Antiretrovirals Flashcards
NRTIs
Abacavir-lamivudine
Tenofovir-emtricitabine
NNRTIs
Efavirenz
Protease inhibitors
Danrunavir
fusion/attachment inhibitors
Enfuviritide
Maraviroc
Fostemsavir
Integrase inhibitors
Dolutegravir
Boosting agents
Cobicistat
Ritonavir
Antivirals are
Virustatic
Nucleuc acid analogs that inhibit replication of viral DNA/RNA
Antiviral agents are ineffective against
Latent viruses
HIV treatment
3 drug regamin (ART
2 NRTIs plus a third agent (INSTI, PI, NNRTI)
A two drug regamin for treatment of naive patients
Lamivudine-dolutegravir
PrEP
Tenofovir-emtricitabine (2 NRTIs)
Reduces HIV transmission risk
Used in high-risk HIV negative patients
Probilibilty of HIV resistence is directly proportional to
The viral load in the presence of a partially suppressive drug
Consequencers of long term HIV therapy
Lipodistrophy
Drug interactions due to inhibition of CYP3A4
Immune reconstitution inflammatory syndrome
Targets of HIV therapy
Blockade of viral attachment fusion or entry (GP41/GP120 Spike complex)
Inhibition of reverse transcriptase a viral RNA to DNA (reverse transcriptase)
Inhibition of genomic integration of viral DNA (integrase)
Inhibition of Viron assembly release in maturation (protease) 
Only NRTI prodrug
tenofovir
NRTI mechanism of action
Converted to active try phosphatases by host cell kinase that inhibit HIV reverse transcriptase and cause retroviral DNA chain termination
Tenofovir, lamivudine, emtricitabine are also active against
Hepatitis B virus
NRTI resistance
Do to monotherapy so drugs must be paired
Tenofoxir-emtricitabine
Abacavir-lamivudine
NRTI adverse effects
Mitochondrial toxicity-Myelosuppression neuropathy pancreatitis lipoatrophy hepatic stenosis
Black box warning for exacerbation of hepatitis B and cough active patients who discontinue HBV treatment
Tenofovir adverse effect
Decreased bone mineral density (suppliment calcium-vitamin D)
Renal toxicity (avoid NSAIDs)
Abacavir adverse effect
Black box warning for fatal hypersensitivity
Contraindicated in HLA-B*5701 allele-positive patients
NNRTIs mechanism
Allosteric inhibition of HIV-1
Efavirenz resistance
Due to use as a single agent
Leads to mutations in binding site that reduce affinity
NNRTI pharmacokinetics
Clearned by CYP3A4
NNRTI adverse effects
Neurologic and psychiatric (Vivid dreams dizziness headache insomnia)
Rash
Hyperlipidemia
Prolonged QT interval
Protease inhibitors mechansim
Competitive inhibition of HIV protease
Prevents cleavage of gag and poor poly proteins so virus fails to mature and remains non-infective
Resistance to protease inhibitors
High barrier to resistance
Protease inhibitor metabolism
CYP3A4
Protease inhibitors are commonly admisitered with
Boosting agents:
Ritonair- a PI that inhibits CYP3A4
Cobicistat- inhibits CYP3A4, but has no anti-retroviral activity, used to boost PIs and INSTI elvitegravir
Protease inhibitor adverse effects
Gi intollerance
Hyperlipidemia
Hyperglycemia
Drug interactions:
CYP inhibitors such as azoles (require dose reduction)
CYP inducers such as rifampin (dose escalation)
enfuvirtide is a
Meptide mimic of HIV gp41 protein
enfuvirtide mechanism
Binds gp41 tp prevent HIV envelope from fusing with T cell membrane
enfuvirtide must be given
Parenternally (only when first-line agents fail)
enfuvirtide adverse effects
Injection site reactions
Elevated risk of bacterial pneumonia
Maraviroc mechanism
Blocks CCR5 co-receotir to prevent entry (only antiretroviral that targets host protein)
Maraviroc adverse rection
Black box warning for hepatotoxicity
Fostemsavir mechanism
Prodrug that binds to gp120 and prevents attachment (only when first line agents fail)
Fostemsavir side effects
Hepatotoxicity
prolionged QT interival
INSTI (dolutegravir) mechanism
Inhibits HIV integrase to prevent insetion of viral DNA (resistance uncomon)
NSTI adverse effects
Weight gain
Neural tube defects (should be used with birth control)
