Aging and Antiretroviral Neurotoxicity Scott Letendre, M.D.
|
|
|
- Gordon Thompson
- 6 years ago
- Views:
Transcription
1 Aging and Antiretroviral Neurotoxicity Scott Letendre, M.D. Professor of Medicine and Psychiatry University of California, San Diego
2 Disclosures Research funds were paid to UC San Diego on behalf of Dr. Letendre: National Institutes of Health Gilead Sciences ViiV Healthcare Dr. Letendre was paid for an advisory board: ViiV Healthcare Dr. Letendre was paid for a lecture: None
3 Several ART Drug Characteristics Can Influence CNS Effectiveness Suppression of HIV Replication Lymphocytes Monocytes & Macrophages Barrier to Resistance Viral Protein Inhibition Immune Recovery Potency Metabolism & Distribution Long Half-Life Protein Binding Lipophilicity Molecular Weight Molecular Transporters Off Target Effects Neurotoxicity Direct Neurotoxicity Indirect Neurotoxicity
4 Conceptual Construct for Worsened Neurotoxicity with Aging Letendre et al, Copyright 217
5 Conceptual Construct for Worsened Neurotoxicity with Aging Letendre et al, Copyright 217
6 Conceptual Construct for Worsened Neurotoxicity with Aging Letendre et al, Copyright 217
7 Conceptual Construct for Worsened Neurotoxicity with Aging Letendre et al, Copyright 217
8 Neurotoxicity in Neuronal Culture Fetal rat cortical neurons exposed to increasing ART concentrations All drugs caused Injury Dose-effect curves and toxicity indices were calculated Neuronal Shrinkage Robertson et al, J Neurovirol 212, 18:
9 ART Drugs, Neuronal Calcium Flux, & Mitochondrial Potential Minutes Robertson et al, J Neurovirol 212, 18:
10 Efavirenz, Mitochondrial Respiration, and Neurotoxic Metabolites Funes et al, JAC 215; 7: Tovar-y-Romo et al, JPET 212, 343(2):
11 Neurotoxicity Screening of ART Drugs With Human ipsc-derived Neurons Hinckley et al, CROI 216, Abstract 395
12 Higher NRTI Levels in CNS May Increase Mitochondrial and Telomere Toxicity Reynoso et al, J Virol 212; 86(19):1327 Torres & Lewis, Laboratory Investigation (214) 94, Tenofovir was the most potent inhibitor of telomerase activity Leeansyah et al, JID 213; 27:1157
13 Amyloid-β, Microglial Cell-Associated Amyloid-β (% Control) ART Drugs Can Increase Amyloid-β & Reduce Microglial Phagocytosis EFV Reduces Microglial Phagocytosis of Aβ TC AZT 3TC AZT EFV EFV Ctrl Giunta et al, Molecular Brain 211, 4:23 Brown et al, PLoS ONE 214, 9(4): e955
14 Evidence of Neurotoxicity in Macaques and Rodents Akay-Espinoza et al, J. Neurovirol. (214) 2:39 53 cart = AZT + SQV/r
15 More in vitro and Animal Evidence than Human Evidence Underwood et al, AIDS 215, 29:
16 Greater Efavirenz Exposure is Associated with Worse Outcomes Risk Factor Odds Ratio P Value Age (per 1 years) Education (per 1 year).85.2 Non-Italian Born Efavirenz use 4..8 Ciccarelli et al, Neurology 211, 76: 143 Haas et al, AIDS 24, 18: Ma et al, CROI 215, Abstract 444
17 Protease Inhibitors & NRTIs Protease Inhibitors NRTIs LaBounty et al, HIV Medicine 216, 17(7): Ma et al, CROI 215, Abstract 444 Marcus et al, JAIDS 216; 71: Soontornniyomkij et al, AIDS 214, 28: Sakoda et al, JAIDS 217; 74(3):
18 Vascular and Metabolic Disease Increase Risk for Neurocognitive Impairment 292 HIV+ adults in the START study Prior CVD was associated with NCI Wright et al. Neurology 21; 75: HIV+ adults in the CHARTER study Diabetes and waist circumference were associated with NCI McCutchan et al. Neurology : 485 Risk OR p Prior CVD Yes Total cholesterol Higher AIDS No.41.8 Race Black Risk OR p AIDS Yes Diabetes Yes Waist circumference Larger Triglycerides Lower.32.9 BMI Smaller.69.4
19 Metabolic Syndrome Linked to Longer Durations of ART *Associations were present after adjustment for age, gender, smoking, family history, baseline plasma viral load, and CD4 Wu et al, J Antimicrob Chemother 212; 67: 11 19
20 Brain Insulin Resistance Worsens with Age Kullmann et al, Physiol Rev 216, 96: Ott et al, Diabetes, Obesity and Metabolism 212, 14:
