Antivirals for HIV

Question 1

2 main goals of Highly active anti-retroviral therapy (HAART)

Answer 1

Reduce viral load
Maintain immune function

Question 2

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

Answer 2

Immune reconstitution inflammatory syndrome (IRIS)

Question 3

Describes a sustained reduction in HIV RNA level below the limit of detection

Answer 3

Virologic suppression

Question 4

Testing in which the virus are sequenced to identify the resistance mechanism
Should be performed prior to initiating ART and after ART fails

Answer 4

Resistance testing

Question 5

Zidovudine, Emtricitabine, Lamivudine, Abacavir, and Tenofovir are examples of this class of anti-HIV drug

Answer 5

NRTIs (nucleoside reverse transcriptase inhibitors)

Question 6

MOA of NRTIs

Answer 6

Inhibit HIV reverse transcriptase
Inhibitor of viral life cycle following lethal synthesis

Question 7

Creating a toxin from a non-toxic precursor

Answer 7

Lethal synthesis

Question 8

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

Answer 8

NRTIs (Nucleoside reverse transcriptase inhibitors)

Question 9

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

Answer 9

NRTIs (Nucleoside reverse transcriptase inhibitors)

Question 10

hepatitis B flare upon discontinuation is characteristic of this anti-HIV drug

Answer 10

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)

Question 11

NRTIs also suppress this other virus, but at doses well below the doses used to suppress HIV

Answer 11

Hep B

Question 12

NRTI inhibition of these account for potentially lethal toxicity

Answer 12

Cellular and mitochondrial DNA polymerases and kinases

Question 13

Primary toxicities of NRTIs are associated with the action of this

Answer 13

Mitochondrial action

Question 14

NRTI that is the worst primary toxicity associated with mitochondrial action

Answer 14

Zidovudine

Question 15

2 primary toxicities of NRTIs associated with mitochondrial action

Answer 15

Lactic acidosis
Severe hepatomegaly with hepatic steatosis

Question 16

NRTI that inhibits stavudine’s action

Answer 16

Zidovudine

Question 17

Zidovudine inhibits the action of this drug

Answer 17

Stavudine

Question 18

NRTI that most prominently causes pancreatitis

Answer 18

Didanosine

Question 19

NRTI that contains phenylalanine, so use should be avoided in phenylketonurics

Answer 19

Didanosine

Question 20

NRTI with higher incidence of hypersensitivity (risk highest in patients with HLA-B*5701)

Answer 20

Abacavir

Question 21

Abacavir is contraindicated in patients with this

Answer 21

HLA-B*5701 genotype
Highest risk of hypersensitivity

Question 22

Major black box warning of Abacavir

Answer 22

Hypersensitivity
(more than 2 of the following: fever, rash, nausea, vomiting, diarrhea, malaise, fatigue or achiness, dyspnea, cough)

Question 23

NRTI that:
Long duration of action allows for once daily dosing
No interactions with biotransformation pathways
Causes hyperpigmentation of soles and palms

Answer 23

Emtricitabine

Question 24

2 NRTIs with Hep B exacerbation upon discontinuation of therapy

Answer 24

Emtricitabine and Tenofovir

Question 25

Emtricitabine has exacerbation of this upon discontinuation of therapy

Answer 25

Hep B

Question 26

Prodrug converted to diphosphate form that competes with deoxyadenosine triphosphate (dATP) for access to reverse transcriptase Results in chain termination

Answer 26

Tenofovir disoproxil fumarate

Question 27

NRTI with lower incidence of mitochondrial toxicity

Answer 27

Tenofovir

Question 28

Tenofovir has lower incidence of this than other NRTIs

Answer 28

Mitochondrial toxicity

Question 29

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

Answer 29

Non-nucleoside reverse transcriptase inhibitors (NNRTIs)

Question 30

Rashes ranging from mild to severe (even life-threatening) are characteristic of this class of anti-HIV drugs

Answer 30

Non-nucleoside reverse transcriptase inhibitors (NNRTIs)

Question 31

Class of anti-HIV drugs that are all biotransformed by cytochrome P450

Answer 31

Non-nucleoside reverse transcriptase inhibitors (NNRTIs) Need to check for interactions before using with any other drug

