Antiviral therapy
Practical Points
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No treatment for most viral disease
Prevention is the mainstay
Vaccinations
 Social distancing
 Hand hygiene
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Antibiotic stewardship
Overview
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Identify the few situations where viral infections
are treatable
Understand BASIC mechanism of action (when
known) of appropriate antiviral, window when
intervention is meaningful, resistance patterns
and toxicity of treatment
N.B. Viral hepatitis will be discussed later this week and will not be covered
Case 1
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35 year old male with 4 days of rhinorrhea, nasal
congestion and pharyngitis; he mentions this
incidentally during his routine follow up for
HLP.
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4 children at home, 2 of them are under 5 and in day
care
Case 1
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What is the likely pathogen?
What is the only intervention shown to have
efficacy in this situation? (despite numerous
trials)
When is the therapeutic window?
When do we start worrying this might not be a
virus and feel inclined to treat (i.e. acute bacterial
sinusitis)?
Rhinovirus

What is the only intervention shown to have
efficacy in this situation? (despite numerous
trials)

Zinc (nasal gel better than lozenge)
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Inhibits RNA polymerase
– not echinacea, Vit C
When is the therapeutic window?

First 24 hrs, and only decreases time to resolution by
1-2 days
Case 2
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You are on your geriatric rotation in February
and while on rounds the charge nurse informs
you of 6 residents with myalgias, respiratory
illness and fever, 2 of whom were hospitalized
yesterday

The remaining 4 have become symptomatic over the last
day
Case 2
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What is the viral likely pathogen?
What is the significance of the month and setting of
infection?
What is your intervention?
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What info would be helpful in making your decision?
What aspects of drug toxicity and tx spectrum are
important to consider?
What could have prevented this outbreak? (possibly) –
think broadly (i.e. introduction and propagation)
Influenza

What is the significance of the month and setting of
infection?
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Waning immunity in nursing home residents from initial
vaccination (and overall poor response)
What is your intervention?

Neuraminidase inhib +/- rimantidine*
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(w/i 48 hrs sx)
What info would be helpful in making your decision?
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
Current influenza activity in the community
http://www.cdc.gov/flu/weekly
*http://www2a.cdc.gov/HAN/ArchiveSys/ViewMsgV.asp?AlertNum=00279
Influenza

What aspects of drug toxicity and tx spectrum
are important to consider?
Oseltamavir – NA/particle cleavage and release; GI
sx
 Zanamavir – NA/particle cleavage and release;
asthma exacerbation, requires cooperative patient
 Rimantidine – ? Viral Uncoating; (only good for flu
A)
 Ribavirin – guanosine analogue; not FDA approved
for flu, off-label for combo with oselt

Influenza

What could have prevented this outbreak?
(possibly) – think broadly (i.e. introduction and
propagation)
Revaccination of residents (?) – probably not
 Compliance with vaccination of HCPs (usu <50%) YES

50K die and 350K are hospitalized each year from SEASONAL influenza in the US
Avian Influenza – 1997 and forward
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Total # of human deaths = 254 (63% case fatality)
# countries = 15, leading: Indonesia, Viet Nam
Animal control (vaccination and culling) controls the
infection

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Use of PPE, avoidance of bird markets, thorough
cooking of potentially infected meat
Neuraminidase inhibitors work, theoretically

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Government compensation is key
Increasing resistance
Human vaccine in the works
http://www.who.int/csr/disease/avian_influenza/country/cases_table_2009_02_09/en/index.html
Case 3
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22 yo active duty male presents to sick call with
this eruption
Case 3
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What two viruses is he infected with? (at a
minimum)
Describe the treatment options for both

What additional information would be helpful in
making a decision
Clinical
 laboratory
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HIV
Antiretroviral treatment is:
Complex (and evolving)*
 Requires extreme dedication
 Selection guided by genotype/phenotype
 Ideally at least 3 active agents
 Response should be monitored
 Toxicity monitored and offset (?more meds)


No vaccine in the foreseeable future
*http://www.aidsinfo.nih.gov/Guidelines/GuidelineDetail.aspx?GuidelineID=7
HIV
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Monitor toxicity
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Allergy / hypersensitivity
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Genetic screening for abacavir
Long term effects
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Protease inhibitors (PIs) – lipids, glucose
Non-nucleoside reverse transcriptase inhibitors (NNRTIs) – lipids
(TG), hepatic
nucleoside reverse transcriptase inhibitors (NRTIs) – renal, marrow,
neuropathy
Integrase inhibitors – myositis
CCR5 receptor blocker - hepatitis
Herpesviridae

Acyclovir and its derivatives

fam, val
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Increased bioavailability (and cost), same spectrum
Inhibits viral DNA polymerase
 Thymidine kinase mutants  resistance
 HSV>VZV>>EBV≠CMV (intrinsically resistant)
 Iv form --? Crystalluria/stones
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Herpesviridae
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Foscarnet or ganciclovir:
CMV and acyclovir resistant HSV
 Toxicity:

foscarnet: renal tox, sz,
 gancyclovir: marrow suppression
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Case 4
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30 yo unmarried active duty male presents with
the following lesions which have developed over
several months