21 C/I Insulin Molar (pmol/l) Ratio (C:I) C/I Molar Ratio (C:I) LDL/HDL (mg/dl) Ratio Insulin (pmol/l) * * Neurocognitive Decline Associated CHARTER MACS *** eclining eclining (ng/ml)8 Cholesterol (mg/dl) C-peptide (ng/ml)8 Triglycerides Cholesterol (mg/dl) TC/HDL Ratio C-peptide *** ** * eclining eclining LDL (mg/dl) LDL (mg/dl) Insulin (pmol/l) HDL (mg/dl) Insulin (pmol/l) C/I Molar Ratio (C:I) LDL (mg/dl) Adiponectin (ug/ml) HDL LDL (mg/dl) LDL/HDL C/I Molar Ratio Ratio (C:I) ** ** * eclining eclining C C with Reduced 4 Insulin * Sensitivity ** 4 4 * TC/HDL Ratio (ng/ml)8 (ng/ml)8 TC/HDL C-peptide Ratio C-peptide Cholesterol (mg/dl) TC/HDL Ratio Triglycerides TC/HDL (mg/dl) Ratio ** ** Cholesterol (mg/dl) 3 * * ** LDL/HDL Ratio C/I Molar Ratio (C:I) LDL/HDL Ratio HDL C/I (mg/dl) Molar Ratio (C:I) eclining C/ C/ * LDL/HDL ratio Adiponectin LDL/HDL (ug/ml) ratio * 1 * HDL (mg/dl) * ** Declinin Declinin Khuder et al, CROI 218, Submitted D eclinin
22 Lipids May Influence BBB Permeability, Which May Alter CNS Drug Distribution Letendre et al, 18 th CROI, 211, Abstract 48 Unpublished CHARTER Data
23 Aging and Drug Binding Proteins Veering et al, Br. J. Clin. Pharma, 199, 29, Woo et al, Clinical Biochemistry, 1994, 27(4):
24 ART Drug Concentrations in Brain Tissue: Regional Variation, CSF Comparability n Overall Mean WM mean (ng/ml) GP mean (ng/ml) CGM mean (ng/ml) CSF (ng/ml) Concentrations Similar to Historical CSF Concentration Atazanavir (ATV) 2 < 25 < 25 < 25 < Efavirenz (EFV) Emtricitabine (FTC) Lamivudine (3TC) Concentrations in White Matter Higher than Historical CSF Concentration Lopinavir (LPV) < 25 < Concentrations Higher than Historical CSF Concentration Tenofovir (TDF) WM = White Matter; GP = Globus Pallidus (Deep Gray Matter); CGM = Cortical Gray Matter Across all drugs, concentrations were lower in CGM than in the other two regions (p=.1, paired signed rank test) Bumpus et al, CROI 215, Abstract Best et al, AIDS 29; 23:83; 2 Best et al, JAC. 211; 66:354; 3 Calcagno et al, AIDS. 211; 25:1437; 4 Haas et al, ARHR. 2; 16:1491; 5 Capparelli et al, AIDS. 25; 19: 949; 6 Best et al, JAIDS. 212; 59: 376
25 Greater Than Expected Dolutegravir Intolerance in Holland Total (N=387) ART Naive (n=65) ART Experienced (n=322) Sleep Disturbance 19 (4.9%) 5 (7.7%) 14 (4.3%) Gastrointestinal 18 (4.6%) 4 (6.2%) 19 (5.9%) Neuropsychiatric 12 (3.1%) 3 (4.6%) 9 (2.8%) Fatigue 9 (2.3%) 1 (1.5%) 8 (2.5%) Headache 8 (2.1%) (%) 8 (2.5%) Paresthesias 6 (1.6%) (%) 6 (1.9%) Other 6 (1.6%) 2 (3.1%) 4 (1.2%) Overall 62 of 387 (16%) discontinued dolutegravir 56 of 62 these (9.3%) discontinued due to adverse events These 56 had 78 adverse events: 54 (69.2%) were nervous system-related van den Berk et al, CROI 216, Abstract 948
26 CNS Safety Data from Dolutegravir Clinical Trials SPRING-1 1 SPRING-2 2 FLAMINGO 3 SINGLE 4 DTG EFV DTG RTG DTG DRV/r DTG EFV n=51 n=5 n=411 n=411 n=242 n=242 n=357 n=362 Headache 1% 4% 14% 13% 17% 11% 6% 7% Dizziness 6% 18% 6% 6% 6% 5% 7% 33% Insomnia 6% 1% 6% 5% 8% 7% 1% 6% Depression * * 6% 5% 6% 4% ** ** Anxiety * * 4% 5% 5% 4% ** ** Abnormal Dreams * * ** ** ** ** 7% 16% * < 3% ** < 5% All data are from 96 weeks 1 Stellbrink et al, AIDS 213, 27: Raffi et al, Lancet 213, 13: Molina et al, Lancet HIV 215; 2: e Walmsley et al, JAIDS 215, 7:
27 CNS Safety Data from Elvitegravir Clinical Trials Study 12 1 Study 13 2 STRATEGY- NNRTI 3 STRATEGY- PI 4 EVG/c EFV EVG/c ATV/r EVG/c NNRTI EVG/c PI/r n=348 n=352 n=353 n=355 n=291 n=143 n=293 n=14 Headache 16% 11% 17% 15% 1% 3% 6% 6% Dizziness 7% 26% * * ** ** ** ** Insomnia 11% 16% * * 6% 5% 3% 5% Depression 12% 14% 1% 12% ** ** 4% 6% Anxiety * * * * ** ** 6% 4% Abnormal Dreams 15% 28% * * ** ** ** ** Back Pain * * 12% 5% ** ** ** ** * < 1% ** < 5% 1 Zolopa et al, JAIDS 213, 63: Rockstroh et al, JAIDS 213, 62: Pozniak et al, Lancet Inf Dis 214; 14: Arribas et al, Lancet Inf Dis 214, 14:
28 Dolutegravir concentration (ng/ml) Dolutegravir, Age, Sleep, & Mood 5 4 Courtesy Andrea Calcagno and Marta Boffito > 6 (95% CI) < 5 (95% CI) Cmax Time (hours) Pittsburgh Sleep Quality Index C max AUC -24 Duration of sleep (n=36).33 (.5).353 (.3) Sleep disturbance (n=38) -.1 (.55) (.47) Sleep latency (n=37) (.14) -.53 (.75) Day dysfunction (n=37) (.28) -.26 (.22) Sleep efficiency (n=35).12 (.49).32 (.86) Sleep quality (n=38) (.2).27 (.21) Medication (n=37).16 (.92).21 (.9) PSQI total (n=32).74 (.69) -.42 (.82) Elliot et al, 18th International Workshop on Clinical Pharmacology of Antiviral Therapy, 217 Borghetti et al, Italian Conference on AIDS and Antiviral Research, 217
