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ANTIVIRAL TREATMENT:
HERPESVIRUSES, INFLUENZA
Prof. Mojca Matičič, MD, PhD
Clinic for Infectious Diseases and Febrile IllnessesUniversity Medical Centre Ljubljana
Faculty of Medicine, University of Ljubljana
Ljubljana: April 15, 2019
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The extent of the pipelines
Antibiotics
Antivirals
Antibiotics
Antifungals
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Viral infections
• Clinical course depends on:
virus patogenity
patient immunity
• Infection: acute
chronic
latent (clinically inactive) → reactivation
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Treatment of viral infections
• Usually symptomatic
Antivirals used for:
• Treatment: for clinically overt disease
• Pre-emptive treatment: for prevention of disease in increased replication of latent viruses
• Supressive treatment: for prevention of reactivation of latent viruses© ESCMID eLibrary by a
uthor
Antiviral drugs
Viruses:
• replicate intracellulary
• to synthesize viral particles they employ: - host cell enzymes - host cell macromolecules - host cell organelles
Antiviral drugs:
• discrimination between host functions and viral functions© ESCMID eLibrary b
y author
Antiviral drugs
NO “MAGIC BULLET”
Main problems:
• toxicity
• efficacy
• resistance© ESCMID eLibrary by a
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Medications against viral infections
• Antivirals:
prevent viral replication intracellularly nucleos(t)ide analogues, protease inhibitors, integrase inhibitors etc
• Immunomodulators:
enhance or change host immune response to viruses immunoglobulins, interferons, biological therapy (anti TNF, anti-CD20, anti-CD52 etc)
• In 2019: over 50 antivirals for systemic usenew or updated giudelines for their use© ESCMID eLibrary b
y author
VIRAL INFECTIONS treated with SYSTEMIC ANTIVIRALS
Against: HIV (33)
herpesviruses: HSV-1, HSV-2, VZV, CMV
influenza viruses
hepatitis B virus (HBV), hepatitis C virus (HCV)
respiratory syntitial virus (RSV)
other viruses: EBV, HHV-6
parvo B19,
enteroviruses, adenoviruses,
human polioma viruses BK, JC
HPV© ESCMID eLibrary by a
uthor
VIRAL INFECTIONS treated with SYSTEMIC ANTIVIRALS
Against: HIV (33)
herpesviruses: HSV-1, HSV-2, VZV, CMV
influenza viruses
hepatitis B virus (HBV), hepatitis C virus (HCV)
respiratory syntitial virus (RSV)
other viruses: EBV, HHV-6
parvo B19,
enteroviruses, adenoviruses,
human polioma viruses BK, JC
HPV© ESCMID eLibrary by a
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Human herpesviruses
Common characteristics: lifelong infection
latency
reactivation
oncogeneity
NOT curable!
Clinical sindromes related to herpesvirus infections:Syndrome HSV-1 HSV-2 VZV CMV EBV HHV-6 HHV-7 HHV-8
Gingivostomatitis + + - - - - - -
Genital lesions + + - - - - - -
Keratokonjuktivitis + + + - - - - -
Retinitis + + + + - - - -
Skin lesions + + + + + + + +
Ezophagitis + + + + - - - -
Pneumonitis + + + + + + - -
Hepatitis + + + + + + - -
Meningitis + + + - + + - -
Encephalitis + + + + + + + -
Mononucleosis - - - + + + - +?