He reports unprotected sex with 3 partners over the
last year
Case 4
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What virus is responsible for these lesions?
What cancers has it been associated with?
What methods of treatment exist?
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Major side effects from each?
What further work up should ensue?
What surgical intervention would decrease STD
transmission to his female partners and decrease
his risk of cancer?
HPV
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What cancers has it been associated with?
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Cervical
Penile
Anal
What methods of treatment exist?
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Physical destruction / removal
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Cryo, laser, surgery (pain, scarring)
Local Immune enhancement
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Imiquimod (irritation)
HPV
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What further work up should ensue?
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Full STD evaluation – HIV, RPR, gc/chlam, Hep B,
Hep C
What surgical intervention would decrease STD
transmission and cancer risk to the patient and
partners?

circumcision
http://www.who.int/hiv/topics/malecircumcision/en/index.html
http://www.cdc.gov/hiv/resources/factsheets/circumcision.htm
Case 5
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28 yo female presents to her primary care doctor
after developing a painful and itchy blisters on
her face 1 week after seeing her boyfriend who
has since deployed to Iraq
Case 5
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What pre-deployment vaccination is the source
for this infection?
What drugs/biologics are available for
intervention?
What are indications for treatment?
What are the potential side effects?
Poxviridae
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Orthopoxviruses (Monkeypox, vaccinia) –
potentially life threatening
VIG-IV (allergic reaxn-rigors, fever)
 Cidofovir: targets DNA polymerase
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nephrotoxic – needs to be given with hydration and
probenecid
ST-246: targets viral maturation
ORAL
 placebo-like
 Works against CDF-resistant strains
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http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5204a1.htm
Poxviridae
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Parapoxviruses and molluscum contagiosum –
localized, only serious in immunocompromised
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Imiquimod, intralesional cidofovir
Orf virus infection
Case 6
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8 year old Filipina girl BIB parents 2 weeks after
sustaining a bite to the face from a local dog.
She is currently exhibiting tremors, slurred
speech and she is refusing to eat/drink
Case 6
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What virus is responsible for her condition?
What interventions are recommended in the
acute setting of such a dog bite (asymptomatic
patients)?
What recent protocol has saved the lives of at
least 2 symptomatic patients?
What is the risk to close contacts/health care
providers of this girl?
Rabies
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What interventions are recommended in the
acute setting of such a dog bite (asymptomatic
patients)?
RIG (not needed if pre-exposure vax given)
 Rabies vaccine
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What recent protocol has saved the lives of at
least 2 symptomatic patients?
Rabies
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Milwaukee protocol
Ketamine, midazolam, ribavirin, amantadine
 No vaccine/biologic (fear of potentiating immune
response)
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Potential risk to HCPs
Never been documented
 At least 2 non-lab confirmed human-to-human via
saliva
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Rabies in a dog imported from Iraq--New Jersey, June 2008.
Centers for Disease Control and Prevention (CDC).
MMWR Morb Mortal Wkly Rep. 2008 Oct 3;57(39):1076-8. No abstract available.
Case 7
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30 yo female missionary returns from Nigeria
with facial/neck edema, fever, conjunctivitis and
one bout of bloody emesis. She reports living in
a rural village for 1 month and did indulge in the
local delicacy of grilled rodent which she helped
her host family to prepare.
Case 7
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What is the likely viral etiology?
What is the reservoir?
Are healthcare workers at risk for infection?
What drug may be of benefit?
Lassa Fever
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What is the reservoir?
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Are healthcare workers at risk for infection?
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mastomys
Yes, contact precautions
What drug may be of benefit?
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Ribavirin
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Hemolytic anemia, teratogen
Activity against arenaviridae (LF) and bunyaviridae (CCHF)
References
Survival after treatment of rabies with induction
of coma. Willoughby RE et al.
N Engl J Med. 2005 Jun 16;352(24):2508-14.
 Combinatorial ribavirin and interferon alfacon-1
therapy of acute arenaviral disease in hamsters.
Gowen BB et al. Antivir Chem Chemother.
2006;17(4):175-83.
http://www.cdc.gov/ncidod/dvrd/spb/mnpages
/dispages/lassaf.htm
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References cont.
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Efficacy of zinc against common cold viruses: an
overview. J Am Pharm Assoc (2003). 2004 SepOct;44(5):594-603
Clinical practice. Prevention and treatment of seasonal
influenza. N Engl J Med. 2008 Dec 11;359(24):2579-85
Successful Treatment in the Monkeypox and
Variola Primate Models of Smallpox by the Oral
Drug ST-246 Antiviral Research
Volume 74, Issue 3, June 2007, Page A35
References cont.
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http://www.cdc.gov/mmwr/preview/mmwrht
ml/rr57e507a1.htm (human rabies prevention,
2008 recommendations)