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
HIV Replication Stage 7 (Budding and Maturation) Drugs
Protease Inhibitors (PIs)- atazanavir, darunavir
26
CD4 count
The major indicator of immune function used to determine the need for OI prophylaxis
27
HIV viral load
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.
28
Treatment goal of HIV
Undetectable HIV viral load
29
HIV Routine labs
CD4 count, HIV viral load, drug resistance, CMP, HepB and HepC, pregnancy, HLAB5701 if abacavir, tropism assay if maraviroc
30
Biktarvy
Bictegravir/ Emtricitabine/ Tenofovir alafenamide
31
Triumeq
Dolutegravir/ Abacavir/ Lamivudine
32
Dovato
Dolutegravir/ Lamivudine
33
Tivicay
Dolutegravir
34
Truvada
Emtricitabine/ TDF
35
Descovy
Emtricitabine/ TAF
36
Preferred Initial ART regimen
Single tablet, once daily- Biktarvy, Triumeq, Dovato Two pills, QD- Tivicay + Truvada, Tivicay + Descovy
37
Most preferred HIV regimens contain
2 NRTIs and 1 INSTI
38
When should you not use Dovato?
Treatment naive patients if HIV RNA >500,000 copies/mL, there is a known hep B virus, or HIV genotypic testing is unavailable.
39
Abacavir testing
HLA-B*5701 allele. A positive result indicates a higher risk of severe hypersensitivty reaction and any abacavir containing product is contraindicated.
40
Complete HIV ART Regimen
Has one "base" plus two NRTIs. The base can be a PI, NNRTI, or INSTI
41
NRTIs drugs
Abacavir, emtricitabine, lamivudine, tenofovir disoproxil fumarate (TDF), tenofovir alafenamide (TAF), zidovudine, didanosine, stavudine
42
INSTI drugs
Bictegravir, Dolutegravir, Elvitegravir, Raltegravir
43
NNRTI drugs
efavirenz, rilpivirine
44
PI drugs
Atazanavir, Darunavir
45
Pharmacokinetic boosters
Ritonavir, Cobicistat
46
CCR5 antagonist
Maraviroc (Selzentry)
47
Attachment inhibitor
Fostemsavir
48
Post-attachment inhibitor
Ibalizumab
49
Fusion inhibitor
Enfuvirtide
50
INSTI-based regimens
Biktarvy, Triumeq, Dovato, Stribild, Genvoya
51
NNRTI based regimens
Atripla, Complera, Odefsey
52
Epzixom
Abacavir/ Lamivudine
53
MOA of NRTIs
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
NRTIs barrier to resistance
Low barrier to resistance (resistance develops easily)
55
All NRTIs except abacavir
Decrease dose with renal impairment
56
How many times a day is tenofovir?
QD
57
How many times a day is zidovudine
twice
58
All NRTI warnings
Lactic acidosis and hepatomegaly with steatosis (fatty liver); BBW for didanosine, stavudine, and zidovudine
59
NRTIs common AE
nausea, diarrhea, headache, increased LFTs
60
HBV and HIV coninfection BBW
BBW for NRTIs Severe acute HBV exacerbation can occur if emtricitabine, lamivudine, or tenofovir containing products are discontinued (some NRTIs treat HBV).
61
Abacavir BBW
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
Avoid abacavir with
CVD due to potential to increase risk of MI
63
Emtricitabine AE
hypersensitivity of the palms of the hands or soles of the feet.
64
Tenofovir formulations AE
Renal impairment Decreased bone mineral density- consider vitamin d and calcium supplementation
65
What to monitor if switching from TDF to TAF?
Lipids (TAF is associated with a higher risk of lipid abnormalities)
66
Zidovudine AE
Hematologic toxicity- neutropenia and anemia (increased MCV is a sign of adherence) Myopathy
67
Didanosine and stavudine AE
Pancreatitis, peripheral neuropathy (can be irreversible)
68
INSTI MOA
Block the integrase enzyme, preventing HIV DNA from inserting into the host cell DNA in stage 4 (integration) of the HIV life cycle.
69
INSTI barrier to resistance
Have a higher barrier of resistance than NRTIs and NNRTIs
70
INSTI generic names end in
-tegravir
71
Which INSTIs are given twice daily?