Question 32

Doravirine, Efavirenz, Etravirine, Nevirapine, and Rilpivirine are examples of this class of anti-HIV drug

Answer 32

Non-nucleoside reverse transcriptase inhibitors (NNRTIs)

Question 33

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

Answer 33

Non-nucleoside reverse transcriptase inhibitors (NNRTIs)

Question 34

NNRTI central toxicity occurs this frequently

Answer 34

In about half of all patients

Question 35

Class of anti-HIV drugs that is an inducer of CYP3A4

Answer 35

Non-nucleoside reverse transcriptase inhibitors (NNRTIs)

Question 36

Class of anti-HIV drugs that is an inhibitor of CYP2C9 and CYP2C19

Answer 36

Non-nucleoside reverse transcriptase inhibitors (NNRTIs)

Question 37

NNRTIs are inducers of this

Answer 37

CYP3A4

Question 38

NNRTIs are inhibitors of these

Answer 38

CYP2C9 and CYP2C19

Question 39

NNRTI that is contraindicated during 1st trimester pregnancy or in women planning to conceive

Answer 39

Efavirenz

Question 40

This NNRTI is contraindicated in women with pretreatment CD4>250 cells/mm and men with CD4>400 cells/mm taking NNRTIs

Answer 40

Nevirapine

Question 41

Saquinavir, Ritonavir, Atazanavir, Tipranavir, Darunavir, and Fosamprenavir are examples of this class of anti-HIV drugs

Answer 41

Protease inhibitors

Question 42

Class of anti-HIV drugs that inhibits the immunodeficiency virus aspartic protease enzyme Blocks posttranslational processing of the essential viral protein products

Answer 42

Protease inhibitors

Question 43

Protease inhibitors inhibits this

Answer 43

The immunodeficiency virus aspartic protease enzyme Blocks posttranslational processing of the essential viral protein products

Question 44

Protease inhibitors have this action on CYP3A4

Answer 44

Are both CYP3A4 substrates and inhibitors Many drug interactions at the biotransformation level

Question 45

Protease inhibitors are both substrate and inhibitors of this

Answer 45

CYP3A4

Question 46

Class of anti-HIV drugs that are both CYP3A4 substrates and inhibitors

Answer 46

Protease inhibitors

Question 47

2 common adverse effects of protease inhibitors

Answer 47

GI upset Lipid disorders (fat redistribution and accumulation, PI-induced metabolic syndrome)

Question 48

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

Answer 48

Protease inhibitors

Question 49

Common adverse effect of protease inhibitors that involves hyperglycemia, elevated cholesterol, LDL and triglycerides, and reduced HDL

Answer 49

PI-induced metabolism syndrome

Question 50

3 severe adverse effects of protease inhibitors

Answer 50

Hyperglycemia/diabetes/pancreatitis Kidney stones Stevens-Johnson syndrome (immune disorder)

Question 51

Hyperglycemia/diabetes/pancreatitis, Kidney stones and Stevens-Johnson syndrome (immune disorder) are severe adverse effects of this class of anti-HIV drug

Answer 51

Protease inhibitors

Question 52

Protease inhibitor not well-tolerated at high doses; low doses used to "boost" other PIs

Answer 52

Ritonavir

Question 53

Most potent CYP3A4 inhibitor of protease inhibitors

Answer 53

Ritonavir

Question 54

Ritonavir inhibits these

Answer 54

Most potent CYP3A4 inhibitor of protease inhibitors Also inhibits CYP2D6 and other CYP isoforms

Question 55

Ritonavir is this class of anti-HIV drug

Answer 55

Protease inhibitor

Question 56

Intracranial hemorrhage is most common with this anti-HIV drug combination

Answer 56

Ritonavir - tipranavir combination

Question 57

2 black box warnings of Tipranavir

Answer 57

Hepatotoxicity Intracranial hemorrhage (most common with ritonavir-tipranavir combination)