Hemolytical anemia - - + + + -
Peripartal infection + + + + - + - +
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Antiviral drugs used for herpesvirus infections
VIRUS Antivirals
HSV and VZVinhibitors
aciclovirvalaciclovirpenciclovir*famciclovir
brivudinidoksuridin*trifluridin*vidarabin*
CMVinhibitors
ganciclovirvalganciclovir
foscarnetcidofovir
fomiversen**HSV = virus herpes simplex; VZV = virus varicella-zoster; CMV = citomegalovirus
*: topical; **intravitreal
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Aciclovir
• Guanozine derivative• Patented in 1974; approved for medical use in 1981
• Oral/intravenous/topical administration
• In vitro: most potent against HSV-1half as potent against HSV-210th as potent against VZV
• Most commonly used in HSV infections
• Very well tolerated• Favourable safety profile
AE: renal disfunction
• Pregnancy: at high doses chromosomal breakageNO fetal abnormalities
NO MORE abnormalities compared to the newborns in general population
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Valaciclovir
• L-valine ester of aciclovir (prodrug form of aciclovir)
• Oral administration
• Enhanced absorbtion after oral administration
• Bioavailability: 3-5x ↑ compared to acyclovir
• Concentration-time curve:
1g tid PO valcyclovir = 5 mg/kg tid IV acyclovir
• Very well tolerated
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• Guanosine analogue
• Prodrug form of penciclovir with improved oral bioavailability (77%↑)
• Oral administration
• Intracellular concentrations of penciclovir triphosphate are higher than acyclovir triphosphate
• Penciclovir is not metabolized, but is eliminated unchanged in urine
• Adjustment of the famciclovir dose is required in patients with creatinine clearance of <60 ml/min.
Famciclovir
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Brivudin
IC50 activity in vitro
• Bromovinildeoksiuridin
• Competitive inhibitor of viral DNA polymerase
• Oral administration
• Once daily
• In vitro:
BVD 200-1000 times more potent in inhibition of VZV replicationcompared to ACV
• Indication: Shingles
in immunocompetent patients© ESCMID eLibrary by a
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Brivudin
IC50 activity in vitro
• Bromovinildeoksiuridin
• Competitive inhibitor of viral DNA polymerase
• Oral administration
• Once daily
• In vitro:
BVD 200-1000 times more potent in inhibition of VZV replication compared to ACV
• Indication: Shingles in immunocompetent patients
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HSV infectionsSystemic treatment options
• acyclovir
• valacyclovir
• famciclovir
Rescue treatment:
• foscarnet
• cidofovir
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HSV-1, HSV-2Systemic antiviral treatment efficacy
• Primary: acyclovir IV/PO speeds healing of lesions valacyclovir PO reduces virus shedding
• Recurrent:acyclovir PO speeds healing of lesionsvalacyclovir PO
• Immunocompromised:speeds healing of lesions
acyclovir IV
reduces virus shedding
• Labial herpes:valacyclovir 2g bid, 1 day reduces duration by 1 day
Fife KH. Sex Transm Dis 1997; 24: 481-6. Bodsworth NJ. Genitourin Med 1997: 73: 110-6.
CDC. MMWR 2010; 59(RR-12): 15-6.
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HSV-1, HSV-2Indications for systemic TREATMENT
• genitalni herpes: primary infection recurrences
• orofacialni herpes • ophtalmic herpes• herpes encephalitis• neonatal herpes• mucocutaneous herpes in immunocompromised • Other herpetic syndromes
eccema herpeticum, erythema multiforme hepatitis, proctitis, esophagitis, pneumonitis systemic infection
GPs
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HSV-1, HSV-2Indications for systemic TREATMENT
• genitalni herpes: primary infection recurrences
• orofacialni herpes • ophtalmic herpes• herpes encephalitis• neonatal herpes• mucocutaneous herpes in immunocompromised • Other herpetic syndromes
