AgentHIVOdds ratioReverse transcriptaseConfidence intervalCD4 Lymphocyte CountMutationbiology.proteinHIV-1business
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The purine analogues abacavir and didanosine increase acetaminophen-induced hepatotoxicity by enhancing mitochondrial dysfunction

2016

Background NRTIs are essential components of HIV therapy with well-documented, long-term mitochondrial toxicity in hepatic cells, but whose acute effects on mitochondria are unclear. As acetaminophen-induced hepatotoxicity also involves mitochondrial interference, we hypothesized that it would be exacerbated in the context of ART. Methods We evaluated the acute effects of clinically relevant concentrations of the most widely used NRTIs, alone or combined with acetaminophen, on mitochondrial function and cellular viability. Results The purine analogues abacavir and didanosine produced an immediate and concentration-dependent inhibition of oxygen consumption and complex I and III activity. Th…

0301 basic medicineMicrobiology (medical)Mitochondrial DiseasesstavudineAnti-HIV Agentsantiretroviral therapyPurine analogueContext (language use)Mitochondria LiverMitochondrionPharmacologymedicine.disease_causeacute liver-failureCell Line03 medical and health sciencesOxygen ConsumptionmedicineHumansPharmacology (medical)Reverse-transcriptase inhibitorsAcetaminophenPharmacologychemistry.chemical_classificationmechanismsReactive oxygen speciesbusiness.industryassociationtoxicityAnalgesics Non-Narcoticmedicine.diseaseGlutathioneReactive Nitrogen SpeciesDideoxynucleosideshep3b cellsAcetaminophenMitochondrial toxicityDidanosine030104 developmental biologyInfectious DiseaseschemistryElectron Transport Chain Complex ProteinsToxicityhypersensitivityChemical and Drug Induced Liver Injurybusinesshepatic cellsOxidative stressmedicine.drug
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p53 and p53-related mediators PAI-1 and IGFBP-3 are downregulated in peripheral blood mononuclear cells of HIV-patients exposed to non-nucleoside rev…

2019

The improved effectiveness and safety of the combined antiretroviral therapy (cART) has largely diminished mortality and AIDS-defining morbidity of HIV-patients. Nevertheless, chronic age-related diseases in these individuals are more common and their underlying pathogenic mechanisms of these actions seem to involve accelerated aging and enhanced inflammation. The present study explores markers of these processes in a heterogenous Spanish HIV cohort using peripheral blood samples of HIV-patients and matched uninfected controls. We isolated periheral blood mononuclear cells (PBMCs) and i) compared the expression of a panel of 14 genes related to inflammation and senescence in PBMCs of HIV-pa…

0301 basic medicineSenescenceAdultMaleAnti-HIV Agents030106 microbiologyDown-RegulationInflammationHIV InfectionsCCL2Peripheral blood mononuclear cell03 medical and health sciencesVirologyAntiretroviral Therapy Highly ActivePlasminogen Activator Inhibitor 1medicineCXCL10HumansCellular SenescencePharmacologyInflammationbusiness.industryInterleukin-6Interleukin-18virus diseasesMiddle AgedCCL20Chemokine CXCL10030104 developmental biologyInsulin-Like Growth Factor Binding Protein 3ImmunologyLeukocytes MononuclearReverse Transcriptase InhibitorsInterleukin 18Tumor necrosis factor alphaFemalemedicine.symptomTumor Suppressor Protein p53businessAntiviral research
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