Antivirals for HIV Flashcards
2 main goals of Highly active anti-retroviral therapy (HAART)
Reduce viral load
Maintain immune function
Common adverse effect in the first year of ART where the patient’s recovering immune system responds to a previously acquired opportunistic infection with inflammatory response
Immune reconstitution inflammatory syndrome (IRIS)
Describes a sustained reduction in HIV RNA level below the limit of detection
Virologic suppression
Testing in which the virus are sequenced to identify the resistance mechanism
Should be performed prior to initiating ART and after ART fails
Resistance testing
7 classes of anti-HIV drugs
NRTIs
NNRTIs
Protease inhibitors
Fusion inhibitors
Integrase inhibitors
CCR5 antagonists
CD4 post-attachment inhibitor
Zidovudine, Emtricitabine, Lamivudine, Abacavir, and Tenofovir are examples of this class of anti-HIV drug
NRTIs (nucleoside reverse transcriptase inhibitors)
MOA of NRTIs
Inhibit HIV reverse transcriptase
Inhibitor of viral life cycle following lethal synthesis
Creating a toxin from a non-toxic precursor
Lethal synthesis
Class of anti-HIV drugs:
Converted to active triphosphate form that competes for nucleoside triphosphates for access to reverse transcriptase
Missing essential 3’-hydroxyl group prevents additional nucleoside addition to DNA chain
Blocks viral replication and infection of new cells
NRTIs (Nucleoside reverse transcriptase inhibitors)
These general adverse reactions are of which class of anti-HIV drug?
Fat deposit accumulation
Myopathy
Peripheral neuropathy
Anemia
Pancreatitis
Hep B flare upon discontinuation
NRTIs (Nucleoside reverse transcriptase inhibitors)
hepatitis B flare upon discontinuation is characteristic of this anti-HIV drug
NRTIs (Nucleoside reverse transcriptase inhibitors)
These reverse transcriptase inhibitors also suppress hep B virus but at doses well below the doses used to suppress HIV (Emtricitabine, Lamivudine, and Tenofovir)
NRTIs also suppress this other virus, but at doses well below the doses used to suppress HIV
Hep B
NRTI inhibition of these account for potentially lethal toxicity
Cellular and mitochondrial DNA polymerases and kinases
Primary toxicities of NRTIs are associated with the action of this
Mitochondrial action
NRTI that is the worst primary toxicity associated with mitochondrial action
Zidovudine
2 primary toxicities of NRTIs associated with mitochondrial action
Lactic acidosis
Severe hepatomegaly with hepatic steatosis
Anti-viral HIV drug whose risk of resistance may increase with interrupted therapy
There should be NO drug holidays (not currently recommended for any HIV therapy)
NRTIs
NRTI that inhibits stavudine’s action
Zidovudine
Zidovudine inhibits the action of this drug
Stavudine
4 black box warnings of Zidovudine
Myopathy with long-term use
Lactic acidosis
Hepatomegaly with hepatic steatosis
Fat redistribution and accumulation
Stavudine black box (2)
Lactic acidosis and severe hepatomegaly
Pancreatitis
NRTI that most prominently causes pancreatitis
Didanosine
NRTI that contains phenylalanine, so use should be avoided in phenylketonurics
Didanosine
2 black box warnings of Lamivudine
Lactic acidosis with severe hepatomegaly
Non-interchangeable forms (form used for Hep B is not appropriate for HIV)
NRTI with higher incidence of hypersensitivity (risk highest in patients with HLA-B*5701)
Abacavir
Abacavir is contraindicated in patients with this
HLA-B*5701 genotype
Highest risk of hypersensitivity
Major black box warning of Abacavir
Hypersensitivity
(more than 2 of the following: fever, rash, nausea, vomiting, diarrhea, malaise, fatigue or achiness, dyspnea, cough)
NRTI that:
Long duration of action allows for once daily dosing
No interactions with biotransformation pathways
Causes hyperpigmentation of soles and palms
Emtricitabine
2 black box warnings of Emtricitabine
Lactic acidosis and severe hepatomegaly
Hep B exacerbation upon discontinuation of therapy
2 NRTIs with Hep B exacerbation upon discontinuation of therapy
Emtricitabine and Tenofovir
Emtricitabine has exacerbation of this upon discontinuation of therapy
Hep B