eccema herpeticum, erythema multiforme hepatitis, proctitis, esophagitis, pneumonitis systemic infection© ESCMID eLibrary b
y author
Genital herpesIndications for CHEMOPROPHYLAXIS
• Immunocompetent patients:
recurrent herpes (≥6 recurrences per year)
• Immunodefficient patients:
recurrent herpes solid organ/bone marrow Tx
HIV/aidshaematological malignances© ESCMID eLibrary b
y author
Treatment regimens for HSV infection
HSV
encephalitis aciclovir intravenous 10-15 mg/kg x 3; 14-21 daysimmunocompromised–
systemic infectionsaciclovir intravenous 10-15 mg/kg x 3; 14-21 days
neonatal herpes aciclovir intravenous 10-15 mg/kg x 3; 14-21 days
genital herpes
primary
(treatment)
aciclovir orintravenous 5 mg/kg x 3; 5-10 days
oral 200 mg x 5; 7-10 days
valaciclovir or oral 500 mg x 2; 7-10 days
famciclovir oral 250 mg x 3; 7-10 days
recurrent
(treatment)
aciclovir or oral 200 mg x 5; 5 days or
800 mg x 2; 5 days
valaciclovir or oral 500 mg x 2; 3 days
famciclovir oral 1000 mg x 2; 1 days
recurrent
(chemo-
prophylaxis)
aciclovir or oral 200 mg x 1-5 or
400 mg x 2; several months
valaciclovir or oral 500-1000 mg x 1; several months
famciclovir oral 125-250 mg x 2; several months
immuno-
compromised –
mucocutaneous
herpes
treatment
aciclovir orintravenous 5 mg/kg x 3; 7 days
oral 500 mg x 5; 10 days
valaciclovir or oral 1000 mg x 3; 7 days
famciclovir oral 500 mg x 2; 4 days
chemo-
prophylaxis
aciclovir ororal 200 mg x 2; prolonged
intravenous 5 mg/kg x 2; prolonged
valaciclovir or oral 1000 mg x 3; prolonged
famciclovir oral 500 mg x 2; prolonged
labial herpes
(recurrent)
penciclovir or topical 1% ointment: for 2h in the morning; 4 days
valaciclovir or oral 2000 mg x 2; 1 day
famciclovir oral 500 mg x 3; 5 days
herpetic keratitis
aciclovir or oral 200 mg x 5; 7-10 days
valaciclovir oral 500 mg x 2; 10 days
+
aciclovir or topical 3% ointment: 5x daily
trifluridin or topical1 gtt, 1% ocular solution:every 2 h during
daytime
vidarabin topical 3% ointment: 5xdailyTomažič J, Strle F, et al. Infekcijske bolezni. 2nd ed. Ljubljana, SZD 2017; p. 76-7.
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HSV-1, HSV-2Resistance to acyclovir
Prevalence:• immunocompetent patients: 0,3 % (USA) - 0,7 %(UK)
0,19 % (11 large trials)
• herpes keratitis patients: 6,4 %
• HIV/aids patients: 3,5-7 %
• solid organ Tx patients: 2,5-10%
• allogenic bone marrow Tx patients: 30%
Treatment options: RESCUE ONLY!
• foscarnet IV
• cidofovir IV (not well controlled studies)
Morfin F, Trouvenet J. J Clin Virol 2003; 26: 29-37. Chilukuri S, Rosen T. Dermatol Clin 2003; 21: 311-20. Pirat J, Boivin S. Antimicrobial Agents Chemother 2011; 55: 459-72.
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VZVChickenpox
Serious compications in:
• adults (50x ↑ than children)
• newborns
• immunocompromised
• pregnancy
• chronic pulmonary diseases
• chronic skin diseases© ESCMID eLibrary by a
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ChickenpoxSystemic treatment options
VZV HSV
• acyclovir : 5x800 mg PO 5-7 days 5x200mg
• acyclovir : 3x10 mg/kg IV 10 days 3x 5 mg/kg
• valacyclovir : 3x1000 mg PO 5-7 days 2x500 mg
• famciclovir
Aciclovir : VZV vs HSV
higher doses and more frequent dosing for VZV than for HSV (VZV less sensitive)
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ChickenpoxSystemic treatment efficacy
Immunocompetent host:
- children: ↓ fever duration temperature↓ no. of lesions (247 vs. 347)speeds healing (2.7 days vs. 3.2 days)
- adolescents: ↓ fever duration ↓ time of new lesion development (for 0.5 days)
- adults: ↓ fever duration (for 1.8 days)speeds healing ↓ general symptoms
Immunocompromised host:
- Systemic treatment prevents dissemination of the disease
Balfour HH, 1990; Dunkle LM, 1991; Wallace MR, 1992; Walsh JB,1996; Dunkle LM, 2001; Balfour HH, 2001.
