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

7 classes of anti-HIV drugs

Answer 5

NRTIs
NNRTIs
Protease inhibitors
Fusion inhibitors
Integrase inhibitors
CCR5 antagonists
CD4 post-attachment inhibitor

Question 6

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

Answer 6

NRTIs (nucleoside reverse transcriptase inhibitors)

Question 7

MOA of NRTIs

Answer 7

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

Question 8

Creating a toxin from a non-toxic precursor

Answer 8

Lethal synthesis

Question 9

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 9

NRTIs (Nucleoside reverse transcriptase inhibitors)

Question 10

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 10

NRTIs (Nucleoside reverse transcriptase inhibitors)

Question 11

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

Answer 11

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 12

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

Answer 12

Hep B

Question 13

NRTI inhibition of these account for potentially lethal toxicity

Answer 13

Cellular and mitochondrial DNA polymerases and kinases

Question 14

Primary toxicities of NRTIs are associated with the action of this

Answer 14

Mitochondrial action

Question 15

NRTI that is the worst primary toxicity associated with mitochondrial action

Answer 15

Zidovudine

Question 16

2 primary toxicities of NRTIs associated with mitochondrial action

Answer 16

Lactic acidosis
Severe hepatomegaly with hepatic steatosis

Question 17

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)

Answer 17

NRTIs

Question 18

NRTI that inhibits stavudine’s action

Answer 18

Zidovudine

Question 19

Zidovudine inhibits the action of this drug

Answer 19

Stavudine

Question 20

4 black box warnings of Zidovudine

Answer 20

Myopathy with long-term use
Lactic acidosis
Hepatomegaly with hepatic steatosis
Fat redistribution and accumulation

Question 21

Stavudine black box (2)

Answer 21

Lactic acidosis and severe hepatomegaly
Pancreatitis

Question 22

NRTI that most prominently causes pancreatitis

Answer 22

Didanosine

Question 23

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

Answer 23

Didanosine

Question 24

2 black box warnings of Lamivudine

Answer 24

Lactic acidosis with severe hepatomegaly
Non-interchangeable forms (form used for Hep B is not appropriate for HIV)

Question 25

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

Answer 25

Abacavir

Question 26

Abacavir is contraindicated in patients with this

Answer 26

HLA-B*5701 genotype Highest risk of hypersensitivity

Question 27

Major black box warning of Abacavir

Answer 27

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

Question 28

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

Answer 28

Emtricitabine

Question 29

2 black box warnings of Emtricitabine

Answer 29

Lactic acidosis and severe hepatomegaly Hep B exacerbation upon discontinuation of therapy

Question 30

2 NRTIs with Hep B exacerbation upon discontinuation of therapy

Answer 30

Emtricitabine and Tenofovir

Question 31

Emtricitabine has exacerbation of this upon discontinuation of therapy

Answer 31

Hep B

Question 32

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

Answer 32

Tenofovir disoproxil fumarate

Question 33

NRTI with lower incidence of mitochondrial toxicity

Answer 33

Tenofovir

Question 34

Tenofovir has lower incidence of this than other NRTIs

Answer 34

Mitochondrial toxicity

Question 35

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 35

Non-nucleoside reverse transcriptase inhibitors (NNRTIs)

Question 36

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

Answer 36

Non-nucleoside reverse transcriptase inhibitors (NNRTIs)

Question 37

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

Answer 37

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

Question 38

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

Answer 38

Non-nucleoside reverse transcriptase inhibitors (NNRTIs)

Question 39

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 39

Non-nucleoside reverse transcriptase inhibitors (NNRTIs)

Question 40

NNRTI central toxicity occurs this frequently

Answer 40

In about half of all patients

Question 41

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

Answer 41

Non-nucleoside reverse transcriptase inhibitors (NNRTIs)

Question 42

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

Answer 42

Non-nucleoside reverse transcriptase inhibitors (NNRTIs)

