Antivirals Flashcards
1
Q
What is the treatment for Hep C genotype 3 with cirrhosis
A
Mavyret for 12 weeks
Vosevi for 12 weeks
If Y93H is present, add ribavirin Or consider velpatasvir/Sofosbuvir/Voxilaprevir
2
Q
What is HHV-5 and what does it cause?
A
Cytomegalovirus (CMV)
3
Q
What are the two CD4 coreceptors of HIV?
A
CXCR4 (X4)
CCR5 (R5)
4
Q
What is the backbone NRTI of all HIV therapy regimens?
A
Descovy
Truvada
Epzicom
5
Q
What is interferon for Hep C?
A
Formulations: Intron A, Infergen, Peg-intron, pegasys
MOA: induces the innate antiviral immune response
Dosing: weekly SQ injection
ADRs: FLU-LIKE SYMPTOMS, GI, photosensitivity, hepatitis flare, leucopenia, hypothyroidism, thrombocytopenia, alopecia, arthralgia
BBW: NEUROPSYCHIATRIC, autoimmune, ischemic, and infectious disorders
6
Q
What is Dolutegravir?
A
Was designed to have different mutation rates for resistance; you can still use it and just increase dose if patient develops resistance
MOA: same as RAL
Metabolism: UGT-1A1 (major) and 3A4 (minor)
ADRs: Hypersensitivity reaction, LFTs (especially in HBV or HCV coinfection), insomnia, hyperglycemia (>125 mg/dL), hypertriglyceridemia
DDIs: space 2 hours before or 6 hours after cations Mg, Al, Fe, Ca
7
Q
What is Darunavir?
A
MUST co-administer with Ritonavir
Sulfonamide so be cautious in patients with sulfa allergy
ADR: GI
Lipid neutral
8
Q
What is Havrix?
A
HAV only
Can’t give until patient is 12 months or older
2 dose series = 1st dose then 2nd dose 6-12 months later
9
Q
Which types of drugs are ineffective against oral or genital herpes?
A
topicals because of scarring associated with blisters
10
Q
What is Nevirapine?
A
Must be titrated to therapeutic dose:
200 mg once a day for 2 weeks and if there is no rash or significant change in LFTs, you can titrate to 200mg twice a day
Do NOT use in: females with CD4 > 250 cell/mm3
Males with CD4 > 400 cells/mm3
Metabolized by CYP3A4; induced CYP 3A4
ADRs: rash, liver toxicity
11
Q
How do you diagnose Hep C?
A
Check HCV antibody
RT-PCR RNA viral load
12
Q
What is the uncoating stage of viral replication?
A
Viral enzymes degrade the capsid, exposing the viral genome inside the host cell
13
Q
What is Viekira XR?
A
Paritaprevir, Ritonavir, Ombitasvir, and Dasabuvir are all in one drug but they are very large and you must take 3 once a day
MUST BE TAKEN WITH FOOD! cannot be chewed, crushed, or split
Many DDIs
ADRs: GI, rash, LFTs
14
Q
What is Tenofovir (TDF)?
A
ADRs: NEPHROTOXICITY, OSTEOMALACIA, Faconi Syndrome
OLDEST VERSION
Formulated in lactose so use caution with lactose intolerant patient
15
Q
What is HCV virus?
A
ss-RNA
Disease: Chronic Hepatitis C virus, cirrhosis, hepatocellular carcinoma
Transmission: Needles (tattoos, piercings, accupuncture), sexual, blood, vertical, razors, toothbrushes
16
Q
What is HAV virus?
A
ss-RNA
Disease: acute Hepatitis A
Transmission: Fecal-Oral, food and water, blood
17
Q
What is the most prominent and dominant mutation for Hep C genotype 1A?
A
Y93
18
Q
What are the two GI neutral protease inhibitors?
A
Atazanovir
Darunavir
19
Q
What is the treatment for Hep C genotype 3 without cirrhosis?
A
Mavyret for 8 weeks
Vosevi for 12 weeks
20
Q
What are virustatic agents?
A
antiviral agents that will slow down replication of the virus through competitive inhibition temporarily or non-competitive inhibition permanently
21
Q
What is the Hep C treatment for Genotype 1A/B if patient doesn’t have cirrhosis?