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CHICKENPOXAvtiviral treatment guidelines
• Indications: >18 yearssecondary contacts 12-17 yearspregnant womenpatients with complicationsimmunocompromised
• Treatment should be started within 48 hours of the onset of skin lesions(except for immunocompromised patients)
• Pregnant women should be warned on Category 3 treatmentrecommendation
• Acyclovir IV in highly impaired immunity: HIV/aids, haematologicalmalignancies, high dose citostatic treatment, TX
• Acyclovir PO or valacyclovir PO in moderately impaired immunity: solidtumors, corticosteroid therapy, low dose citostatic treatment
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Treatment regimens for CHICKENPOX
Imunity Patients Antivirals Mode of application
Dosing Treatment duration
normal
<12 years symptomatic / / /
12-18 yearsprimary contact symptomatic / / /
secondary
contact
aciclovir p.o. 5x800mg 5-7days
>18 years
valaciclovir or p.o. 3x1000mg 5-7days
famciclovir or p.o. 3x500mg 5-7days
aciclovir p.o. 5x800mg 5-7days
newborns aciclovir i.v. 10mg/kg/8h 5-7days
pregnant women aciclovir p.o. 5x800mg 5-7days
complications aciclovir i.v. 10mg/kg/8h 10 days
deficient
Immune deficiency: mild /
moderate:•solid tumor in remission,
•corticoid treatment
•moderate dosing of citostatics
valaciclovir or p.o. 3x1000mg ≥7days
famciclovir or p.o 3x500mg ≥7days
aciclovir p.o 5x800mg ≥7days
Immune deficiency: severe
• HIV/aids,
•stemcell carcinoma,
•high dosing of citostatics,
•treansplant recipients
aciclovir i.v. 10mg/kg/8h 7-10days
complications aciclovir i.v. 10mg/kg/8h
aciclovir resistant viral strains foscarnet i.v. 40-60mg/kg/8h ≥14days
Tomažič J, Strle F, et al. Infekcijske bolezni. 2nd ed. Ljubljana, SZD 2017; p. 76-7.
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VZVShingles (Herpes zoster)
Complications:• Dissemination: skin
pneumonitis, hepatitis
meningo/encephalitis
• Dermatological: bacterial superinfection
granulomatous dermatitis
erythema multiforme
• Due to localisation: otic
ophtalmic
anogenital
• Postherpetic neuralgia © ESCMID eLibrary by a
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ShinglesSystemic antiviral treatment efficacy
• Shortens healing process of acute disease
• Alleviates pain
• Alleviates/prevents acute and chronic complications(postherpetic neuralgia!)
Am J Clin Dermatol 2005; 6: 317-25.
Dworkin RH. Clin Infect Dis 2007; 44: S1-26.
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ShinglesSystemic antiviral treatment
Indications: >50 years of agesevere pain/several vesicles at any age zoster on head/neckimmunocompromisedatopic dermatitiseccema
Effective: given within 48-72 hours by rash onset>72 hours: ophtalmic HZ
immunocompromisedsevere acute pain
Am J Clin Dermatol 2005; 6: 317-25.
Dworkin RH. Clin Infect Dis 2007; 44: S1-26.
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Imunity Patients AntiviralsMode of application Dosing
Treatment duration
preserved
<50 years
Pain: no / mild symptomatic / / /
Pain: moderate / severe
valaciclovir or p.o. 3x1000mg 7days
famciclovir or p.o. 3x500mg 7days
brivudin or p.o. 1x125mg 7days
aciclovir p.o. 5x800mg 7days
>50 years
valaciclovir or p.o. 3x1000mg 7days
famciclovir or p.o. 3x500mg 7days
brivudin or p.o. 1x125mm 7days
aciclovir p.o. 5x800mg 7days
Zoster ophtalmicus / zoster oticus(any age)
valaciclovir or p.o. 3x1000mg 7days
famciclovir or p.o. 3x500mg 7days
aciclovir p.o. 5x800mg 7days
deficient
Immune deficiency: mild / moderate:•solid tumor in remission,
•after immunosupressive treatment
aciclovir or p.o. 5x800mg 7days
valaciclovir or p.o. 3x1000mg 7days
famciclovir p.o 3x500mg 7days
Immune deficiency: severe
•leukemia / lymphome
•immunosupressive therapy
•trensplant recipients
aciclovir i.v. 10mg/kg/8h 7-10days
HIV/aids:•zoster in one dermatoma
(not face)
aciclovirali p.o. 5x800mg 7-10days
valaciclovir p.o. 3x1000mg 7-10days
• zoster with complications
(face, multiple dermatomas, etc)aciclovir i.v. 10mg/kg/8h 10-
14(21)days
disseminated disease aciclovir i.v. 10mg/kg/8h 10-
14(21)days
aciclovir resistant viral strains foscarnet i.v. 40-60
mg/kg/8h
≥14days
Treatment regimens for ZOSTER
Tomažič J, Strle F, et al. Infekcijske bolezni. 2nd ed. Ljubljana, SZD 2017; p. 76-7.
