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1. NAPLEX Prep > HIV > Flashcards

HIV Flashcards

1
Q

What is HIV?

A

Single stranded RNA retrovirus that uses the machinery in host CD4 T helper cells to replicate. Once replicated, the viral copies burst through the CD4 membrane, destroying the cell in the process. Billions of T cells are destroyed every day if HIV is not treated adequately.

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2
Q

When HIV continues to replicate

A

the viral load increases and the CD4 count decreases

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3
Q

AIDS is diagnosed when

A

CD4 falls below 200cells/mm3 or the patient develops an AIDS defining condition

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4
Q

HIV transmission

A

Blood, semen, vaginal secretions, rectal secretions, or ingestion of breast milk.
Most infections are caused by unprotected vaginal or rectal sex and sharing injection drug equipment.

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5
Q

Vertical transmission

A

Mother to child transmission
HIV can spread from woman to child during pregnancy, childbirth, breastfeeding.

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6
Q

Screening of HIV

A

All patients 13-64 need to be screened at least once.
If a person is high risk, annual screening should be conducted
High risk- sharing drug equipment, high risk sexual behavior, h/o sexually transmitted infections, h/o hepatitis or TB infection.

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7
Q

Acute HIV infection

A

Presents with non-specific flu like symptoms that can last a few days to several weeks

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8
Q

What happens about 2 weeks after infection?

A

the viral load is high enough for HIV RNA and HIV p24 antigens to be detected with an initial HIV1/HIV2 antigen/antibody screening test.

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9
Q

What do you do if an HIV antigen/antibody immunoassay is positive?

A

Confirm with antibody differentiation immunoassay. If positivem HIV confirmed.
If negative, quantify the viral load with an HIV1 nucleic acid test

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10
Q

OTC HIV testing

A

OraQuick detects the presence of HIV antibodies and provides intermediate results. If positive, it must be followed up with a confirmatory test.
These tests should be used >3 months from exposure due to the lag in antibody production. Testing sooner can cause a false negative result.

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11
Q

HIV replication stages

A

Stage 1.) Binding/Attachment
Stage 2.) Fusion
Stage 3.) Reverse Transcription
Stage 4.) Integration
Stage 5.) Replication
Stage 6.) Assembly
Stage 7.) Budding and Maturation

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12
Q

HIV Replication Stage 1 (Binding/Attachment)

A

HIV attaches to a CD4 receptor and the CCR5 and/or CXCR4 coreceptors on the surface of the CD4 host cell.

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13
Q

HIV Replication Stage 1 (Binding/Attachment) Drugs

A

CCR5 antagonist- maraviroc
Attachment inhibitor- fostemsavir
Post-attachment inhibitor- ibalizumab

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14
Q

HIV Replication Stage 2 (Fusion)

A

The HIV viral envelope fuses with the CD4 cell membrane. HIV enters the host cell and releases HIV RNA, viral proteins and enzymes needed for replication

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15
Q

HIV Replication Stage 2 (Fusion) Drugs

A

Fusion inhibitor: enfuvirtide

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16
Q

HIV Replication Stage 3 (Reverse Transcription)

A

HIV RNA is converted to HIV DNA by reverse transcriptase (an HIV enzyme). HIV DNA can then enter the CD4 cell nucleus

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17
Q

HIV Replication Stage 3 (Reverse Transcription) Drugs

A

Nucleoside reverse transcriptase inhibitors (NRTIs)- emtricitabine, tenofovir
Non-nucleoside reverse transcriptase inhibitors (NNRTIs)- efavirenz, rilpivirine

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18
Q

HIV Replication Stage 4 (Integration)

A

Once inside the CD4 cell nucleus, integrase (an HIV enzyme) is released and used to insert HIV DNA into the host cell DNA

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19
Q

HIV Replication Stage 4 (Integration) Drugs

A

Integrase Strand Transfer Inhibitor (INSTIs)- bictegravir, dolutegravir, raltegravir

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20
Q

HIV Replication Stage 5 (Replication)

A

Host cell machinery is used to transcribe and translate HIV DNA into HIV RNA and long chain proteins (the HIV building blocks)

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21
Q

HIV Replication Stage 5 (Replication) Drugs

A

None

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22
Q

HIV Replication Stage 6 (Assembly)

A

New HIV RNA, proteins, and enzymes (including protease) move to the cell surface and assemble into immature HIV

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23
Q

HIV Replication Stage 6 (Assembly) Drugs

A

None

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24
Q

HIV Replication Stage 7 (Budding and Maturation)

A

Immature HIV pushes out of the CD4 cell and protease (an HIV enzyme) breaks up the long viral protein chains, creating mature virus that can infect other cells

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25
Q

HIV Replication Stage 7 (Budding and Maturation) Drugs

A

Protease Inhibitors (PIs)- atazanavir, darunavir

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26
Q

CD4 count

A

The major indicator of immune function used to determine the need for OI prophylaxis

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27
Q

HIV viral load

A

Indicates how much HIV RNA is in the blood. It is the most important indicator of response to ART. A high viral load can be due to medication nonadherence or drug resistance.