A
Zepatier for 12 weeks without NS5A RAS
Mavyret for 8 weeks
Harvoni for 12 weeks
Harvoni for 8 weeks if HCV VL <6 million
Vosevi for 12 weeks
22
Q
What is Famciclovir?
A
Prodrug of penciclovir and guanine analog
MOA: utilizes viral thymidine kinase for activation which inhibits viral DNA polymerase and prevents viral DNA synthesis
Different half lifes depending on herpes virus being treated
Use: VZV and HSV
Monitor renal function
Dosing: 2X a day
23
Q
What is Epclusa?
A
NEW gold standard in HCV management
pangenotypic for GT 1-6
ADRs: Anemia, GI, headache, fatigue, no hepatic dosing, no renal dosing
MANY DDIs with CYP 450 system
Caution in patients with CrCl < 30 mL/min
24
Q
What are viruses?
A
microscopic organism that can only replicate inside th cell of a host organism
They are completely dependent on the host
They can mutate and are subject to natural selection
25
When should you use Epzicom in HIV therapy?
When patient is HLA-B5701 negative AND baseline HIV VL <100,000 copies/mL
26
What is Twinrix?
HAV/HBV
Can't give until patient is 18 years or older
3 dose series = 1st dose, then 2nd dose at 1 month after, then 3rd dose at 6 months after
27
Which drugs block viral uncoating?
Amantadine
| Rimantadine
28
What is Stavudine?
WEIGHT DOSED
ADRs: PANCREATITIS, PERIPHERAL NEUROPATHY, lactic acidosis with hepatic steatosis, lipodystrophy
RENAL DOSING
29
What is HHV-3 and what does it cause?
Varicella Zoster Virus (VZV)
Chicken pox and shingles
30
Which drugs block viral release?
Neuraminidase inhibitors
31
Which type of influenza do we vaccinate against?
Influenza A
32
What two NRTIs are considered “kissing cousins” because they are interchangeable?
Lamivudine and Emtricitabine
33
What are the direct acting agents for Hep C?
NS5B Polymerase Inhibitors
NS3/4A protease inhibitors
NS5A inhibitor
Non-nucleoside NS5B Palm Polymerase Inhibitor
34
What is Vaqta (Merck)?
HAV Only vaccine
Can't give until patient is 12 months or older
2 dose series = 1st dose then 2nd dose 6-18 months later
35
What is the special consideration with dosing of TamiFLU?
Must be given within 48 hours of onset of the flu and taken for 5 days in order to be effective at all
36
Describe Influenza C
Infects humans, pigs, and dogs
Causes mild disease in children
37
Which drugs block late protein synthesis and processing?
Protease inhibitors
38
What are the NS3/4A mutations?
Q80K polymorphism which decreases activity of simeprevir
39
What is the dosing for Dolutegravir?
Treatment Naive = 50 mg PO once daily
Treatment experienced but INSTI naive = 50 mg PO once daily
Coadministered with EFV, fAPV/r, TPV/r, or RIF = 50 mg PO every 12 hours
INSTI-experienced with certain or suspected INSTI resistance = 50 mg every 12 hours
40
When should you start a patient on HIV therapy?
At any CD4 count and if the patient is willing to start antiretroviral therapy (ART)
41
What is HHV-1 and what does it cause?
Herpes Simplex Virus 1
Oral lesions
42
What is Mavyret?
pangenotypic for GT 1-6
Dosing: 3 tablets once a day with food
Made by the same people that made the Viekira Pak
not many DDIs
No renal dosing
ADRs: elevated total bilirubin (must monitor), HA, fatigue, GI
43
What should you always be monitoring for while patient is on HCV therapy?
SVR
44
What mutations are there for Hep C genotype 3?
M28
Q30
L31
Y93
Cause a five fold reduction in NS5A inhibitors
45
What is the MOA of Amantidine and Rimantidine?
inhibits uncoating of the viral RNA within infected host cells, thus preventing its replication
46
What is the drug of choice for the flu?
Oseltamivir (TamiFlu)
47
What is Foscarnet?
inorganic pyrophosphate analog
MOA: inhibits viral specific DNA polymerases and reverse transcriptases at the pyrophosphate binding site which prevents DNA synthesis
Excretion: 72-92% renally
IV ONLY and can accumulate in blood and cartilage and is renally toxic
Use: CMV and resistant refractory CMV and chickenpox
Monitor: Chem 10, CBC, EKG changes
48
Which NNRTI’s will the K103N mutation effect?