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CMVAntiviral treatment
DNA polymerase inhibitors:• Ganciclovir
• Valganciclovir
• Foscarnet
• Cidofovir
• Brincidofovir
Viral terminase inhibitor: NEW!• Letermovir© ESCMID eLibrary b
y author
Ganciclovir• synthetic analogue of 2′-deoxy-guanosine
• DNA polymerase inhibitor
• absorption of the oral form is very limited
• 90% of plasma ganciclovir is eliminated unchanged in the urine
• a half-life of 2–6 hours
Indication: primarily CMV (symptomatic immunocompromised pts)
Administration:
- IV
- slow-release formulations (implantate) – intravitreous
- topical ophthalmic gel (acute HSV keratitis)
AE: bone marrow supression (↓ Leu, ↓Tr)
Resistant strains: rarely occur (genes: DNA polymerase, UL97)
usually sensitive for foscarnet and cidofovir
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Valganciclovir
• L-valyln ester of gancyclovir
• Good resorbtion
• 60% bioavailability
• Oral administartion
• Indications: CMV infection
- treatment (900 mg/day bid)
symptomatic immunocompromised pts
- pre-emptive treatment (900 mg/day bid)
- chemoprophylaxis (900 mg/day qd)
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Foscarnet
• phosphonoformic acid
• DNA polymerase inhibitor
• only IV
• efficacy: same as ganciclovir
• Indication: CMV retinitis in HIV/aids pts
CMV - failure of ganciclovir (resistant virus, neutropenia)
HSV, VZV - ONLY rescue treatment !
• MAJOR TOXICITY:
renal impairment !!! (Ca, K, P, Mg)
• Cross-resistance with gancyclovir possible© ESCMID eLibrary b
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Cidofovir
• citosyne derivate
• DNA polymerase inhibitor
• only IV
• long half-life time: 5mg/kg once a week for 2 weeks
followed by maintainance 5mg/kg /2 wks
• MAJOR TOXICITY: renal impairment !!!
Indications:
• Primarily CMV
• HSV, VZV - ONLY rescue treatment
BRINCIDOFOVIR: lyposomal prodrug of CIDOFOVIR
1000x more potent than cidofovir against CMV
oral, high blood levels, NOT nephrotoxic© ESCMID eLibrary b
y author
CMV infection
prophylaxis valganciclovir oral 900 mg once daily; 3-6 mths
pre-emptive treatment
valganciclovir or
oral 900 mg x 2; untill 2 x negative viremia
ganciclovir intravenous 5 mg/kg x 2; untill 2 x negative viremia
treatment
ganciclovir or
intravenous5 mg/kg x 2; at least 14 d;Followed by maintainance 5 mg/kg/d
valganciclovir or oral900 mg x 2; at least 14 d;Followed by maintainance 900 mg/d
foscarnetor
intravenous90 mg/kg x 2 or 60 mg/kg x 3; at least 14 d;Followed by maintainance: 90-120 mg/d
cidofovir intravenous
5 mg/kg, 1 x weekly; 2 weeks;Followed by 1x per 2 weeksGood hidrationAdd probenecid
fomivirsen intravitreal1. day and 15. day: 330 mg;Followed by maintainance 330 mg /mth
Treatment regimens forCMV infection
Tomažič J, Strle F, et al. Infekcijske bolezni. 2nd ed. Ljubljana, SZD 2017; p. 76-7.
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letermovir
Existing CMV antivirals
• Existing CMV antivirals & brincidofovir are inhibitors of viral DNA polymerase
• inhibits the synthesis of viral DNA
• act early in the virus lifecycle
• Letermovir is a novel viral terminase inhibitor
• prevents proper DNA cleavage into unit-length genome and packaging of these genomes into
procapsids
• blocks viral replication without inhibiting the synthesis of HCMV DNA or viral proteins
• prevents the formation of infectious virions
• acts late in the virus lifecycle
letermovir
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EBVAntiviral treatment
• Indication: PTLD
HPS
• Treatment: ganciclovir?
rituximab?
other?© ESCMID eLibrary b
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INFLUENZA pandemics
151.700 –575.400
ECDC, 2009.