Isentress, Tivicay (treatment-experienced patients, those with INSTI resistance or those taking UGT1A1 or CYP2A4 inducers)
72
Stribild CrCl
CrCl <70- do not start
73
Biktarvy and Genvoya CrCl
CrCl <30- so not start
74
Bicitegravir and dolutegravir AE
Increased SCr (by inhibiting tubular secretion) with no effect on GFR
75
Raltegravir AE
Increased CPK, myopathy, and rhabdomyolysis
76
Elvitegravir AE
proteinuria
77
Dolutegravir AE
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
AE of all INSTIs
HA, insomnia, diarrhea, weight gain, rare risk of depression and suicidal ideation in patients with preexisting psychiatric conditions (except bictegravir)
79
INSTIs DDI
Polyvalent cations Separate 2 hours before or 6 hours after Al, ca, Mg, and Fe containing products.
80
NNRTIs MOA
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
NNRTIs barrier of resistance
Lower than INSTIs or PIs
82
Rilpivirine admin
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
Efavirenz admin
Food increases the bioavailability and risk for CNS effects. Take on an empty stomach QHS to decrease (and sleep through) CNS effects
84
All NNRTIs AE
Hepatotoxicity and rash/severe rash, including SJS/TEN: Highest risk with nevirapine
85
Efavirenz AE
Psychiatric symptoms (depression, suicidal thoughts) CNS effects (impaired concentration, abnormal dreams, confusion), generally resolve in 2-4 weeks Increased total cholesterol and triglycerides
86
DDI of all NNRTIs
All NNRTIs are major CYP3A4 substrates (and some are substrates of other CYP enzymes)
87
DDI of Rilpivirine
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
DDI of doravirine
Major CYP3A4 substrate Do not use with strong CYP3A4 inducers (carbamazepine, oxcarbazempine, phenobarbital, phenytoin, rifampin, rifapentine, St. Johns wort)
89
DDI of Efavirenz and etravirine
Major CYP3A4 substrate Moderate CYP3A4 inducers (many drug interactions)
90
Rilpivirine AE
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
Protease inhibitor MOA
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
PIs barrier of resistance
PIs (especially darunavir) have a higher barrier to resistance
93
PI generic names end in
-navir
94
All PIs are recommended to take
with a booster (ritonavir or cobicistat)
95
All PIs renal dose adjustment
No renal dose adjustment
96
All PIs admin
Take with food to decrease GI upset except: Fosamprenavir oral solution take without food Lopinavir/ritonavir tablets take with or without food
97
Atazanavir admin
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
Ritonavir admin
Only used for pharmacokinetic boosting
99
All PIs common AE
Diarrhea, nausea
100
All PIs metabolic abnormalities
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
All PIs hepatic dysfunction
Increased LFTs, hepatitis (highest risk with tipranavir), and/or exacerbation of preexisting hepatic disease
102
All PIs hypersensitivity reactions
Rash (including SJS/TEN), bronchospasm, angioedema, anaphylaxis
103
Atazanavir AE
Hyperbilirubinemia (jaundice or scleral icterus, remember with "bananavir" Reversible- does not require discontinuation
104
Darunavir, Fosamprenavir, Tipranavir caution
Caution with sulfa allergy
105
Lopinavir/Ritonavir oral solution
contains 42% alcohol- can cause disulfiram reaction if taken with metronidazole
106
Tipranavir AE
Intracranial hemorrhage
107
PIs CYP3A4 DDI
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
Protease inhibitors metabolic syndrome
Decreased HDL Increased LDL and TG Increased BG Insulin resistance Abdominal adiposity
109
Pharmacokinetic boosters
Ritonavir (difficult to co-formulate) Cobicistat- can be co-formulated
110
Ritonavir dose
100-400 mg PO QD with food
111
Cobicistat dose
150 mg PO daily with the boosted drug and with food
112
PI booster MOA
Ritonavir and cobicistat are inhibitors of CYP3A4. They inhibit ART metabolism, which increases (boosts) the ART level and therapeutic effect.
113
Are ritonavir and cobicistat interchangeable?
No, do not use both together
114
Ritonavir and cobicistat booster DDI
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
CCR5 Antagonist MOA
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
Maraviroc safety issues
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
Maraviroc baseline testing
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
Attachment inhibitor (Fostemsavir) MOA
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
Fostemsavir safety issues
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
When is fostemsavir indicated?
Indicated in combination with other ARTs in heavily treatment- experienced patients who are failing current therapy