Prodrug converted to diphosphate form that competes with deoxyadenosine triphosphate (dATP) for access to reverse transcriptase
Results in chain termination
Tenofovir disoproxil fumarate
NRTI with lower incidence of mitochondrial toxicity
Tenofovir
Tenofovir has lower incidence of this than other NRTIs
Mitochondrial toxicity
Class of anti-HIV drugs that Inhibit reverse transcriptase by binding near the active site and inducing a conformational change that blocks enzyme activation (also known as: allosteric antagonists)
No activation required
All cause rash, sometimes severe
All biotransformed by cytochrome P450
Non-nucleoside reverse transcriptase inhibitors (NNRTIs)
Rashes ranging from mild to severe (even life-threatening) are characteristic of this class of anti-HIV drugs
Non-nucleoside reverse transcriptase inhibitors (NNRTIs)
Class of anti-HIV drugs that are all biotransformed by cytochrome P450
Non-nucleoside reverse transcriptase inhibitors (NNRTIs)
Need to check for interactions before using with any other drug
Doravirine, Efavirenz, Etravirine, Nevirapine, and Rilpivirine are examples of this class of anti-HIV drug
Non-nucleoside reverse transcriptase inhibitors (NNRTIs)
Class of anti-HIV drug where central toxicity occurs in about half of all patients
Dizziness, headache, insomnia, euphoria, impaired cognition, nightmares, hallucinations
Most common in first weeks or months of therapy and fade with continued use
Old FDA pregnancy category D
Non-nucleoside reverse transcriptase inhibitors (NNRTIs)
NNRTI central toxicity occurs this frequently
In about half of all patients
Class of anti-HIV drugs that is an inducer of CYP3A4
Non-nucleoside reverse transcriptase inhibitors (NNRTIs)
Class of anti-HIV drugs that is an inhibitor of CYP2C9 and CYP2C19
Non-nucleoside reverse transcriptase inhibitors (NNRTIs)
NNRTIs are inducers of this
CYP3A4
NNRTIs are inhibitors of these
CYP2C9 and CYP2C19
NNRTI that is contraindicated during 1st trimester pregnancy or in women planning to conceive
Efavirenz
This NNRTI is contraindicated in women with pretreatment CD4>250 cells/mm and men with CD4>400 cells/mm taking NNRTIs
Nevirapine
2 contraindications of NNRTIs
Efavirenz
Nevirapine
Saquinavir, Ritonavir, Atazanavir, Tipranavir, Darunavir, and Fosamprenavir are examples of this class of anti-HIV drugs
Protease inhibitors
Class of anti-HIV drugs that inhibits the immunodeficiency virus aspartic protease enzyme
Blocks posttranslational processing of the essential viral protein products
Protease inhibitors
Protease inhibitors inhibits this
The immunodeficiency virus aspartic protease enzyme
Blocks posttranslational processing of the essential viral protein products
Protease inhibitors have this action on CYP3A4
Are both CYP3A4 substrates and inhibitors
Many drug interactions at the biotransformation level
Protease inhibitors are both substrate and inhibitors of this
CYP3A4
Class of anti-HIV drugs that are both CYP3A4 substrates and inhibitors
Protease inhibitors
2 common adverse effects of protease inhibitors
GI upset
Lipid disorders (fat redistribution and accumulation, PI-induced metabolic syndrome)
Lipid disorders; fat redistribution and accumulation, PI-induced metabolic syndrome (hyperglycemia, elevated cholesterol, LDL and triglycerides, reduced HDL)
These are common adverse effects of this class of anti-HIV drug
Protease inhibitors
Common adverse effect of protease inhibitors that involves hyperglycemia, elevated cholesterol, LDL and triglycerides, and reduced HDL
PI-induced metabolism syndrome
3 severe adverse effects of protease inhibitors
Hyperglycemia/diabetes/pancreatitis
Kidney stones
Stevens-Johnson syndrome (immune disorder)
Hyperglycemia/diabetes/pancreatitis, Kidney stones and Stevens-Johnson syndrome (immune disorder) are severe adverse effects of this class of anti-HIV drug
Protease inhibitors
Protease inhibitor not well-tolerated at high doses; low doses used to “boost” other PIs
Ritonavir
Most potent CYP3A4 inhibitor of protease inhibitors
Ritonavir
Ritonavir inhibits these
Most potent CYP3A4 inhibitor of protease inhibitors
Also inhibits CYP2D6 and other CYP isoforms
Ritonavir is this class of anti-HIV drug
Protease inhibitor