29 Women Have Different Exposure of Some Antiretrovirals Than Men Reviews of ART pharmacokinetics indicate that women may have higher exposure of some drugs Difference exists for: Zidovudine Lamivudine Ritonavir-Boosted PIs Mixed data for nonnucleoside RTIs Floridia et al, Pharmacological Research 28, 58: Ofotokun et al, Gender Medicine, 27, 4(2):16-19
30 Pharmacogenomics May Also Influence Drug Distribution into the CNS CYP2B6 516 (rs ) ABCB (rs145642) Ma et al, CROI 216, Abstract 446
31 Nicotine and Cannabis Use May Also Affect the Blood-Brain Barrier CSAR (rho) Age (rho) Cotinine Levels (ES) Endothelial Adhesion (higher=more (higher= (older) Molecules permeable) user) Plasma VCAM1.23*.37** -.27 Plasma PECAM Plasma se-selectin ** CSF VCAM1.41**.38** -.22 CSF PECAM Basement Membrane Proteins Plasma MMP **.29 Plasma MMP-7.2.4**.9 Plasma TIMP **.7* Plasma TIMP CSF MMP-2.35** CSF MMP-7.36**.33** -.27 CSF TIMP-1.58**.16.99** CSF TIMP-2.52** Tight Junction Proteins Plasma Occludin -.32* Plasma ZO **.15 CSF Claudin-1.31**.13.8 CSF Claudin-5.23* CSF ZO Letendre et al, Preliminary Data, 217
32 Conceptual Construct for Worsened Neurotoxicity with Aging Letendre et al, Copyright 217
33 UC San Diego Igor Grant Ronald J. Ellis Robert Heaton J. Allen McCutchan Brookie Best Edmund Capparelli Cris Achim Florin Vaida CHARTER or NNTC Todd Hulgan Asha Kallianpur David Clifford Justin McArthur Ned Sacktor Ann Collier Acknowledgements Study Volunteers Tom Marcotte Davey Smith David Moore Jennifer Marquie Eliezer Masliah Debra Rosario Mariana Cherner Steven P. Woods Christina Marra Susan Morgello David Simpson Ben Gelman Donald Franklin National Institutes of Health Mental Health Drug Abuse Allergy and Infectious Diseases Trainees Bert Anderson (Emory) Qing Ma (Buffalo) Jenny Iudicello Josue Perez Santiago Raeanne Moore
34
Safety of Current Antiretroviral Therapy on the CNS Scott Letendre, M.D.
Safety of Current Antiretroviral Therapy on the CNS Scott Letendre, M.D. Professor of Medicine and Psychiatry University of California, San Diego Disclosures Research funds were paid to UC San Diego on
HIV & Women: Neurological Issues
HIV & Women: Neurological Issues Scott Letendre, M.D. Professor of Medicine University of California, San Diego 1 Do women differ from men in their risk for neurocognitive and mood disorders? 2 As the
HIV DISEASE! Neurobehavioral! Neuromedical. Igor Grant, MD, FRCP(C) Director HIV Neurobehavioral Research Program University of California, San Diego
Igor Grant, MD, FRCP(C) Director HIV Neurobehavioral Research Program University of California, San Diego HIV DISEASE! Neuromedical Neurobehavioral! HIV Neurobehavioral Disturbances HIV Associated Neurocognitive
Distribution and Effectiveness of Antiretrovirals in the Central Nervous System
Distribution and Effectiveness of Antiretrovirals in the Central Nervous System Scott Letendre, MD Associate Professor of Medicine HIV Neurobehavioral Research Center and Antiviral Research Center University
HIV and Aging: Optimizing Neurocognitive Function Scott Letendre, MD
HIV and Aging: Optimizing Neurocognitive Function Scott Letendre, MD Professor of Medicine and Psychiatry University of California, San Diego San Diego, California Disclosures Research funds were paid
The Impact of HIV and Aging on the Brain Scott Letendre, M.D.
The Impact of HIV and Aging on the Brain Scott Letendre, M.D. Professor of Medicine and Psychiatry University of California, San Diego Disclosures Research funds were paid to UC San Diego on behalf of
HIV and the Central Nervous System Impact of Drug Distribution Scott L. Letendre, MD. Professor of Medicine University of California, San Diego
HIV and the Central Nervous System Impact of Drug Distribution Scott L. Letendre, MD Professor of Medicine University of California, San Diego Disclosures Grant/research support Abbvie Gilead Sciences
Management of Neurocognitive Impairment in HIV+ Adults
Management of Neurocognitive Impairment in HIV+ Adults Scott Letendre, M.D. Professor of Medicine and Psychiatry University of California, San Diego Disclosures Research funds were paid to UC San Diego
CNS Toxicity of Integrase Inhibitors Myth or Reality? Ignacio Pérez Valero Unidad de VIH. Hospital U. La Paz
CNS Toxicity of Integrase Inhibitors Myth or Reality? Ignacio Pérez Valero Unidad de VIH. Hospital U. La Paz Question for the audience Do you think that any integrase inhibitor drug produce CNS adverse
Central Nervous System Penetration of ARVs: Does it Matter?
