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Maraviroc
- HIV entry inhibitor
- binds CCR5 on cells targeted by HIV (allosteric inhibition of gp120/CCR5) ***targets human protein
- enhances CD4 T cell count
- viral resistance arises by changes in HIV gp120
- used as salvage therapy
- cleared by CYP3A4
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enfuvirtide
- HIV entry inhibitor
- 36 aa C peptide mimic that binds N peptide sequence on HIV gp41
- blocks membrane fusion events
- peptide mimics: expensive, causes local inflammation (IM only)
- salvage therapy
- resistance arises by changes in gp41 N peptide
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abacavir (abc)
- NRTI (guanosine analog)
- resistance from: 1. inc ability of RT to preferentially exclude incorporation of analog 2. ability of RT to remove analog from elongating chain
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emtricitabine (FTC)
- NRTI (cytosine analog)
- resistance from: 1. inc ability of RT to preferentially exclude incorporation of analog 2. ability of RT to remove analog from elongating chain
- may be used in combination pills
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lamivudine (3TC)
- NRTI (cytosine analog)
- resistance from: 1. inc ability of RT to preferentially exclude incorporation of analog 2. ability of RT to remove analog from elongating chain
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tenofovir (TDF)
- NtRTI (adenosine analog)
- resistance from: 1. inc ability of RT to preferentially exclude incorporation of analog 2. ability of RT to remove analog from elongating chain
- side effect: competes with other drugs for kidney tubule secretion
- also used for rx of HBV infection (entecavir - guanosine analog NRTI also used for HBV, poorly against HIV)
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dolutegravir
- integrase inhibitor - blocks integration of viral DNA
- Inhibits viral integrase-mediated strand transfer - joining viral DNA 3' end to cellular DNA
- resistance arises through aa changes in integrase
- commonly used
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Darunavir and Ritonavir
- HIV protease inhibitors - blocks maturation of virus particle
- resistance arises from changes in protease primarily but not exclusively at the active site
- numerous side effects: lipodystrophy (central adipose tissue)
- commonly used
- darunavir - currently favored protease inhibitor
- ritonavir - also blocks cytochrome P450 3A4 and boosts activity of other protease inhibitors
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Acyclovir and Valacyclovir
- alpha herpesvirus antiviral therapy (nucleoside analog)
- effective first line drugs
- prodrug that is activated by viral nucleoside kinase (thymidine kinase)
- drug is then incorporated into elongating DNA chain terminating production of new genomes by herpes DNA pol
- use: primary and reactivated HSV in normal and immune compromised, rx of varicella zoster in immunocompromised, prophylaxis in BMT and organ transplant, HSV encephalitis (poorly)
- acyclovir has short half life and poorly absorbed orally, valacyclovir provides more sustained and higher levels in blood
- both can elevate some HIV NRTIs
- resistance: changes in nucleoside kinase gene (more common) or DNA polymerase gene
- commonly seen in long term treatment in immunosuppressed pts
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famciclovir
- alpha herpesvirus antiviral therapy (nucleoside analog)
- acyclic guanine derivative
- 3' OH allows for short chain extension but still causes chain termination
- resistance: changes in nucleoside kinase gene (more common) or DNA polymerase gene
- commonly seen in long term treatment in immunosuppressed pts
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foscarnet
- alpha herpesvirus antiviral therapy
- phosphonoformate analogue of pyrophaosphate
- binds directly to pyrophosphate binding sites of HSV DNA pol - noncompetitive inhibitor of DNA pol activity
- selective toxicity: 100x more selective for viral vs cellular pol
- can also be used to rx beta and gamma herpesviruses
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docosanol
- alpha herpesvirus antiviral therapy
- saturated fatty alcohol that is approved as topical cream
- mixed evidence of efficacy
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ganciclovir and valganciclovir
- beta and gamma herpesvirus (primarily CMV, others not generally rx'ed)
- hydroxymethylated derivative of acyclovir used IV for treating site and life-threatening CMV infections (ie. retinitis in immunocompromised pts)
- highly toxic: granulocytopenia, thrombocytopenia, may not be reversible
- CMV does not encode nucleoside kinase, but virally encoded protein kinase is responsible for phosphorylating ganciclovir
- valganciclovir is oral prodrug of ganciclovir
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fomivirsen
- beta and gamma herpesvirus (primarily CMV, others not generally rx'ed)
- antisense RNA against CMV that can be used against CMV retinitis in immunocompromised pts
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oseltamivir (Tamiflu) and zanamivir (Relenza)
- Influenza virus neuraminidase inhibitor
- blocks release of virions from surface of infected cells
- works against Influenza A and B
- usefulness?
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amantadine
- influenza uncoating inhibitor
- block acidification of virion within endosome by binding M2 protein
- only against influenza A
- most currently circulating strains are resistant
- also serves as anti-parkinson drugs
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palivizumab
- RSV antiviral (entry inhibitor)
- prophylactic monoclonal antibody = VERY expensive, low efficacy once infected
- children w/ RSV typically rx'ed with bronchodilators and antibiotics for secondary infections
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ribavirin
- best broad spectrum antiviral available
- can be used for RSV
- guanosine analog - interferes with guanosine-dependent processes
- inhibits inosine monophosphate dehydrogenase = deplete guanoside triphosphate - including 5' capping of RNA
- base pairs with cytidine or uridine to produce mutations in viral RNA
- seems to shift CD4 T cells form Th2 to Th1 phenotype (not understood why)
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interferon α-2a
- HBV antiviral
- generates antiviral state in virally infected and nearby cells
- Hep B sensitive to antiviral state
- response rate 30-40%
- pts feel terrible while on this therapy
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simeprevir
- Hepatitis C protease inhibitor
- direct acting antiviral agent (DAA)
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sofosbuvir
- Hepatitis C polymerase inhibitor
- direct acting antiviral agent (DAA)
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pegylated interferon 2b
- used for acute cases of hepatitis C
- highly effective in clearing virus
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