Antiviral HIV therapy

what are the different drug names for Non-HIV viral infections?

Acyclovir (Zovirax)

Ganciclovir (Cytovene, Vitrasert)

what are characteristics of Acyclovir (Zovirax)?

purine nucleoside analog (false building block for DNA)

some resistance can form

what is Acyclovir (Zovirax) used for?

Herpes simplex viruses

varicella zoster virus

what is the MOA for Acyclovir (Zovirax)?

inhibits DNA polymerase

suppresses synthesis of viral DNA

what are adverse effects of Acyclovir?

IV therapy

• phlebitis

• reversible nephrotoxicity

Oral therapy

• GI

• vertigo

topical

• stinging sensation

what are characteristics of Ganciclovir (Cytovene, Vitrasert)?

synthetic antiviral agent

iV, oral, intraocular

when do we use Ganciclovir (Cytovene, Vitrasert)?

herpes simplex virus

epstein- barr virus

CMV (cytomegalovirus) in immunocompromised host

what are adverse effects of Ganciclovir (Cytovene, Vitrasert)?

granulocytopenia

thrombocytopenia

reproductive toxicity

what is the safety alert with Ganciclovir (Cytovene, Vitrasert)?

special handling

what are characteristics of hepatitis B (HBV)?

transmitted through blood and semen

HBV vaccine

what drugs are used to treat chronic HBV?

Peginterferon alfa-2b (PEG-Intron)

Lamivudine (Epivir-HBV): nucleoside analog

Adefovir (Hepsera)

what does Peginterferon alfa-2b (PEG-Intron) do?

boosts immune system

what is part of the interferon family?

alpha

beta

gamma

what are adverse effects of interferon alfa?

flu-like symptoms

depression

what are characteristics of hepatitis C (HCV)?

transmitted through blood and semen

no symptoms

leading reason for liver transplants

what is the drug in 2001 used for HCV?

peg-interferon+ ribavirin

what is the drug in 2011 used for HCV?

peg-interferon + ribavirin + protease inhibitors

18 pills/day

what is the drug in 2013 used for HCV?

peg-interferon + ribavirin _ sofosbuvir

what is the drug in 2014 used for HCV?

Harvoni (ledipasiver/sofosbuvir)

1 pill/day

what does Harvoni (ledipasiver/sofosbuvir) target?

viral NS5A inhibitors

RNA polymerase inhibitors

what is the new drug on BB that is used for HCV?

Epclusa (sofosbuvir/velpatasvir)

98% cure rate

what are characteristics of influenza vaccines?

egg allergies

intranasal vaccines (live, attenuated viruses)

IM vaccines

what are the first generation drugs used for influenza?

Amantidine (symmetrel)

Rimantadine (Flumadine)

what are adverse effects of 1st generation drugs for influenza?

CNS

what are the 2nd generation drugs for influenza?

Oseltamivir (Tamiflu)

Zanamivir (Relenza)

Baloxavir (Xofluza)

what doe second generation drugs for influenza do?

viral neuraminidase inhibitors (inhibit viral replication)

what are characteristics of Baloxavir (Xofluza)?

first viral endonuclease inhibitor

oral

well tolerated

inhibits viral replication

what is HIV?

human immunodeficiency virus

retrovirus, reverses transcriptase (RNA—-DNA, inserts self into human cells)

what cells does HIV attack?

CD4 helper t cells (lymphocytes)

how is HIV transmitted?

blood

bodily fluids

10 steps in replication cycle

what is the drug therapy name for HIV?

Highly active anti-retroviral therapy (HAART)

what makes up the structure of HIV?

reverse transcriptase

RNA

glycoproteins

core proteins

protein shell

lipid bilayer

what are the 10 stages of replication for HIV?

1. attachment

2. fusion

3. reverse transcriptase

4. replication

5. integration

6. transcription

7. translation

8. migration and assembly

9. budding off

10. processing by HIV protease

which receptors can attach to the replication cycle for HIV?

CCR5

CXCR4

What are the different classifications of antiretroviral drugs?