NORTHWEST AIDS EDUCATION AND TRAINING CENTER Central Nervous System Penetration of ARVs: Does it Matter? Christina M. Marra, MD Neurology and Medicine (Infectious Diseases) University of Washington 15
The next generation of ART regimens
The next generation of ART regimens By Gary Maartens Presented by Dirk Hagemeister Division of Clinical Pharmacology UNIVERSITY OF CAPE TOWN IYUNIVESITHI YASEKAPA UNIVERSITEIT VAN KAAPSTAD Current state
HIV Associated Neurocognitive Disorders in the era of modern CART
HIV Associated Neurocognitive Disorders in the era of modern CART Igor Grant, MD, FRCP(C) Director HIV Neurobehavioral Research Program University of California, San Diego Points to be covered HIV associated
HIV in the Brain MANAGING COMORBIDITIES IN PATIENTS WITH HIV
HIV in the Brain MANAGING COMORBIDITIES IN PATIENTS WITH HIV Shibani S. Mukerji MD, PhD Massachusetts General Hospital, Division of Immunologic, Inflammatory and Infectious Neurological Diseases Dana-Farber
STRIBILD (aka. The Quad Pill)
NORTHWEST AIDS EDUCATION AND TRAINING CENTER STRIBILD (aka. The Quad Pill) Brian R. Wood, MD Medical Director, NW AETC ECHO Assistant Professor of Medicine, University of Washington Presentation prepared
Efavirenz vs dolutegravir for 1st line ART: Is it time to change? The argument AGAINST. Graeme Meintjes University of Cape Town
Efavirenz vs dolutegravir for 1st line ART: Is it time to change? The argument AGAINST Graeme Meintjes University of Cape Town Benefits of dolutegravir Superior efficacy in SINGLE trial Side effect profile
HIV - Therapy Principles
HIV - Therapy Principles Manuel Battegay and Christine Katlama Basel, Switzerland and Paris, France Disclosure MB has received honoraria for advisory board participation from Gilead, MSD, Pfizer, ViiV
Dr Alan Winston. Imperial College Healthcare NHS Trust London. 7-8 October 2010, Queen Elizabeth II Conference Centre, London.
BHIVA AUTUMN CONFERENCE 2010 Including CHIVA Parallel Sessions Dr Alan Winston Imperial College Healthcare NHS Trust London 7-8 October 2010, Queen Elizabeth II Conference Centre, London BHIVA AUTUMN CONFERENCE
HIV associated CNS disease in the era of HAART
HIV associated CNS disease in the era of HAART CSF/CNS penetration and efficacy Acknowledgements Peter Portegies Department of Neurology, AMC Mark van der Valk Department of Internal Medicine/Infectious
Central Nervous System Complications of Hepatitis C Scott Letendre, M.D.
Central Nervous System Complications of Hepatitis C Scott Letendre, M.D. Professor of Medicine and Psychiatry University of California, San Diego Disclosures Research funds were paid to UC San Diego: National
The use of antiretroviral agents during pregnancy in Canada and compliance with North-American guidelines
The use of antiretroviral agents during pregnancy in Canada and compliance with North-American guidelines I. Boucoiran, T. Lee, K. Tulloch, L. Sauve, L. Samson, J. Brophy, M. Boucher and D. Money For and
Pharmacological considerations on the use of ARVs in pregnancy
Pharmacological considerations on the use of ARVs in pregnancy 11 th Residential Course on Clinical Pharmacology of Antiretrovirals Torino, 20-22 January 2016 Prof. David Burger, PharmD, PhD david.burger@radboudumc.nl
Fat redistribution on ARVs: dogma versus data
Fat redistribution on ARVs: dogma versus data Gary Maartens Division of Clinical Pharmacology UNIVERSITY OF CAPE TOWN IYUNIVESITHI YASEKAPA UNIVERSITEIT VAN KAAPSTAD Half of what we are going to teach
Antiretroviral Treatment 2014
Activity Code FM285 Antiretroviral Treatment 2014 Rajesh Gandhi, MD Masssachusetts General Hospital Disclosures: Educational grants to my institution from Janssen, Viiv, Abbott Learning Objectives Upon
Crafting an ART Regimen for Initiation or Salvage: Are NRTI s Necessary?
NORTHWEST AIDS EDUCATION AND TRAINING CENTER Crafting an ART Regimen for Initiation or Salvage: Are NRTI s Necessary? Brian R. Wood, MD Assistant Professor of Medicine, University of Washington Medical
HIV Treatment Update. Awewura Kwara, MD, MPH&TM Associate Professor of Medicine and Infectious Diseases Brown University
HIV Treatment Update Awewura Kwara, MD, MPH&TM Associate Professor of Medicine and Infectious Diseases Brown University Outline Rationale for highly active antiretroviral therapy (HAART) When to start
Virological suppression and PIs. Diego Ripamonti Malattie Infettive - Bergamo
Virological suppression and PIs Diego Ripamonti Malattie Infettive - Bergamo Ritonavir-boosted PIs Boosted PIs: 3 drugs in one The intrinsic antiretroviral activity Viral suppression and high baseline
Disclosures 12/7/17. UPDATES IN HIV NEUROLOGY Felicia Chow, MD, MAS University of California, San Francisco December 7, 2017
UPDATES IN HIV NEUROLOGY Felicia Chow, MD, MAS University of California, San Francisco December 7, 2017 Disclosures I have nothing to disclose. Brain Compartment Zayyad et al. Curr HIV/AIDS Rep 2015 Clinical
Didactic Series. CROI 2014 Update. March 27, 2014
Didactic Series CROI 2014 Update Christian Ramers, MD, MPH Family Health Centers of San Diego Ciaccio Memorial Clinic Jacqueline Peterson Tulsky, MD UCSF Positive Health Program at SFGH Medical Director,
What are the most promising opportunities for dose optimisation?