Question 58

This adverse effect is most common with ritonavir - tipranavir combination

Answer 58

Intracranial hemorrhage

Question 59

Hepatotoxicity and intracranial hemorrhage are black box warnings of this

Answer 59

Tipranavir (PI)

Question 60

Enfuvirtide is in this class of anti-HIV drugs

Answer 60

Fusion inhibitor

Question 61

MOA of Enfuvirtide (fusion inhibitor)

Answer 61

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

Question 62

Enfuvirtide (a fusion inhibitor) prevents the virally induced conformational change in this which permits viral-host cell membrane fusion

Answer 62

Transmembrane glycoprotein subunit (GP41)

Question 63

Hypersensitivity (eosinophils) in up to 10% of patients occurs in this fusion inhibitor

Answer 63

Enfuvirtide (Fuseon)

Question 64

2 adverse effects of Enfuvirtide (fusion inhibitor)

Answer 64

Injection site reactions Hypersensitivity (eosinophils) in up to 10% of patients

Question 65

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)

Answer 65

Maraviroc (CCR5 antagonist)

Question 66

Maraviroc MOA

Answer 66

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)

Question 67

Maraviroc is only effective with HIV strains that are CCR5-tropic, but some strains utilize this instead

Answer 67

CXCR4

Question 68

Black box warning of Maraviroc (CCR5 antagonist)

Answer 68

Hepatotoxicity

Question 69

3 adverse effects of Maraviroc (CCR5 antagonist)

Answer 69

Hypersensitivity Cardiovascular events (MIs, hypotension) Hepatotoxicity

Question 70

Drug interaction that increases risk of serious cardiovascular events in Maraviroc (CCR5 antagonist)

Answer 70

Thioridazine (antipsychotic)

Question 71

Dolutegravir, Elvitegravir, Cabotegravir, Raltegravir and Bictegravir are examples of this class of anti-HIV drug

Answer 71

Integrase inhibitors

Question 72

3 adverse effects of integrase inhibitors

Answer 72

Rhabdomyolysis Depression with suicidal ideation Neural tube defects when used prior to conception (RAL)

Question 73

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

Answer 73

Integrase inhibitors

Question 74

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

Answer 74

Ibalizumab

Question 75

MOA of ibalizumab

Answer 75

Binds to the CD4 receptors on T cells to prevent attached HIV-1 particles from entering the cell

Question 76

Adverse effect of ibalizumab (CD4 post-attachment inhibitor)

Answer 76

Opportunistic infection susceptibility

Question 77

What is the recommended HIV treatment for naive adults (who have not tried any therapy yet)?

Answer 77

Two nucleoside/nucleotide reverse transcriptase inhibits AND: Protease inhibitor (boosted), or Non Nucleoside reverse transcriptase inhibitor, or Integrase inhibitor

Question 78

2 reasons why monotherapy with NRTI and dual NRTI regimens should be avoided

Answer 78

Rapid resistance development Inferior antiretroviral activity

Question 79

This treatment regimen has a high rate of nonresponse in treatment of naive patients

Answer 79

Triple NRTI regimens

Question 80

Only exception when triple NRTI regimens can be used

Answer 80

Patients for whom other options are worse

Question 81

Integrase inhibitor that is approved as PrEP

Answer 81

Cabotegravir (Apretude)

Question 82

Cabotegravir (Apretude) is this class of anti-HIV drug

Answer 82

Integrase inhibitor

Question 83

2 drugs that are combinations of Emtricitabine and Tenofovir

Answer 83

Truvada and Descovy

Question 84

Truvada and Descovy are combinations of these 2 drugs

Answer 84

Emtricitabine and Tenofovir

Question 85

Truvada and Descovy are used as this

Answer 85

Pre-exposure prophylaxis (PrEP)

Question 86

Truvada and Descovy are used in combination with an integrase inhibitor for this

Answer 86

Post-exposure prophylaxis (PEP)

Question 87

Truvada and Descovy are used in combination with this as post-exposure prophylaxis (PEP)

Answer 87

Integrase inhibitor

Question 88

Pharmacological enhancer of HIV drugs No action alone, but enhances HIV suppression used with protease inhibitors

Answer 88

Cobicistat (Tybost)