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INFLUENZA pandemics
151.700 –575.400
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INFLUENZAProportion of vaccinated persons
aged >65 years in Europe
European Centre for Disease Prevention and Control. Seasonal influenza vaccination andantiviral use in EU/EEA Member States – Overview of vaccine recommendations for 2017–2018 and vaccinationcoverage rates for 2015–2016 and 2016–2017 influenza seasons. Stockholm: ECDC; 2018.
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Amantanes - target M2 ion channel protein of influenza A virus:- Amantadine and rimantadine - active against influenza A virus (not influenza B virus!)
- high levels of resistance (>99% in H3N2 and H1N1) NOT recommended for antiviral treatment or chemoprophylaxis
Neuraminidase inhibitors - active against both influenza A and B viruses:
– oral oseltamivir phosphate (Tamiflu®)
– inhaled zanamivir (Relenza®)
– intravenous peramivir (Rapivab®)
Endonuclease inhibitor (cap-dependent):- oral baloxavir marboxil (Xofluza®) - approved 2018 in Japan, USA
INFLUENZAAntiviral agents
https://www.cdc.gov/flu/professionals/antivirals/summary-clinicians.htm
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INFLUENZAAntiviral agents
Amantanes - target M2 ion channel protein of influenza A virus:- Amantadine and rimantadine - active against influenza A virus (not influenza B virus!)
- high levels of resistance (>99% in H3N2 and H1N1) NOT recommended for antiviral treatment or chemoprophylaxis
Neuraminidase inhibitors - active against both influenza A and B viruses:
– oral oseltamivir phosphate (Tamiflu®)
– inhaled zanamivir (Relenza®)
– intravenous peramivir (Rapivab®)
Endonuclease inhibitor (cap-dependent):- oral baloxavir marboxil (Xofluza®) - approved 2018 in Japan, USA
https://www.cdc.gov/flu/professionals/antivirals/summary-clinicians.htm
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INFLUENZAUnlicensed/unauthorised antivirals available for compassionate use
(emergency/experimental/research) in Europe, season 2017/18
European Centre for Disease Prevention and Control. Seasonal influenza vaccination andantiviral use in EU/EEA Member States – Overview of vaccine recommendations for 2017–2018 and vaccinationcoverage rates for 2015–2016 and 2016–2017 influenza seasons. Stockholm: ECDC; 2018.
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INFLUENZAThe benefit of antiviral treatment
Clinical trials and observational data:
• early antiviral treatment can shorten the duration of fever and illness symptoms
• may reduce the risk of some complications (e.g., otitis media in young children, pneumonia, and respiratory failure)
• early treatment of hospitalized adult influenza patients with oseltamivir has been reported to reduce death in some observational studies
• in hospitalized children, early antiviral treatment with oseltamivir has been reported to shorten the duration of hospitalization in observational studies.
• Clinical benefit is greatest when antiviral treatment is administered early, especially within 48 hours of influenza illness onset in clinical trials and observational studies.
https://www.cdc.gov/flu/professionals/antivirals/summary-clinicians.htm
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INFLUENZA Antiviral medications
recommended for treatment and chemoprophylaxis
https://www.cdc.gov/flu/professionals/antivirals/summary-clinicians.htm
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https://www.cdc.gov/flu/professionals/antivirals/summary-clinicians.htm
INFLUENZA Dosing of antiviral treatment and chemoprophylaxis
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INFLUENZAIndications for treatment
• hospitalized• severe, complicated, or progressive illness• at higher risk for influenza complications
• children <2 years• adults ≥65 years• people with chronic pulmonary (including asthma), cardiovascular (except
hypertension alone), renal, hepatic, hematological (including sickle cell disease), and metabolic disorders (including diabetes mellitus), or neurologic and neurodevelopment conditions (including disorders of the brain, spinal cord, peripheral nerve, and muscle, such as cerebral palsy, epilepsy [seizure disorders], stroke, intellectual disability, moderate to severe developmental delay, muscular dystrophy, or spinal cord injury)
• people with immunosuppression, including that caused by medications or by HIV infection
• women who are pregnant or postpartum (within 2 weeks after delivery)• people younger than 19 years old who are receiving long-term aspirin- or
salicylate-containing medications• people who are extremely obese• residents of nursing homes and other chronic care facilities.