What are the most promising opportunities for dose optimisation? Andrew Hill Liverpool University, UK Global Financial Crisis How can we afford to treat 15-30 million people with HIV in the future? Lowering
Real Life Experience of Dolutegravir and Lamivudine Dual Therapy As a Switching Regimen in HIVTR Cohort
Real Life Experience of Dolutegravir and Lamivudine Dual Therapy As a Switching Regimen in HIVTR Cohort Yagci-Caglayik D 1, Gokengin D 2, Inan A 3, Ozkan-Ozdemir H 4, Inan D 5, Akbulut A 6, Korten V 1,
HIV Treatment: New and Veteran Drugs Classes
HIV Treatment: New and Veteran Drugs Classes Jonathan M Schapiro, MD National Hemophilia Center Stanford University School of Medicine Rome, March 2013 Overview Many excellent antiretroviral agents are
Kimberly Adkison, 1 Lesley Kahl, 1 Elizabeth Blair, 1 Kostas Angelis, 2 Herta Crauwels, 3 Maria Nascimento, 1 Michael Aboud 1
Pharmacokinetics of Dolutegravir and Rilpivirine After Switching to the Two-Drug Regimen From an Efavirenz- or Nevirapine- Based Antiretroviral Regimen: SWORD-1 & -2 Pooled PK Analysis Kimberly Adkison,
Switching antiretroviral therapy to safer strategies based on integrase inhibitors
Switching antiretroviral therapy to safer strategies based on integrase inhibitors Dr Paddy Mallon UCD HIV Molecular Research Group UCD School of Medicine paddy.mallon@ucd.ie UCD School of Medicine & Medical
2/10/2015. Switching from old regimens. HIV treatment revision: As simple as old versus new? What is an old regimen? What is an old regimen?
Switching from old regimens David Nolan Department of Immunology, Royal Perth Hospital, Western Australia Institute for Immunology and Infectious Diseases, Murdoch University, Western Australia What is
Integrase Strand Transfer Inhibitors on the Horizon
NORTHWEST AIDS EDUCATION AND TRAINING CENTER Integrase Strand Transfer Inhibitors on the Horizon David Spach, MD Clinical Director, Northwest AETC Professor of Medicine, University of Washington Presentation
Third Agent Advantages Disadvantages. Component Tenofovir/emtricitabine (TDF/FTC) 300/200 mg (coformulated with EFV as Atripla) 1 tab once daily
Table I. Recommended and Alternative Antiretroviral Regimens (DHHS Guidelines, May 1, 2014) Recommended Regimens Nucleoside Analog Reverse Transcriptase Inhibitor (NRTI) Third Agent Advantages Disadvantages
The impact of antiretroviral drugs on renal function
The impact of antiretroviral drugs on renal function Professor Bruce Hendry Renal Medicine King s College London King s College Hospital NHS Foundation Trust 1 DISCLOSURES: BRUCE HENDRY I have received
Continuing Education for Pharmacy Technicians
Continuing Education for Pharmacy Technicians HIV/AIDS TREATMENT Michael Denaburg, Pharm.D. Birmingham, AL Objectives: 1. Identify drugs and drug classes currently used in the management of HIV infected
Friday afternoon Programme
Friday afternoon Programme Pharmacology and TDM Dr Marta Boffito Consultant Physician, C&W Resistance to new anti-retrovirals Dr Steve Taylor Consultant Physician, Birmingham HIVPA Annual Conference 2008
HIV Treatment Evolution. Kimberly Y. Smith MD MPH Vice President and Head, Global Research and Medical Strategy Viiv Healthcare
HIV Treatment Evolution Kimberly Y. Smith MD MPH Vice President and Head, Global Research and Medical Strategy Viiv Healthcare Overview of the Evolution of Antiretroviral Therapy Early Treatment 1987
Prevalence of Comorbidities among HIV-positive patients in Taiwan
Prevalence of Comorbidities among HIV-positive patients in Taiwan Chien-Ching Hung, MD, PhD Department of Internal Medicine National Taiwan University Hospital, Taipei, Taiwan % of participants Comorbidity
Principles of Antiretroviral Therapy
Principles of Antiretroviral Therapy Ten Principles of Antiretroviral Therapy Skills Building Workshop: Clinical Management of HIV Infection and Antiretroviral Therapy, 11 th ICAAP, November 21st, 2011,
First line ART Rilpirivine A New NNRTI. Chris Jack Physician, Durdoc Centre ethekwini
First line ART Rilpirivine A New NNRTI Chris Jack Physician, Durdoc Centre ethekwini Overview: Rilpirivine an option for ARV Naïve patients History Current guidelines Efficacy and Safety Tolerability /
Clinical considerations in switching antiretroviral therapy
Clinical considerations in switching antiretroviral therapy David Jilich Department of Infctious Diseases, 1st Faculty of Medicine, Charles University in Prague and Na Bulovce Hospital 4th CEE Meeting
Pharmacologic Characteristics and Delivery Options for Integrase Inhibitors
Pharmacologic Characteristics and Delivery Options for Integrase Inhibitors Courtney V. Fletcher, Pharm.D. Dean, College of Pharmacy Professor, Department of Pharmacy Practice and Division of Infectious
Clinical Management Guidelines 2012
Central American Course Monitoring and Evaluation for HIV/AIDS Policy and Program Management 1 2 3 4 Module 1 Unit 1 Clinical Management Guidelines 2012 National TB, HIV/AIDS & other STIs Programme Ministry
What's new in the WHO ART guidelines How did markets react?