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28
Q

Treatment goal of HIV

A

Undetectable HIV viral load

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29
Q

HIV Routine labs

A

CD4 count, HIV viral load, drug resistance, CMP, HepB and HepC, pregnancy, HLAB5701 if abacavir, tropism assay if maraviroc

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30
Q

Biktarvy

A

Bictegravir/ Emtricitabine/ Tenofovir alafenamide

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31
Q

Triumeq

A

Dolutegravir/ Abacavir/ Lamivudine

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32
Q

Dovato

A

Dolutegravir/ Lamivudine

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33
Q

Tivicay

A

Dolutegravir

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34
Q

Truvada

A

Emtricitabine/ TDF

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35
Q

Descovy

A

Emtricitabine/ TAF

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36
Q

Preferred Initial ART regimen

A

Single tablet, once daily- Biktarvy, Triumeq, Dovato
Two pills, QD- Tivicay + Truvada, Tivicay + Descovy

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37
Q

Most preferred HIV regimens contain

A

2 NRTIs and 1 INSTI

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38
Q

When should you not use Dovato?

A

Treatment naive patients if HIV RNA >500,000 copies/mL, there is a known hep B virus, or HIV genotypic testing is unavailable.

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39
Q

Abacavir testing

A

HLA-B*5701 allele. A positive result indicates a higher risk of severe hypersensitivty reaction and any abacavir containing product is contraindicated.

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40
Q

Complete HIV ART Regimen

A

Has one “base” plus two NRTIs. The base can be a PI, NNRTI, or INSTI

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41
Q

NRTIs drugs

A

Abacavir, emtricitabine, lamivudine, tenofovir disoproxil fumarate (TDF), tenofovir alafenamide (TAF), zidovudine, didanosine, stavudine

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42
Q

INSTI drugs

A

Bictegravir, Dolutegravir, Elvitegravir, Raltegravir

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43
Q

NNRTI drugs

A

efavirenz, rilpivirine

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44
Q

PI drugs

A

Atazanavir, Darunavir

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45
Q

Pharmacokinetic boosters

A

Ritonavir, Cobicistat

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46
Q

CCR5 antagonist

A

Maraviroc (Selzentry)

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47
Q

Attachment inhibitor

A

Fostemsavir

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48
Q

Post-attachment inhibitor

A

Ibalizumab

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49
Q

Fusion inhibitor

A

Enfuvirtide

50
Q

INSTI-based regimens

A

Biktarvy, Triumeq, Dovato, Stribild, Genvoya

51
Q

NNRTI based regimens

A

Atripla, Complera, Odefsey

52
Q

Epzixom

A

Abacavir/ Lamivudine

53
Q

MOA of NRTIs

A

Competitively inhibit the reverse transcriptase enzyme, preventing the conversion of HIV RNA to HIV DNA in stage 3 (reverse transcription) of the HIV life cycle

54
Q

NRTIs barrier to resistance

A

Low barrier to resistance (resistance develops easily)

55
Q

All NRTIs except abacavir

A

Decrease dose with renal impairment

56
Q

How many times a day is tenofovir?

A

QD

57
Q

How many times a day is zidovudine

A

twice

58
Q

All NRTI warnings

A

Lactic acidosis and hepatomegaly with steatosis (fatty liver); BBW for didanosine, stavudine, and zidovudine

59
Q

NRTIs common AE

A

nausea, diarrhea, headache, increased LFTs

60
Q

HBV and HIV coninfection BBW

A

BBW for NRTIs
Severe acute HBV exacerbation can occur if emtricitabine, lamivudine, or tenofovir containing products are discontinued (some NRTIs treat HBV).

61
Q

Abacavir BBW

A

Hypersensitivity reaction
Screen for HLA-B*5701 allele before starting. Abacavir is contraindicated if positive.
Patients have to carry a medication cared indicating that HSR is an emergency.
Never rechallenge with a h/o HSR

62
Q

Avoid abacavir with

A

CVD due to potential to increase risk of MI

63
Q

Emtricitabine AE

A

hypersensitivity of the palms of the hands or soles of the feet.

64
Q

Tenofovir formulations AE

A

Renal impairment
Decreased bone mineral density- consider vitamin d and calcium supplementation

65
Q

What to monitor if switching from TDF to TAF?