Question 43

NNRTIs are inducers of this

Answer 43

CYP3A4

Question 44

NNRTIs are inhibitors of these

Answer 44

CYP2C9 and CYP2C19

Question 45

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

Answer 45

Efavirenz

Question 46

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

Answer 46

Nevirapine

Question 47

2 contraindications of NNRTIs

Answer 47

Efavirenz Nevirapine

Question 48

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

Answer 48

Protease inhibitors

Question 49

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

Answer 49

Protease inhibitors

Question 50

Protease inhibitors inhibits this

Answer 50

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

Question 51

Protease inhibitors have this action on CYP3A4

Answer 51

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

Question 52

Protease inhibitors are both substrate and inhibitors of this

Answer 52

CYP3A4

Question 53

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

Answer 53

Protease inhibitors

Question 54

2 common adverse effects of protease inhibitors

Answer 54

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

Question 55

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 55

Protease inhibitors

Question 56

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

Answer 56

PI-induced metabolism syndrome

Question 57

3 severe adverse effects of protease inhibitors

Answer 57

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

Question 58

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

Answer 58

Protease inhibitors

Question 59

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

Answer 59

Ritonavir

Question 60

Most potent CYP3A4 inhibitor of protease inhibitors

Answer 60

Ritonavir

Question 61

Ritonavir inhibits these

Answer 61

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

Question 62

Ritonavir is this class of anti-HIV drug

Answer 62

Protease inhibitor

Question 63

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

Answer 63

Ritonavir - tipranavir combination

Question 64

2 black box warnings of Tipranavir

Answer 64

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

Question 65

This adverse effect is most common with ritonavir - tipranavir combination

Answer 65

Intracranial hemorrhage

Question 66

Hepatotoxicity and intracranial hemorrhage are black box warnings of this

Answer 66

Tipranavir (PI)

Question 67

Enfuvirtide is in this class of anti-HIV drugs

Answer 67

Fusion inhibitor

Question 68

MOA of Enfuvirtide (fusion inhibitor)

Answer 68

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 69

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

Answer 69

Transmembrane glycoprotein subunit (GP41)

Question 70

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

Answer 70

Enfuvirtide (Fuseon)

Question 71

2 adverse effects of Enfuvirtide (fusion inhibitor)

Answer 71

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

Question 72

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 72

Maraviroc (CCR5 antagonist)

Question 73

Maraviroc MOA

Answer 73

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 74

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

Answer 74

CXCR4

Question 75

Black box warning of Maraviroc (CCR5 antagonist)

Answer 75

Hepatotoxicity

Question 76

3 adverse effects of Maraviroc (CCR5 antagonist)

Answer 76

Hypersensitivity Cardiovascular events (MIs, hypotension) Hepatotoxicity

Question 77

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

Answer 77

Thioridazine (antipsychotic)

Question 78

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

Answer 78

Integrase inhibitors

Question 79

3 adverse effects of integrase inhibitors

Answer 79

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

Question 80

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 80

Integrase inhibitors

Question 81

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 81

Ibalizumab

Question 82

MOA of ibalizumab

Answer 82

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

Question 83

Adverse effect of ibalizumab (CD4 post-attachment inhibitor)

Answer 83

Opportunistic infection susceptibility

Question 84

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

Answer 84

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

Question 85

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

Answer 85

Rapid resistance development Inferior antiretroviral activity

Question 86

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

Answer 86

Triple NRTI regimens

Question 87

Only exception when triple NRTI regimens can be used

Answer 87

Patients for whom other options are worse

Question 88

Integrase inhibitor that is approved as PrEP

Answer 88

Cabotegravir (Apretude)

Question 89

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

Answer 89

Integrase inhibitor

Question 90

2 drugs that are combinations of Emtricitabine and Tenofovir

Answer 90

Truvada and Descovy

Question 91

Truvada and Descovy are combinations of these 2 drugs

Answer 91

Emtricitabine and Tenofovir

Question 92

Truvada and Descovy are used as this

Answer 92

Pre-exposure prophylaxis (PrEP)

Question 93

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

Answer 93

Post-exposure prophylaxis (PEP)

Question 94

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

Answer 94

Integrase inhibitor

Question 95

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

Answer 95

Cobicistat (Tybost)