First generation
49
What is Zepatier?
Many DDIs; no renal or hepatic dosing required
ADRs: ELEVATED LFTs, hyperbilirubinemia; anemia, HA, fatigue, GI
50
What is Emtricitabine?
ADRs: Hyperpigmentation of palms and bottom of feet seen in clinical trials of African Americans
Fluorinated analog of lamivudine
Active against HBV
51
What is the HPV virus?
ds-DNA
Disease: Genital warts, cervical cancer
Transmission: sexual, vertical, fomites
52
What is Anti-HBc the marker for?
Hep B antibodies to core proteins
infection
53
What is Anti-HBs the marker for?
Hep B antibodies to surface antigen
Indicates recover and/or immunity (after vaccine series)
54
Which integrase inhibitor has the most DDIs?
Elvitegravir
55
What is the resistance testing in clinical practice for Epclusa regimen for Hep C?
NS5A RAS testing is recommended for GT3, treatment especially naive with cirrhosis and treat 12 weeks
If Y93H is present, add wt. based ribavirin
56
What is HBsAg the marker for?
Hep B surface antigen
Marker of infection
57
What is Daclatasvir?
Used for HCV GT3 and must be coadministered with Sofosbuvir
Metabolized by CYP3A4:
if taken with 3A4 inhibitor reduce dose to 30 mg
if taken with 3A4 inhibitor increase dose to 90 mg
Pgp efflux pump substrate and inhibitor
ADRs: anemia, fatigue, GI effects, headache
58
What is Cidofovir?
Acyclic cytidine nucleotide analog
IV ONLY
Use: systemic or severe herpes infections, HSV meningitis, CMV meningitis or gastritis
Highly renal toxic and will accumulate in the kidneys and cause problems
HYDRATE!
Can be given with probenecid to maintain plasma concentrations
59
Which Hep C GT 1A/B and 3 drugs can be used in patients with Chronic kidney disease that are on dialysis?
Elbasvir 50mg/Grazoprevir 100mg for 12 weeks
Glecaprevir 300mg/Pibrentasvir 120mg for 8-16 weeks
60
What Hep C genotype is found in the US mostly?
Genotype 1A
61
Which Hep C drugs do not require dose adjustment for patients with chronic kidney disease that are not on dialysis?
```
Daclatasvir
Elbasvir 50mg/Grazoprevir 100mg
Glecaprevir 300mg/Pibrentasvir 120mg
Ledipasvir 90mg/Sofosbuvir 400mg
Sofosbuvir 400mg/Velpatasvir 100mg
Simeprevir 150mg
Sofosbuvir 400mg/Velpatasvir 100mg/Voxilaprevir 100mg
Sofosbuvir 400mg
```
62
What should you be monitoring for prior to therapy with Hep C drugs?
```
CBC
INR
Complete LFT panel
TSH
eGFR
```
63
What is the resistance testing in clinical practice for Harvoni regimen for Hep C?
NS5A RAS testing for GT1A may be considered for treatment especially without cirrhosis
If > 100 fold resistance present, add wt. based ribavirin and treat for 12 weeks or use a different regimen
64
How do we treat hepatitis A?
with a vaccine
65
Which drugs block nucleic acid synthesis?
NRTI's
NNRTI's
Acyclovir
Foscarnet
66
What is Zanamivir?
Administration is by oral inhalation of a dry powder; needs to be coadministered with bronchodilator
Elimination: completely unchanged in urine within 24 hours
Use: prevention and treatment of Influenza A and B
Avoid use in patients with a diary allergy because milk proteins are vehicle
67
What is HAV?
Incubation period: 14-28 days
Accounts for approximately 50% of acute hepatitis in the US
Due to person to person exposure
Does not cause chronic disease
68
What is Rilpirivine?
Active against K103N virus
Dose: 25mg orally once daily and MUST BE TAKEN WITH 900 kcals of FOOD
Metabolized by CYP 3A4; substrate
ADRs: Rash, LFTs, CNS effects
DO NOT USE in patients with baseline HIV VL > 100,000 copies/mL
69
What is peginterferon alpha-2a?