WHO 2013 ARV Guidelines What's new in the WHO ART guidelines How did markets react? Dr. J. Perriëns Coordinator, HIV Technology and Commodities HIV department, WHO, Geneva When to start in adults Starting
Somnuek Sungkanuparph, M.D.
HIV Drug Resistance Somnuek Sungkanuparph, M.D. Associate Professor Division of Infectious Diseases Department of Medicine Faculty of Medicine Ramathibodi Hospital Mahidol University Adjunct Professor
Nuclear Receptors Mediated Induction of P-glycoprotein by Antiretroviral Drugs in Human Brain Microvessel Endothelial Cells
Under The Microscope: The Impact of ARTs Nuclear Receptors Mediated Induction of P-glycoprotein by Antiretroviral Drugs in Human Brain Microvessel Endothelial Cells Gary N.Y. Chan, Ph. D. Candidate Supervisor:
Miss Jane Rowlands. Chelsea and Westminster Hospital, London THIRD JOINT CONFERENCE OF BHIVA AND BASHH 2014
THIRD JOINT CONFERENCE OF BHIVA AND BASHH 2014 Miss Jane Rowlands Chelsea and Westminster Hospital, London 1-4 April 2014, Arena and Convention Centre Liverpool Multi-centre open-label study of switching
Treatment strategies for the developing world
David A Cooper National Centre in HIV Epidemiology and Clinical Research The University of New South Wales Sydney, Australia First line standard of care First line in the developing world First line failure
Criteria for Oral PrEP
Oral PrEP New Drugs Roy M. Gulick, MD, MPH Chief, Division of Infectious Diseases Professor of Medicine Weill Medical College of Cornell University New York City Safe Criteria for Oral PrEP Penetrates
ANTIRETROVIRAL TOXICITY Strategies for prevention and treatment
ANTIRETROVIRAL TOXICITY Strategies for prevention and treatment Francisco Antunes Professor da Faculdade de Medicina da Universidade de Lisboa e Director do Serviço de Doenças Infecciosas do Hospital de
Dr Manisha Yapa. Chelsea and Westminster Hospital, London. 19 th Annual Conference of the British HIV Association (BHIVA)
19 th Annual Conference of the British HIV Association (BHIVA) Dr Manisha Yapa Chelsea and Westminster Hospital, London 16-19 April 2013, Manchester Central Convention Complex The impact of switching to
Supplementary information
Supplementary information Dose-response Curve Slope Sets Class-Specific Limits on Inhibitory Potential of Anti-HIV Drugs Lin Shen 1,2, Susan Peterson 1, Ahmad R. Sedaghat 1, Moira A. McMahon 1,2, Marc
Dolutegravir-Rilpivirine (Juluca)
Dolutegravir-Rilpivirine (Juluca) David H. Spach, MD Clinical Director, MW AETC Professor of Medicine Division of Infectious Diseases University of Washington Last Updated: November 30, 2017 ANTIRETROVIRAL
Metabolic Syndrome is Associated with Neurocognitive Deficits in Persons Living with HIV
Metabolic Syndrome is Associated with Neurocognitive Deficits in Persons Living with HIV Jessica L. Montoya, Ph.D. Postdoctoral Fellow Department of Psychiatry, UC San Diego 9 th International Workshop
NeuroAIDS in the modern treatment era
NeuroAIDS in the modern treatment era Igor Grant, MD, Distinguished Professor and Chair Department of Psychiatry Director HIV Neurobehavioral Research Program University of California, San Diego NIH RFBR
Starting and Switching ART: 2016
Starting and Switching ART: 2016 Luke Jerram Rajesh T. Gandhi, M.D. Massachusetts General Hospital Harvard Medical School Disclosures: grant support from EBSCO, Gilead, Merck, Viiv Thanks to Henry Sunpath,
Antiretroviral Dosing in Renal Impairment
Protease Inhibitors (PIs) Atazanavir Reyataz hard capsules 300 mg once daily taken with ritonavir 100 mg once daily No dosage adjustment is needed for atazanavir in renal impairment Atazanavir use in haemodialysis
The Use of Integrase Inhibitors In Latin America: From Guidelines to the Real World Ernesto Martínez B., MD Internal Medicine, Infectious Diseases
De afbeelding kan niet worden weergegeven. The Use of Integrase Inhibitors In Latin America: From Guidelines to the Real World Ernesto Martínez B., MD Internal Medicine, Infectious Diseases DISCLOSURE
Clinical notes: Management of HAART in patients with HAND
Clinical notes: Management of HAART in patients with HAND Paola Cinque Dipartment of Infectious Diseases San Raffaele Scientific Institute, Milano, Italy 11 Residential Course on Clinical Pharmacology
HIV Neurology Persistence of Cognitive Impairment Despite cart
HIV Neurology Persistence of Cognitive Impairment Despite cart Victor Valcour MD PhD Professor of Medicine Memory and Aging Center, Dept. of Neurology University of California San Francisco, USA 8 th International
Efficacy and Safety of Doravirine 100mg QD vs Efavirenz 600mg QD with TDF/FTC in ART-Naive HIV-Infected Patients: Week 24 Results
Efficacy and Safety of Doravirine 1mg QD vs Efavirenz 6mg QD with TDF/FTC in ART-Naive HIV-Infected Patients: Week 24 Results Jose M. Gatell, Francois Raffi, Andreas Plettenberg, Don Smith, Joaquin Portilla,
Introduction to HIV Drug Resistance. Kevin L. Ard, MD, MPH Massachusetts General Hospital Harvard Medical School
Introduction to HIV Drug Resistance Kevin L. Ard, MD, MPH Massachusetts General Hospital Harvard Medical School Objectives 1. Describe the epidemiology of HIV drug resistance in sub-saharan Africa. 2.