Intracranial hemorrhage is most common with this anti-HIV drug combination
Ritonavir - tipranavir combination
2 black box warnings of Tipranavir
Hepatotoxicity
Intracranial hemorrhage (most common with ritonavir-tipranavir combination)
This adverse effect is most common with ritonavir - tipranavir combination
Intracranial hemorrhage
Hepatotoxicity and intracranial hemorrhage are black box warnings of this
Tipranavir (PI)
Enfuvirtide is in this class of anti-HIV drugs
Fusion inhibitor
MOA of Enfuvirtide (fusion inhibitor)
Prevents the virally induced conformational change in transmembrane glycoprotein subunit (GP41) permitting viral-host cell membrane fusion
Unique mechanism may add effectiveness to existing HIV therapies
Enfuvirtide (a fusion inhibitor) prevents the virally induced conformational change in this which permits viral-host cell membrane fusion
Transmembrane glycoprotein subunit (GP41)
Hypersensitivity (eosinophils) in up to 10% of patients occurs in this fusion inhibitor
Enfuvirtide (Fuseon)
2 adverse effects of Enfuvirtide (fusion inhibitor)
Injection site reactions
Hypersensitivity (eosinophils) in up to 10% of patients
Anti-HIV drug that interferes with entry of HIV into host cells by inhibiting fusion with outer membrane
Only effective with HIV strains that are CCR5-tropic (some virus strains utilize CXCR4)
Maraviroc (CCR5 antagonist)
Maraviroc MOA
Interferes with entry of HIV into host cells by inhibiting fusion with outer membrane
Only effective with HIV strains that are CCR5-tropic (some virus strains utilize CXCR4)
Maraviroc is only effective with HIV strains that are CCR5-tropic, but some strains utilize this instead
CXCR4
Black box warning of Maraviroc (CCR5 antagonist)
Hepatotoxicity
3 adverse effects of Maraviroc (CCR5 antagonist)
Hypersensitivity
Cardiovascular events (MIs, hypotension)
Hepatotoxicity
Drug interaction that increases risk of serious cardiovascular events in Maraviroc (CCR5 antagonist)
Thioridazine (antipsychotic)
Dolutegravir, Elvitegravir, Cabotegravir, Raltegravir and Bictegravir are examples of this class of anti-HIV drug
Integrase inhibitors
3 adverse effects of integrase inhibitors
Rhabdomyolysis
Depression with suicidal ideation
Neural tube defects when used prior to conception (RAL)
Rhabdomyolysis, Depression with suicidal ideation, and Neural tube defects when used prior to conception (RAL) are adverse effects of this class of anti-HIV drug
Integrase inhibitors
Humanized monoclonal antibody indicated for treatment-resistant HIV1 in experienced patients
binds to the CD4 receptors on T cells to prevent attached HIV-1 particles from entering the cell
Ibalizumab
MOA of ibalizumab
Binds to the CD4 receptors on T cells to prevent attached HIV-1 particles from entering the cell
Adverse effect of ibalizumab (CD4 post-attachment inhibitor)
Opportunistic infection susceptibility
What is the recommended HIV treatment for naive adults (who have not tried any therapy yet)?
Two nucleoside/nucleotide reverse transcriptase inhibits AND:
Protease inhibitor (boosted), or
Non Nucleoside reverse transcriptase inhibitor, or
Integrase inhibitor
2 reasons why monotherapy with NRTI and dual NRTI regimens should be avoided
Rapid resistance development
Inferior antiretroviral activity
This treatment regimen has a high rate of nonresponse in treatment of naive patients
Triple NRTI regimens
Only exception when triple NRTI regimens can be used
Patients for whom other options are worse
Integrase inhibitor that is approved as PrEP
Cabotegravir (Apretude)
Cabotegravir (Apretude) is this class of anti-HIV drug
Integrase inhibitor
2 drugs that are combinations of Emtricitabine and Tenofovir
Truvada and Descovy
Truvada and Descovy are combinations of these 2 drugs
Emtricitabine and Tenofovir
Truvada and Descovy are used as this
Pre-exposure prophylaxis (PrEP)
Truvada and Descovy are used in combination with an integrase inhibitor for this
Post-exposure prophylaxis (PEP)
Truvada and Descovy are used in combination with this as post-exposure prophylaxis (PEP)
Integrase inhibitor
Pharmacological enhancer of HIV drugs
No action alone, but enhances HIV suppression used with protease inhibitors
Cobicistat (Tybost)