MOA: inhibits viral protein production
Dosing: 180 mg SQ weekly
Hepatic Dosing and some renal dosing
Monitor: LFTs, TFTs, CBCs, triglycerides, EKG, EYE EXAM
ADRs: anemias, infections, arrhythmias, increased LFTs, hypothyroidism, psych changes, renal function
Supresses immune system and patient is at risk for increased secondary infections
70
What is the MOA of protease inhibitors?
Inhibit the activation of immature proteins by blocking the GAG-POL region within protease to inhibit the cleavage of proteins
71
What must you check for if Abacavir is part of an HIV regimen?
HLA-B5701 allele
72
What are the pyrimidine analogs?
Trifluridine
| Cidofovir
73
What counseling points should you tell your patients that currently have HCV and are on therapy?
Do NOT drink alcohol
Vaccinate against HAV and HBV
Vaccinate against pneumococcal infection in all patients with cirrhosis
Educate on how to avoid giving it to others
Educate on how to reduce liver disease
74
What are the 6 stages of viral replication?
```
Attachment
Viral Entry
Uncoating
Replication
Assembly
Release
```
75
How do you diagnose Hepatitis?
Full liver panel
Imaging - CT, MRI, and/or US
Liver biopsy
76
What is Fosamprenavir?
Sulfonamide so be cautious with sulfa allergy patients
ADRs: GI
77
What is HHV-4 and what does it cause?
Epstein Barr Virus (HBV)
Mononucleosis and lymphoma
78
How do you diagnose Hep B?
Check serology for antibodies and antigens
| RT-PCR DNA viral load
79
What is the MOA of Non-nucleoside NS5B Palm Polymerase inhibitors?
Inhibits the activity of the NS5B to inhibit HCV RNA replication
80
What is a SWITCH regimen?
Used in patient on a currently effective HIV regimen who was able to maintain viral suppression for at least 6 months and is requesting a simplification of regimen
81
What is the MOA of NRTIs?
Completely inhibits HIV-1 reverse transcriptase
82
What are virucidal agents?
antiviral agents that will kill the virus and are active only against actively replicating viruses
83
What is Ribavarin?
MOA: increase mutation frequency and inhibits HCV polymerase activity
Use: in combo with Peg-IFN therapy
Dosing: 2 divided doses = < 75kg: 1000 mg daily; >75kg: 1200 mg daily
ADRs: GI SYMPTOMS, NEUTROPENIA, headache, insomnia, fatigue, fever, pruritus, weight loss
BBW: HEMOLYTIC ANEMIA and TERATOGENICITY
84
What is HBeAg the marker for?
Hep B envelope antigen
Active viral replication
85
What are the NS5A mutations?
M28
Q30
L31
Y93
Causes five fold reduction in NS5A inhibitors
86
What genotype is now more difficult to manage thanks to treatment for 1A genotypes?
Genotype 3
87
What is the HIV virus?
2 ss-RNA
Diseases: HIV, AIDS
Route of transmission: Sexual, IVU, vertical, blood
88
What is Simeprevir?
One of the first oral agents developed and approved
ONly for GT1
Metabolized by 3A4 adn 1A2
Take with food
SULFONAMIDE ALLERGY
ADRs: Rash, LFTs, GI, and hyperbilirubinemia
89
Who do we initiate Hep C treatment in?
For all patients with chronic HCV except those with short life expectancy (<12 months) that cannot be treated with transplantation or with remediated treatment
90
What are the two categories of antiviral agents effective against herpes?
Nucleoside Analogs
| Misc. Agents
91
What are the purine analogs?
```
Acyclovir
Valacyclovir
Famciclovir
Penciclovir
Ganciclovir
Valganciclovir
```
92
What is Elvitegravir?
AKA Quad Pill
MOA: same as RAL, tenofovir, and Emtricitabine
Metabolism: 3A4 substrate; glucuronidation to a lesser extent
Dosing: must be taken daily with food
Caution in treatment naive patients and with TDF Do not use in patients with CrCl > 70 mL/min.
Elvitegravir/COBI/TDF/Emtricitabine
ADRs: New or worsening renal function, bone mineral density losses, GI
93
What is the class effect of protease inhibitors?