Higher rates of neuropsychiatric adverse events leading to dolutegravir discontinuation in women and older patients
DOI: 10.1111/hiv.12468 ORIGINAL RESEARCH Higher rates of neuropsychiatric adverse events leading to dolutegravir discontinuation in women and older patients C Hoffmann, 1,2 T Welz, 3 M Sabranski, 1 M Kolb,
Prima linea: dovremmo evitare i PI nella terapia di prima linea per i loro effetti non desiderati? Giuseppina Liuzzi
6 th INFECtivology TOday Paestum 15-16 -17 maggio 2014 Prima linea: dovremmo evitare i PI nella terapia di prima linea per i loro effetti non desiderati? Giuseppina Liuzzi Istituto Nazionale per le Malattie
HIV and Co-morbidities November 18, 2013, 3:10 pm Abstract Number 141
Low omega-3 index in erythrocytes is a risk factor for progression of atherosclerosis in people living with HIV Bianca M Arendt, M Smieja, IE Salit, DWL Ma, F Smaill, D Elston, E Lonn, Johane P Allard
HAND is Common and Important in Patients on ART
HAND is Common and Important in Patients on ART Igor Grant, MD, FRCP(C) Director HIV Neurobehavioral Research Program University of California, San Diego How is HAND diagnosed? How prevalent is it? Points
When to Rock the Boat Switching Antiretroviral Therapy for Metabolic Complications
When to Rock the Boat Switching Antiretroviral Therapy for Metabolic Complications 12 th Annual Tennessee AETC/CCC HIV Symposium 6 November 2009 Todd Hulgan, MD, MPH Assistant Professor of Medicine Division
Comprehensive Guideline Summary
Comprehensive Guideline Summary Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents AETC NRC Slide Set Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and
INTERGRASE INHIBITORS- WHAT S NEW?
INTERGRASE INHIBITORS- WHAT S NEW? Professor Margaret Johnson Royal Free London Foundation Trust October 2018 Targeting the HIV life-cycle NEW HIV VIRON MATURATION CO-RECEPTOR BINDING FUSION BUDDING CD4
Antiretroviral Therapy: What to Start
FLOWED: 05-14-2015 Chicago, IL: May 18, 2015 Antiretroviral Therapy: What to Start Eric S. Daar, MD Professor of Medicine David Geffen School of Medicine University of California Los Angeles Los Angeles,
Department of General Medicine, Juntendo University School of Medicine, Tokyo; and 2
Jpn. J. Infect. Dis., 69, 33 38, 2016 Original Article Raltegravir and Abacavir/Lamivudine in Japanese Treatment-Naäƒve and Treatment-Experienced Patients with HIV Infection: a 48-Week Retrospective Pilot
D:A:D: Cumulative Exposure to DRV/r Increase MI Risk
D:A:D: Cumulative Exposure to DRV/r Increase MI Risk 20.0-15.0-10.0-5.0-4.0-3.0-2.0-1.0- Unadjusted CVD rate ratios per 5 years additional exposure: ATV/r 1.25 [1.10-1.43] and DRV/r 1.93 [1.63-2.28] Adjusted*
Cases from the Clinic(ians): Case-Based Panel Discussion
Cases from the Clinic(ians): Case-Based Panel Discussion Michael S. Saag, MD Professor of Medicine The University of Alabama at Birmingham EDITED: 03-12-14 Learning Objectives After attending this presentation,
Clinical Commissioning Policy: Dolutegravir for treatment of HIV-1 infection (all ages) NHS England Reference: B06/P/a
Clinical Commissioning Policy: Dolutegravir for treatment of HIV-1 infection (all ages) NHS England Reference: B06/P/a 1 2 Clinical Commissioning Policy: Dolutegravir for treatment of HIV-1 infection (all
Treatment of respiratory virus infection Influenza A & B Respiratory Syncytial Virus (RSV)
Treatment of respiratory virus infection Influenza A & B Respiratory Syncytial Virus (RSV) Amantadine and Rimantadine Use is limited to Influenza A infection. Very effective in preventing infection if
Cerebral Small Vessel Disease and HAND in ARV-treated Subjects
Cerebral Small Vessel Disease and HAND in ARV-treated Subjects Cristian L. Achim, MD, PhD Ronald J. Ellis, MD, PhD Virawudh Soontornniyomkij, MD ARROW, Bucharest, Romania October 5-6, 2015 Rationale and
Effects of cobicistat on tenofovir exposure and its long-term tolerability: is it time to rethink at TAF trials?