A

Lipids (TAF is associated with a higher risk of lipid abnormalities)

66
Q

Zidovudine AE

A

Hematologic toxicity- neutropenia and anemia (increased MCV is a sign of adherence)
Myopathy

67
Q

Didanosine and stavudine AE

A

Pancreatitis, peripheral neuropathy (can be irreversible)

68
Q

INSTI MOA

A

Block the integrase enzyme, preventing HIV DNA from inserting into the host cell DNA in stage 4 (integration) of the HIV life cycle.

69
Q

INSTI barrier to resistance

A

Have a higher barrier of resistance than NRTIs and NNRTIs

70
Q

INSTI generic names end in

A

-tegravir

71
Q

Which INSTIs are given twice daily?

A

Isentress, Tivicay (treatment-experienced patients, those with INSTI resistance or those taking UGT1A1 or CYP2A4 inducers)

72
Q

Stribild CrCl

A

CrCl <70- do not start

73
Q

Biktarvy and Genvoya CrCl

A

CrCl <30- so not start

74
Q

Bicitegravir and dolutegravir AE

A

Increased SCr (by inhibiting tubular secretion) with no effect on GFR

75
Q

Raltegravir AE

A

Increased CPK, myopathy, and rhabdomyolysis

76
Q

Elvitegravir AE

A

proteinuria

77
Q

Dolutegravir AE

A

HSR with severe rash and organ dysfunction, including hepatotoxicity
Small risk of neural tube defects in a developing fetus (though still a preferred option in pregnancy)
Increased CPK, myalgia

78
Q

AE of all INSTIs

A

HA, insomnia, diarrhea, weight gain, rare risk of depression and suicidal ideation in patients with preexisting psychiatric conditions (except bictegravir)

79
Q

INSTIs DDI

A

Polyvalent cations
Separate 2 hours before or 6 hours after Al, ca, Mg, and Fe containing products.

80
Q

NNRTIs MOA

A

Non-competitively inhibit the reverse transcriptase enzyme, preventing the conversion of HIV RNA to HIV DNA in stage 3 (reverse transcriptase) of the HIV life cycle.

81
Q

NNRTIs barrier of resistance

A

Lower than INSTIs or PIs

82
Q

Rilpivirine admin

A

Take with a meal and water (do not substitute with protein drink)
Requires an acidic environment for abs. Do NOT use with PPIs and separate from H2RAs and antacids

83
Q

Efavirenz admin

A

Food increases the bioavailability and risk for CNS effects. Take on an empty stomach QHS to decrease (and sleep through) CNS effects

84
Q

All NNRTIs AE

A

Hepatotoxicity and rash/severe rash, including SJS/TEN: Highest risk with nevirapine

85
Q

Efavirenz AE

A

Psychiatric symptoms (depression, suicidal thoughts)
CNS effects (impaired concentration, abnormal dreams, confusion), generally resolve in 2-4 weeks
Increased total cholesterol and triglycerides

86
Q

DDI of all NNRTIs

A

All NNRTIs are major CYP3A4 substrates (and some are substrates of other CYP enzymes)

87
Q

DDI of Rilpivirine

A

Major CYP3A4 substrate
Do not use with strong CYP3A4 inducers (carbamazepine, oxcarbazempine, phenobarbital, phenytoin, rifampin, rifapentine, St. Johns wort)
DO NOT use with PPIs
Separate H2RAs at least 12 hours before or 4 hours after rilpivirine.
Take antacids at least 2 hours before or 4 hours after rilpivirine

88
Q

DDI of doravirine

A

Major CYP3A4 substrate
Do not use with strong CYP3A4 inducers (carbamazepine, oxcarbazempine, phenobarbital, phenytoin, rifampin, rifapentine, St. Johns wort)

89
Q

DDI of Efavirenz and etravirine

A

Major CYP3A4 substrate
Moderate CYP3A4 inducers (many drug interactions)

90
Q

Rilpivirine AE

A

Depression
Increased SCr with no effect on GFR
Do not use if viral load >100,000 copies/mL and/or CD4 count <200 cells/mm3 (higher failure rate)

91
Q

Protease inhibitor MOA

A

Inhibit the HIV protease enzyme, preventing long viral protein chains from being broken down into the smaller chains needed to produce mature (infectious) virus in stage 7 (budding and maturation) of the HIV life cycle; HIV continues to replicate, but produces immature virions that are not infectious

92
Q

PIs barrier of resistance

A

PIs (especially darunavir) have a higher barrier to resistance

93
Q

PI generic names end in

A

-navir

94
Q

All PIs are recommended to take

A

with a booster (ritonavir or cobicistat)

95
Q

All PIs renal dose adjustment

A

No renal dose adjustment

96
Q

All PIs admin

A

Take with food to decrease GI upset except:
Fosamprenavir oral solution take without food
Lopinavir/ritonavir tablets take with or without food