```
Rash
LFTs
Increase BGs causing Diabetes Mellitus
Increased triglycerides and LDL except for two
Lidodystrophy (central adipocity)
Increased CVD risks
```
Metabolized by CYP 3A4 and most are potent CYP3A4 inhibitors
HIgh genetic barrier to resistance
94
What protease inhibitor should you not use with Nelfinavir?
Ritonavir
95
What are the counseling points to prevent transmission of HCV?
Do not share toothbrushes, dental, or shaving equipment
Cover any bleeding wounds
Discuss the importance of stopping drug use and entering rehab
Do not donate blood, organs, tissue, or semen
Use condoms
Clean visibly contaminated surfaces with bleach: water at 1:9 ratio; wear gloves
96
What is Zidovudine?
ADRs: BONE MARROW SUPRESSION, myelosuppresion, macrocytic anemia, neutropenia
A high level of resistance is usually seen
97
What are interferons?
signaling proteins that are released by the host cell in response to pathogens triggering defense mechanisms within the immune system
They interfere with viral replication and activate NKCs and macrophages
98
What is the LIfe Cycle of HIV?
1. Attachment
2. Coreceptor Binding
3. Fusion
4. Uncoating
5. Reverse Transcription
6. Integration
7. Transcription
8. Translation
9. Assembly
10. Budding and Maturation
99
What is Cobistat?
Similar to Ritonavir and used as a 3A4 booster
NO HIV activity
DO NOT use with Ritonavir
ADR: Renal impairment
DO NOT use with TDF when CrCL < 70 ml/min.
100
What does IgG and IgM antibodies represent in Hep A?
```
IgG = exposure to virus, slower
IgM = acute flair, first/faster
```
101
What is Lamivudine?
WELL TOLERATED
ADRs: HEADACHE
Also active against HBV infections
Rapidly selects for mutation - M184V
102
What is Genova?
Safe in patients with CrCl > 30 mL/min. Because it has TAF
Elvitegravir/COBI/TAF/Emtricitabine
103
What is the class effect of NRTIs?
Regally dosed; except Abacavir
Mitochondrial toxicity due to inhibition of mitochondrial DNA polymerase
Lactic Acidosis and hepatic stratus is
Lipoatrophy = fat wasting in extremities, buttocks, and face (especially seen in older NRTIs)
104
What are the two Rilpivirine FDC products?
Complera
| Odefsey
105
What is Atazanavir?
ADRs: PR interval prolongation, hyperbilirubinemia
GI and Lipid neutral
106
What is the dosing for Acyclovir?
200 mg/5X a day
107
What is Anti-HBe the marker for?
Hep B antibodies to envelope antigen
Inactive viral replication; natural immunity or through treatment
108
How do you diagnose Hep A?
Check HAV IgG/IgM antibodies
| RT-PCR RNA viral load
109
What is Ganciclovir?
Guanine and Acyclovir analog
Formulations: TOPICAL OPHTHALMIC, Intravitreal implantation, oral, IV is renally toxic
Excretion: 90% in the urine unchanged
Use: CMV
Dosing: IV in large veins slowly over 1 hour
Monitor: CBCs, LFTs, renal function, serum electrolytes
110
What is Sofosbuvir?
PART OF EVERY HEP C REGIMEN = pangenotypic
MOA: uridine analog which causes HCV RNA chain terminator
Therapeutic dose is 400 mg orally
Metabolism: hydrolysis = NO CYP 450
Substrate of p-glycoprotein efflux pump and BCRP; no significant DDIs with inhibitors but there are with inducers
111
Which drugs block viral attachment and entry?
Enfuvirtide
Maraviroc
Docosanol
Palivisumab
112
What is the drug of choice for herpes treatment?
Acyclovir
113
Which two drugs are really old and not typically used anymore to treat influenza?
Amantidine
| Rimantidine
114
What is Lopinavir?
ADRs: GI
115
What is Tipranavir?
Only CYP 3 A4 inducer
Must be co-administered with Ritonavir
Sulfonamide so be cautious in patient with sulfa allergy
ADR: Intracranial hemorrhage
116
What is penciclovir?
Active metabolite of famciclovir and guanine analog
Topical ONLY
Use: Herpes labialis and facialis; oral herpes
117
HIV therapy will always contain what class of drug?
Integrase
118
What is HHV-2 and what does it cause?