https://www.cdc.gov/flu/professionals/antivirals/summary-clinicians.htm
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INFLUENZARecommendations for treatment of
suspected or laboratory confirmed influenza, season 2017/18 in Europe
European Centre for Disease Prevention and Control. Seasonal influenza vaccination andantiviral use in EU/EEA Member States – Overview of vaccine recommendations for 2017–2018 and vaccinationcoverage rates for 2015–2016 and 2016–2017 influenza seasons. Stockholm: ECDC; 2018.
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European Centre for Disease Prevention and Control. Seasonal influenza vaccination andantiviral use in EU/EEA Member States – Overview of vaccine recommendations for 2017–2018 and vaccinationcoverage rates for 2015–2016 and 2016–2017 influenza seasons. Stockholm: ECDC; 2018.
INFLUENZARecommendations for treatment
of suspected or laboratory confirmed influenza, seasons 2014/15 and 2017/18 in Europe
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INFLUENZAIndications for chemoprophylaxis
• Neuraminidase inhibitor s: 70 - 90% effective in preventing influenza
• Widespread or routine use of antiviral medications for pre-exposure or post-exposure chemoprophylaxis NOT recommended
• Indications for chemoprophylaxis for those not vaccinated and being exposed to person with influenza:
– people at high risk of influenza complications during the first two weeks following vaccination
– people at high risk for complications from influenza who cannot receive influenza vaccine due to a contraindication
– people with severe immune deficiencies or others who might not respond to influenza vaccination, such as people receiving immunosuppressive medications
• Indication to control outbreaks among high risk people in institutional settings, such as long term care facilities, is recommended.
• Antiviral chemoprophylaxis generally is not recommended if more than 48 hours have elapsed since the first exposure to a person with influenza.
https://www.cdc.gov/flu/professionals/antivirals/summary-clinicians.htm
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INFLUENZARecommendations for prophylaxis
following exposure to of suspected or laboratory confirmed influenza, season 2017/18 in Europe
European Centre for Disease Prevention and Control. Seasonal influenza vaccination andantiviral use in EU/EEA Member States – Overview of vaccine recommendations for 2017–2018 and vaccinationcoverage rates for 2015–2016 and 2016–2017 influenza seasons. Stockholm: ECDC; 2018.
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INFLUENZARecommendations for prophylaxis
following exposure to of suspected or laboratory confirmed influenza, seasons 2014/15 and 2017/18 in Europe
European Centre for Disease Prevention and Control. Seasonal influenza vaccination andantiviral use in EU/EEA Member States – Overview of vaccine recommendations for 2017–2018 and vaccinationcoverage rates for 2015–2016 and 2016–2017 influenza seasons. Stockholm: ECDC; 2018.
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Koszalka P et al. Influenza Other Respir Viruses 2017;11(3):240-246. doi: 10.1111/irv.12446.
INFLUENZA Antiviral agents currently in late-phase clinical trials
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CONCLUSIONS
• Treatment of viral infections usually symptomatic
• Systemic antiviral treatment for: HIV (31)
herpesviruses: HSV-1, HSV-2, VZV, CMV
hepatitis B virus (HBV)
hepatitis C virus (HCV)
respiratory syntitial virus (RSV)
influenza A and B virus, H1N1
• Follow the indications
• Special population for antiviral therapy: immunocompromised patients© ESCMID eLibrary by a
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Literature
• https://www.cdc.gov/mmwr/preview/mmwrhtml/rr6403a1.htm
• https://www.ncbi.nlm.nih.gov/books/NBK47401/
• http://www.idpublications.com/journals/pdfs/avres/avres_mostcited_1.pdf
• https://journals.lww.com/transplantjournal/Fulltext/2018/06000/The_Third_International_Consensus_Guidelines_on.13.aspx
• http://www.bloodjournal.org/content/131/26/2899
• https://www.uptodate.com/contents/clinical-manifestations-diagnosis-and-treatment-of-human-herpesvirus-6-infection-in-adults
• https://www.idsociety.org/globalassets/idsa/practice-guidelines/2018-seasonal-influenza.pdf
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