97
Q

Atazanavir admin

A

Needs an acidic gut for absorption
Take atazanavir 2 hours before or 1 hour after antacids
Avoid H2RAs or take atazanavir 2 hours before or 10 hours after H2RAs
Avoid PPIs with unboosted atazanavir; take boosted atazanavir at least 12 hours after the PPI

98
Q

Ritonavir admin

A

Only used for pharmacokinetic boosting

99
Q

All PIs common AE

A

Diarrhea, nausea

100
Q

All PIs metabolic abnormalities

A

Hyperglycemia/ insulin/resistance, dyslipidemia (increased LDL, Increased TGs), increased body fat and lipodystrophy
PIs increase CVD risk (lower risk with atazanavir and darunavir, higher risk with lopinavir/ritonavir)

101
Q

All PIs hepatic dysfunction

A

Increased LFTs, hepatitis (highest risk with tipranavir), and/or exacerbation of preexisting hepatic disease

102
Q

All PIs hypersensitivity reactions

A

Rash (including SJS/TEN), bronchospasm, angioedema, anaphylaxis

103
Q

Atazanavir AE

A

Hyperbilirubinemia (jaundice or scleral icterus, remember with “bananavir”
Reversible- does not require discontinuation

104
Q

Darunavir, Fosamprenavir, Tipranavir caution

A

Caution with sulfa allergy

105
Q

Lopinavir/Ritonavir oral solution

A

contains 42% alcohol- can cause disulfiram reaction if taken with metronidazole

106
Q

Tipranavir AE

A

Intracranial hemorrhage

107
Q

PIs CYP3A4 DDI

A

All PIs are major CYP3A4 substrates and most are strong CYP3A4 inhibitors
Do not use the following drugs with any PIs:
alfuzosin, colchicine, dronedarone, lovastatin and simvastatin, CYP3A4 inducers (carbamazepine, phenytoin, phenobarbital, rifampin, St. Johns wort)
Anticoagulants/antiplatelets
Direct acting antivirals for hepatitis C
Some hormonal contraceptives
Steroids

108
Q

Protease inhibitors metabolic syndrome

A

Decreased HDL
Increased LDL and TG
Increased BG
Insulin resistance
Abdominal adiposity

109
Q

Pharmacokinetic boosters

A

Ritonavir (difficult to co-formulate)
Cobicistat- can be co-formulated

110
Q

Ritonavir dose

A

100-400 mg PO QD with food

111
Q

Cobicistat dose

A

150 mg PO daily with the boosted drug and with food

112
Q

PI booster MOA

A

Ritonavir and cobicistat are inhibitors of CYP3A4. They inhibit ART metabolism, which increases (boosts) the ART level and therapeutic effect.

113
Q

Are ritonavir and cobicistat interchangeable?

A

No, do not use both together

114
Q

Ritonavir and cobicistat booster DDI

A

Strong inhibitors of CYP3A4 and they also inhibit CYP2D6, P-gp transporters and some of the OAT family of transporters
Contraindicated drugs- alfuzosin, tamsulosin, colchicine, lovastatin, simvastatin, azole antifungals, cardiovascular drugs (amiodarone, dronedarone, eplerenone, ivabradine, ranolazine)
PDE-5 inhibitors
Many tyrosine kinase inhibitors (“nibs”)
CYP3A4 inducers- carbamazepine, phenytoin, phenobarbital, rifampin, St.Johns wort
Anny narrow therapeutic index drug that is highly dependent on CYP3A4 for clearance

115
Q

CCR5 Antagonist MOA

A

Blocks HIV from binding (and subsequently entering) the CD4 cell in virus strains that use the CCR5 co-receptor in stage 1 of the HIV life cycle (binding/attachment)

116
Q

Maraviroc safety issues

A

Hepatotoxicity (BBW), hypersensitivity reactions (including SJS/TEN), CV events (including MI), orthostatic hypotension in patients with renal impairment
Do not use if severe renal impairment (CrCl<30 mL/min) and taking potent 3A4 inhibitors/inducers)

117
Q

Maraviroc baseline testing

A

must have tropism assay results before starting (tropism test determines if the HIV strain infecting the patient can only bind to the CCR5 co-receptor)
If the HIV strain can bind to CXCR4 or mixed co receptors maraviroc will not work and HIV will still be able to enter the CD4 cell

118
Q

Attachment inhibitor (Fostemsavir) MOA

A

Converted to temsavir (active form), which binds to the gp120 subunit of HIV envelope proteins, inhibiting the interaction between teh virus and the CD4 host cell in stage 1 of the HIV life cycle (binding/attachment)

119
Q

Fostemsavir safety issues

A

Do not use with strong CYP3A4 inducers
Must maintain effective HBV treatment in patients coinfected with HBV
Can increase SCr (higher risk if underlying renal disease)

120
Q

When is fostemsavir indicated?

A

Indicated in combination with other ARTs in heavily treatment- experienced patients who are failing current therapy

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