Herpes Simplex Virus 2
Genital Lesions
119
What is Abacavir?
ADRs: RASH, CVD risk in MIs and strokes
Hypersensitivity reactions, occasionally fatal
Do not use: baseline HIV VL > 100,000 copies/mL
Need testing for HLA-B5701 allele before initiation is recommended to identify the patients with an increased risk of an associated hypersensitivity reaction
120
What is Entecavir?
Guanosine Analog
Dosing: 1mg/day normally or 0.5 mg/day for renal dosing; oral tablet or solution and they are NOT bioequivalent
Elimination via urine
Renal dosing when CrCl < 50 mL/min.
Monitor: LFTs and renal function, total bilirubin and BGs
TAKE ON EMPTY STOMACH
121
What is Maraviroc?
Entry Inhibitor
MOA: Inhibits HIV co-receptor CCR5-tropic-HIV-1 infection
MUST test for co-receptor tropism prior to use
Metabolized by CYP 3A4; substrate
Dose: 300 mg PO every 12 hours
With inhibitor = 150 mg every 12 hour
With inducer = 600 mg every 12 hours
ADRs: LFTs, rash, pyrexia, orthostasis
122
What is Influenza A, B, and C virus?
ss-RNA
Disease: the Flu
Transmission: Inhalation (coughing, sneezing), bird droppings
123
Describe Influenza A
Most common, most pathogenic type of influenza
Infects: humans, pigs, and horses
124
What is Enfuviritide?
Fusion Inhibitor
MOA: inhibits gp41 and prevents the fusion of HIV to CD4 cell surface
Only SQ product and requires refrigeration
ADRs: infection site reactions, GI
Dose: 90 mg every 12 hours
125
Which two protease inhibitors can be given with Cobistat?
Atazanavir
| Darunavir
126
What is MOA of NS3/4A protease inhibitors?
inhibits the cleavage of polyproteins into nonstructural proteins that are essential in HCV replication
Lower barrier to resistance
127
What does a negative Anti-HBs but positive for all other serological markers indicate?
Acute infection; highly infectious
128
What is Valacyclovir?
prodrug of acyclovir and has better bioavailability which requires less frequent dosing
Oral formulation only
129
What is Didanosine?
WEIGHT DOSED
ADRs: PANCREATITIS, PERIPHERAL NEUROPATHY, Lipoatrophy
RENAL DOSING
130
What are the three parts of a virus?
Helical Genetic Molecule
Protein Coat
Envelope
131
What is Trifluridine?
Thymidine analog
Opthalmic solution ONLY
Use: Ocular herpes
Administration: refrigerated eyedrops
132
WHta is Saquinavir?
ADRs: GI, CVD risk
133
What does positive for Anti-HBs and Anti-HBc but negative for all others indicate?
Resolved infection or immune due to natural infection
134
What is adefovir?
Adenosine Analog
Use: Hep B; effective against lamivudine-resistant HBV
Dosing: 10 mg/day oral
Renal Dosing when CrCl < 50 mL/min.
Monitor: LFTs and renal function
DO NOT USE WITH TENOFOVIR
135
What is Idinavir?
ADRs: Nephrolithiasis, Hyperbilirubinemia
136
What should you monitor during therapy with Hep C drugs?
Check HCV VL at week 4 and 12 and d/c therapy if detectable at week 6 or later
Check the same routine labs as you did prior to therapy
137
What is Telbivudine?
Thymidine analog
Dosing: 600 mg/day orally
Renal dosing when CrCl < 50 mL/min.
Monitor LFTs
Super expensive and not typically used
138
What is the MOA of NS5B Polymerase Inhibitors?
nucleoside/nucleotide analogs that incorporate into HCV RNA leading to chain termination which stops HCV replication
139
Who should get tested for Hep C?
All persons born between 1945-1965 regardless of risk factors should be tested at least once
Those with risk behaviours, exposures, and/or conditions such as: IVDU, intranasal drug users, long term HD, tattoos in unregulated setting, healthcare providers, children born to HCV mothers, recipients of transfusions or organ donations before 1992, recipients of clotting factors before 1987, incarcerated individuals, HIV, MSM, solid organ donors, or unexplained elevations in ALT
140
What does positive for only Anti-HBs indicate?
Immune due to vaccine
141
What is the resistance testing in clinical practice for Zepatier regimen for Hep C?