HIV fusion inhibitor

CCR5 antagonist

Reverse transcriptase inhibitors (nucleoside, non-nucleoside)

integrase inhibitor

protease inhibitor

what is the name of the nucleoside reverse transcriptase inhibitor (NRTIS) for HIV?

Zidovudine (retrovir, AZT)

Abacavir (ABC)

What is the MOA for Abacavir (ABC) and Zidovudine (Retrovir)?

inhibits HIV replication by acting as a false building block

what are adverse effects of Abacavir (ABC) and Zidovudine (Retrovir)?

Lactic acidosis

hypersensitivty rxn (HLA-B 5701= if allele present, cant take this drug)

MI

fatigue/ headache

avoid w alcohol

what is the name of the non-nucleoside reverse transcriptase inhibitors (NNRTI) for HIV?

Nevirapine (Viramune)

Efavirenz (Sustiva)

what is the MOA of Nevirapine (Viramune) and Efavirenz (Sustiva)?

binds to HIV reverse transcriptase

doesn’t work on HIV reverse transcriptase (non- competitive antagonist)

what are adverse effects of Nevirapine (Viramune) and Efavirenz (Sustiva)?

Rash

Erythema multiforme (red splotches around face)

Stevens-Johnson Syndrome

Hepatotoxicity

drug interactiosn

how do you take Efavirenz (Sustiva)?

once a day on an empty stomach with high fat meals

(like this bc we can minimize muscle wasting)

which NNRTI is preferred, Nevirapine (Viramune) or Efavirenz (Sustiva)?

Efavirenz (Sustiva)

what is the name of the integrase inhibitor for HIV?

Isentress (Raltegravir)

what is the MOA of Isentress (Raltegravir)?

HIV integrase strand transfer inhibitor (INSTI), prevents insertion of HIV DNA into CD4 cells

how is Isentress (Raltegravir) adminstered?

orally

plasma levels peak after 3 hours

what are adverse effects of Isentress (Raltegravir)?

insomnia

headache

hypersensitivity rxn (rare)

pregnancy risk (avoid breastfeeding)

what drug does Isentress (Raltegravir) interact with?

Rifampin

what is the name of the protease inhibitor for HIV?

Saquinavir (Invirase, Fortovase)

Daraunavir (Prezista)

How does Darunavir (Prezista) work?

highly active against resistant strains

Indinavir

Ritonavir

Nelfinavir

Amprenavir

Lopinavir

what drugs are these?

protease inhibitors

what are adverse effects of protease inhibitors? Saquinavir (Invirase) and Darunavir (Prezista)?

hyperglycemia/diabetes

fat redistribution

hyperlipidemia

reduced bone density

hepatotoxicity

increase bleeding and serum levels

interacts w TB drugs

what is the name of the HIV fusion inhibitor?

Enfuvirtide (Fuzeon)

what are characteristics of Enfuvirtide (Fuzeon)?

2x daily SC injections

approved in march 2003

no drug interactions

what is the MOA of Enfuvirtide (Fuzeon)?

prevents HIV from fusing to CD4 cells

what are adverse effects of Enfuvirtide (Fuzeon)?

resistance

injection site rxns (pain/tenderness)

hypersensitivity rxn

what is the CCR5 antagonist drug name?

Maraviroc (Selzentry)

how does Maraviroc (Selentry) work?

it is a CCR5 co-receptor antagonist, so it prevents HIV from getting in

what is the name of the post-attachment inhibitor?

Ibalizumab (Trogarzo)

what is the MOA of Ibalizumab (Trogarzo)?

binds to CD4 cells and blocks HV from entering cells

what is Ibalizumab (Trogarzo) used for?

resistant HIV infection

what do we need to monitor with HIV patients?

viral load (plasma HIV RNA)

CD4+ T cell counts

presence of CCR5

HIV drug resistance (mutates early)

therapeutic drug monitoring

hypersensitivity (HLA-B 5701 allele)

what are the newer drugs used for HIV?

Truvada for HIV PreP

Biktarvy

Descovy

what are the different opportunistic infections associated with HIV?

Pneumocystis pneumonia

Cytomegalovirus retinitis= leading cause of blindness

TB and MAC

Cryptococcal meningitis

VZV