Effects of cobicistat on tenofovir exposure and its long-term tolerability: is it time to rethink at TAF trials? Sara Baldelli 1, Andrea Giacomelli 2, Davide Minisci 2, Cristina Mazzali 3, Laura Milazzo
Treatment update. Bronagh McBrien June 2016
Treatment update Bronagh McBrien June 2016 Speaker Name Bronagh McBrien Statement Received educational funding and support from Gilead, Merck, Boehringer Ingelheim, Janssen-Cilag Date : 27 June 2016 BHIVA
ORIGINAL CONTRIBUTION. Validation of the CNS Penetration-Effectiveness Rank for Quantifying Antiretroviral Penetration Into the Central Nervous System
ORIGINAL CONTRIBUTION Validation of the CNS Penetration-Effectiveness Rank for Quantifying Antiretroviral Penetration Into the Central Nervous System Scott Letendre, MD; Jennifer Marquie-Beck, BS; Edmund
CAB 59: HIV and neurocogni5ve impairment
HIV Neurology CAB 59: HIV and neurocogni5ve impairment Friday 8 th July 2016 Dr Nick Davies Consultant Neurologist, Chelsea & Westminster Hospital & Imperial College NHS Trust (Charing Cross Hospital),
12th European AIDS Conference / EACS ARV Therapies and Therapeutic Strategies A CME Newsletter
EACS 2009 11-14, November 2009 Cologne, Germany Course Director Jürgen K. Rockstroh, MD Co-Chairman, 12th European AIDS Conference Professor, University of Bonn Bonn, Germany Faculty Calvin Cohen, MD,
Central Nervous System Penetration and Effectiveness of Darunavir/Ritonavir Monotherapy
AIDS Rev. Ignacio 2014;16:101-8 Pérez Valero, et al.: CNS Penetration and Effectiveness of Darunavir/Ritonavir Monotherapy Central Nervous System Penetration and Effectiveness of Darunavir/Ritonavir Monotherapy
Antiviral Therapy 2018; 23:21 32 (doi: /IMP3171)
Antiviral Therapy 2018; 23:21 32 (doi: 10.3851/IMP3171) Original article Metabolic profiles of individuals switched to second-line antiretroviral therapy after failing standard first-line therapy for treatment
Optimizing 2 nd and 3 rd Line Antiretroviral Therapy in Children and Adolescents
Optimizing 2 nd and 3 rd Line Antiretroviral Therapy in Children and Adolescents Victor Musiime, MBChB, MMED, PhD Senior Lecturer, Makerere University Investigator, Joint Clinical Research Centre (JCRC)
HIV Treatment: State of the Art 2013
HIV Treatment: State of the Art 2013 Daniel R. Kuritzkes, MD Chief, Division of Infectious Diseases Brigham and Women s Hospital Professor of Medicine Harvard Medical School Success of current ART Substantial
REVIEW No Assessment of safety a. Have all relevant studies on safety been included Yes X No (if no, please provide reference and information)
Expert peer review on application for addition of fixed dose combination formulations of antiretroviral medications in the EML (Adults) REVIEW No. 2 Abacavir + lamivudine (ABC+ 3TC) Tablet (dispersible):
Lê MP, 1,2 Cournil A, 3 Kouanfack C, 4 Lem S, 5 Le Gac S, 5 Delaporte E, 3 Peytavin G, 1,2 for the NAMSAL study group
Lê MP, 1,2 Cournil A, 3 Kouanfack C, 4 Lem S, 5 Le Gac S, 5 Delaporte E, 3 Peytavin G, 1,2 for the NAMSAL study group 1 AP-HP, Hopital Bichat, Pharmacology-Toxicology, Paris, France, 2 IAME, UMR 1137,
Antiretroviral Treatment Strategies: Clinical Case Presentation
Antiretroviral Treatment Strategies: Clinical Case Presentation Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan Chia-Jui, Yang M.D Disclosure No conflicts of interests.
Clinical Commissioning Policy: Use of cobicistat (Tybost ) as a booster in treatment of HIV positive adults and adolescents
Clinical Commissioning Policy: Use of cobicistat (Tybost ) as a booster in treatment of HIV positive adults and adolescents 1 Clinical Commissioning Policy: Use of cobicistat (Tybost ) as a booster in
ART and Prevention: What do we know?
ART and Prevention: What do we know? Biomedical Issues Trip Gulick, MD, MPH Chief, Division of Infectious Diseases Professor of Medicine Weill Cornell Medical College New York City ART for Prevention:
More Options, Some Opinions Initial Therapies for HIV Judith S. Currier, MD
More Options, Some Opinions Initial Therapies for HIV Judith S. Currier, MD More Options, Some Opinions: Initial Therapies for HIV Judith S. Currier, MD University of California Los Angeles Los Angeles,
Frailty and age are independently associated with patterns of HIV antiretroviral use in a clinical setting. Giovanni Guaraldi
Frailty and age are independently associated with patterns of HIV antiretroviral use in a clinical setting Giovanni Guaraldi Potential conflicts of interest Research funding: Jansen, Gilead, MSD, BMS Consultancies:
The ART of Managing Drug-Drug Interactions in Patients with HIV
The ART of Managing Drug-Drug Interactions in Patients with HIV Bradley L. Smith, Pharm.D. smith.bradley1@mayo.edu Pharmacy Grand Rounds December 19, 2017 2017 MFMER slide-1 Presentation Objectives Describe
POST-EXPOSURE PROPHYLAXIS, PRE-EXPOSURE PROPHYLAXIS, & TREATMENT OF HIV
POST-EXPOSURE PROPHYLAXIS, PRE-EXPOSURE PROPHYLAXIS, & TREATMENT OF HIV DISCLOSURE Relevant relationships with commercial entities none Potential for conflicts of interest within this presentation none
Disclosures (last 12 months)
HIV Research What s in the Pipeline? Samir K. Gupta, MD, MS Division of Infectious Diseases Indiana University School of Medicine Disclosures (last 12 months) Independent research grant funding by NIH/NHLBI,
PHARMACOKINETICS OF ANTIRETROVIRAL AND ANTI-HCV AGENTS
8. PHARMACOKINETICS OF ANTIRETROVIRAL AND ANTI-HCV AGENTS David Burger José Moltó Table 8.1a: INFLUENCE OF FOOD ON ABSORPTION (AREA UNDER THE CURVE) OF ANTIRETROVIRAL AGENTS NUCLEOSIDE ANALOGUES NtRTI
Vitamin D Deficiency in HIV: A Shadow on Long-Term Management?
AIDS Rev. 2014;16:59-74 (Supplementary Data) Vitamin D Deficiency in HIV: A Shadow on Long-Term Management? Chloe Orkin, et al.: Vitamin D deficiency in HIV (Supplementary Data) Chloe Orkin 1, David A.