NS5A RAS testing for GT1A
If present, wt. based ribavirin should be added and treat for 16 weeks or use different regimen
142
What does negative Anti-HBs, +/- HBeAg, and positive for all other serological markers indicate?
chronic infection
143
What are non-nucleoside reverse transcriptase inhibitors (NNRTIs)?
Bind noncompetitively to allosteric site
Baseline genotypes resistance testing is recommended
Extremely long half life = adherence forgiving and 95% adherence rate is required in order to maintain therapeutic concentrations
Resistance occurs rapidly with mono therapy and results from single mutation = they have lowest genetic barrier to resistance
144
What is the resistance testing in clinical practice for Daclatasvir + Sofosbuvir regimen for Hep C?
NS5A RAS testing is recommended for GT3 treatment espeically without cirrhosis or naive with cirrhosis and treat for 12 weeks
If Y93H is present, add wt. based ribavirin
145
What is Valganciclovir?
prodrug of Ganciclovir
Oral tablet that MUST be taken with food for higher absorption
Renally excreted
Use: CMV
Monitor: CBCs and renal function
146
What is Rimantidine?
Use: prevents and treats Influenza A
Excretion: 70-85% in urine
Elimination: 13-65 hours
Dosing: tablets and syrup
RENAL and LFT monitoring
147
What is the MOA of NS5A inhibitors?
inhibits the phosphorylation of proteins required for HCV RNA replication which prevents HCV RNA replication
Associated with resistance mutations which decreases its activity
148
What is Oseltavmivir?
Prodrug and oral agent that is converted to oseltamivir carboxylate
Excretion: 99% in urine
Use: prevention and treatment of Influenza A and B
Renally dosed
149
What is Harvoni?
Combo drugs
Elimination via p-glycoprotein efflux pumps and BCRP
Minimal DDIs: acid suppresants, tenofovir causing nephrotoxicity, amiodarone causes symptomatic bradycardia
ADRs: Asthenia, hyperbilirubinemia, fatigue/headache, GI effects, no hepatic dosing, no renal dosing
DO NOT USE IN PATIENTS WITH CrCl < 30 mL/min.
150
What does negative for all serological markers indicate?
Not infected; not vaccinated; susceptible to Hep B
151
What is Etravine?
Active against K103N virus
Dose: 200 mg orally every 12 hr.
Metabolized by CYUP 3A4; induces and inhibits CYP 3A4
ADRs: Rash, LFTs, minor CNS effects
152
What is interferon alpha-2b
MOA: inhibits viral protein production
Use: refractory Hep B that doesn't respond to oral agents
IM injection, IV and SQ
Highly toxic
Monitor: LFTs, TFTs, CBCs, triglycerides, and EKG
ADRs: anemias, infections, arrhythmias, LFTs, hypothyroidism, psych changes (mood)
153
What is the MOA of Oseltamivir and Zanamivir?
inhibits neuraminidase of influenza a and b, preventing the release of virions from the host cell and prevents entry into the cell
154
What is Acyclovir?
Guanine analog that is ONLY effective against actively replicating virus; oldest herpes drug we have
Use: HSV, VZV, limited CMV and EBV
Formulations: oral, IV is renally toxic, and topical
Elimination: 90% renally = renal dosing
Dosing varies for stage of disease
155
What mutations exist for Hep C genotype 1a?
NS3/4A mutation
| NS5A mutations
156
What is HBV virus?
ds-DNA-RT
Disease: Chronic Hepatitis B, cirrhosis, hepatocellular carcinoma
Transmission: blood, sexual, IVU, vertical
157
What is HHV-8 and what does it cause?
Kaposi's Sarcoma typically found on bottom of feet and palms of older sicilian women
158
What must we test for with Hep C and why?
we must do resistant testing as part of therapy for Hep C because 75% of patients have resistance to GT1A and 10-15% have mutations to 5A polymerase inhibitor
159
What is Lamivudine?
Cytosine Analog and also classified as NRTI
Dosing: 100 mg if only for Hep B and 300 mg if for coinfection with HIV; oral tablet or suspension are bioequivalent to eachother
Use: coinfection with HBV and HIV 1 or 2
Renal dosing if CrCl < 50 mL/min.
Monitor: LFTs and renal function, blood glucose, CBC, HIV VL/CD4 count, HBV VL
ADRs: GI and headache
160
What is the treatment for Hep C Genotype 1A/B if patient has cirrhosis?
Same Zepatier, Harvoni (if HCV VL > 6 million), and Epclusa regimens
Not recommended treatment with Harvoni if HCV VL < 6 million
Mavyret for 12 weeks instead of 8
161
What is HHV-6/7 and what does it cause?
Roseolavirus
162
Who should be tested yearly or every six months for Hep C?
IV drug users
HIV patients
MSM
163
Which drugs block penetration of virus?
Interferon-alpha
164
Describe Influenza B
infects humans only
165
What part of the influenza virus do we use to classify the subtypes of influenza?
surface proteins: Hemagglutinin (H) and Neuraminidase (N)
166
What two NRTIs should you NEVER use together?
Didanosine and Stavudine
167
What is Amantadine?
Use: treats and prevents Influenza A; PARKINSONS
Crosses BBB and placenta
Excretion: 90% in urine
Elimination: long half life of 7-10 days in renally impaired and 11-15 hours normally
RENAL monitoring
168
What are the HSV, CMV, EBV, VZV, HHV-8 viruses?
ds-DNA
Diseases: HSV-1/-2, CMV, mononucleosis, burkitts lymphoma, chicken pox, shingles, Kaposi's sarcoma
Route of transmission: direct contact, saliva, blodd, sexual, vertical, organ, airborne (VZV)
169
What is the goal of therapy for Hep C?
to reduce all-cause mortality and liver-related health complications by achieving sustained virologic response (SVR)
Want to cure it
170
What are the new fixed dosed protease inhibitor agents?
Evotaz
| Prezcobix
171
What is Efavirenz?
Must be taken at bedtime and on an empty stomach
ADRs: CNS effects - somnolence, fatigue, psych changes; rash, LFTs
Metabolized by CYP 3A4, induces and inhibits CYP 3A4
172
What is Biktarvy?
Bictegravir/TAF/Emtricitabine
INSTI
Use: treatment Naive and as “SWITCH” regimen
Dose: 1 tablet PO once daily
Renal issues with CrCl < 30 mL/min.
Metabolism: Glucuronidation and via CYP 3A4
ADRs: GI, headache
173
What is Tenofovir Alafenamide Fumarate (TAF)?
Safer; improves kidneys and bone marrow suppression
Newer formulation and prodrug of tenofovir
Therapeutic doses depend on the product formulation
174
What is Viekira Pak?
Many DDIs and scheduling of dosing is difficult
Paritoprevir, Ritonavir, and Ombitasvir are all in one drug + Dasabuvir
Dosing is 2 of the combo pills + the 1 regular pill twice a day
MUST BE TAKEN WITH FOOD
No renal or hepatic dosing
ADRs: GI, rash, LFTs
175
What are nucleoside analogs?
synthetic analogs of purines or pyrimidines that inhibit the viral replication through:
1. Competitive inhibition of DNA polymerase
2. Incorporation and termination of viral DNA chain
3. Inactivation of viral DNA polymerase
176
WHta is Ritonavir?
Most 3A4 potent inhibitor
ADRs: GI
177
What is Vosevi?
Pangenotypic for GT 1-6
significant DDIs:
acid suppressants = separate dose by 4 hours
H2 blockers = simultaneous or staggered dose
PPIs = omeprazole may be dosed simultaneously
DO NOT USE IF eGFR < 30 mL/min
ADRs: DEPRESSION; ELEVATED LIPASE, CPK, and total bilirubin; HA, fatigue, GI, rash
178
Which two herpesvirus families can be cross transmitted and what is the clinical significance of this?
HHV-1 and HHV-2
The antibody test for this would test for both and both would be treated the same
179
What is Raltegravir?
MOA: blocks the catalytic activity of the HIV-encoded integrase, thus preventing integration of virus DNA into the host
Metabolized by glucuronidation and does not interact with the cytochrome P450 system
Eliminated via p-glycoprotein efflux pumps
Dose: 400 mg PO every 12 hours
Resistance: Virologic failure has been uncommon in vitro resistance requires only a single point mutation at codons 148 or 155
ADRs: Rash, LFTs, Increase CPK, pyrexia
