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HIV Flashcards

1
Q

Tenofovir Disoproxil (TDF) + emtricitabine (FTC)

A

Truvada
PrEP - preventative

Bone and kidney toxicity

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2
Q

Tenofovir Alafenamide (TAF + emtricitabine (FTC)

A

Descovy
PrEP - preventative
New in 2019, less toxicity

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3
Q

Cabotegravir for PrEP

A

Apretude
PrEP - preventative

1st long-acting injectable integrase inhibitor (q8 weeks)

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4
Q

Nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) MOA

A

Inhibit conversion of HIV RNA to DNA by blocking the function of reverse transcriptase

Inhibits RT at active site and terminates DNA chain

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5
Q

Second generation NRTI

A

Abacavir (ABC)
Emtricitabine (FTC)
Tenofovir disoproxil fumarate (TDF)

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6
Q

Third generation NRTI

A

Tenofovir alafenamide (TAF)

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7
Q

NRTI side effects

A

Inhibition of mitochondrial DNA functon and replication can lead to:

  • Lactic acidosis (rare, can occur at any time)
  • Hepatic steatosis
  • 1st gen associated with: peripheral neuropathy, lipodystrophy - may never resolve
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8
Q

Emtricitabine and Lamivudine general

A

Current backbone of recommended ART

Interchangable but NEVER use in conjunction

Active against hepB - when discontinuing in HIV + HepB patient, HBV rebound and worsening hepatitis can occur

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9
Q

Emtricitabine and lamivudine adverse effects

A

Most well tolerated NRTI
Rare: headache, nausea, fatigue

  • Require dosing adjustment with CrCl < 50mL/min
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10
Q

Triumeq

A

Abacavir + lamivudine + dolutegravir

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11
Q

Abacavir AE

A

Hypersensitivity syndrome: typically w/in 2-6 weeks initiation… fever, abdominal pain, and rash, fatal when re-challenged

Associated with HLA-B*5701 allele (test before starting abacavir)

Other: increased CVD risk in patients with underlying disease

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12
Q

Tenofovir formulations

A

Nucleotide adenosine 5i-monophosphate derivative

Tenofovir disoproxil fumarate (TDF): decreases bone mineral density, decrease CrCl over time, fanconi syndrome (rare)

Tenofovir alafenamide (TAF): greater antiviral activity, lower dosing allowing for decrease in AE

TAF > TDF (rather have an A, than a D)

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13
Q

Truvada

A

TDF + emtricitabine

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14
Q

Descovy

A

TAF + emtricitabine

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15
Q

Non-Nucleoside reverse transcriptase inhibitors (NNRTIs) MOA

A

Inhibit conversion of HIV RNA to DNA by blocking function of reverse transcriptase

Binds RT at non-active site

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16
Q

Describe resistance in NNRTI

A

low barrier of resistance - single point mutation in RT can inactivate all members of class (some exceptions)

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17
Q

NNRTI drug interactions

A

CYP450 substrates, some also inducers/inhibitors

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18
Q

NNRTI adverse effects

A

Hypersensitivity reactions (rash), increased liver enzymes, diarrhea, pruritis

neurological/psychiatric (efavirenz&raquo_space;> etravirine&raquo_space; rilpivirine > doravirine)

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19
Q

first generation NNRTIs

A

Nevirapine
Efavirenz*
Delavirdine

Mod-high potentcy, some treatment failure, most common. resistance mutation: K103N

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20
Q

second generation NNRTIs

A

Etravirine
Rilpivirine*
Doravirine

higher potency, rarely associated with treatment failure, no effect of K103N

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21
Q

Efavirenz

A

Neuropsychiatric AE: vivid dreams, insomnia, hallucinations, dizziness, difficult concentrating, suicidal ideation
Teratogenic
Hepatotoxicity
Rash - maculopapular to SJS and TEN

Not used as much anymore

22
Q

Efavirenz drug interactions

A

CYP3A4 substrates (carbamazepine, posaconazole)

23
Q

Rilpivirine general

A

Well tolerated (fewer AE than efavirenz) but not as potent

More failures when Vl > 100,000 or CD4+ <200

24
Q

Rilpivirine drug interactions + other

A

Plasma concentrations influenced by various CYP enzymes - protease inhibitors and azole antifungals increase plasma RPV levels

CI with strong CYP3A4 inducers

Needs ACIDIC environment for absorption (PPI are CI; can do H2 receptor antagonist at least 12 hours before)

25
Odefesy
TAF + emtricitabine + rilpivirine
26
Juluca
Rilpivirine + dolutegravir
27
Cabenuva
Rilpivirine + cabotegravir
28
Protease inhibitors MOA
Inhibition of HIV protease enzyme, preventing formation and release of mature virons High barrier to resistance, potent viral efficacy Need pharmacokinetic booster
29
Third generation PI
Atazanavir Darunavir As go from first --> 3rd, decrease in AE: lipodystrophy, N/V, diarrhea, cholesterolemia, insulin resistance
30
Protease Inhibitors AE
Most common with 1st gen (ritonavir, indinavir, saquinavir, nelfinavir) ``` GI intolerance: N/V, diarrhea Lipodystrophy: long term complications resulting from metabolic and morphologic abnormalities (fat atrophy and deposition) Lipid abnormalities (hypertriglyceridemia, cholesterolemia, lipoaccumulation - lopinvair/ritonavir highest risk) ```
31
Protease inhibitors class effects
Cardiovascular risk: dyslipidemia, insulin resistance, atherosclerosis, myocardial infarction Major drug interactions due to booster (CYP3A4, CYP2D6) Food effects bioavailability
32
boosted protease inhibitor regimens
addition of booster --> inhibition of CYP34A --> reduced metabolism of PI --> lower dosing frequency/better blood concentrations boosters: ritonavir or cobicistat
33
Atazanavir
Don't use with hepatic impairment take with food needs acidic environment CI with CYP34A usually active in patients who have failed other PI
34
Atazanavir adverse effects
N/V/D hyperbilirubinemia +/- jaundice or scleral icterus nephrolithiasis + cholelithiasis lower cardio risk vs other PI
35
Darunavir
Can be considered alternative first line treatment in some treatment naive AE: well tolerated, favorable lipid profile compared to other PI, possible higher CVD risk vs atazanavir drug-drug: CYP34A
36
Symtuza
darunavir-cobicistat-TAF-emtricitabine
37
Prezcobix
darunivir-cobicistat
38
Integrase strand transfer inhibitors (INSTIs) MOA
prevents the insertion of DNA (transcribed from the virus) into human cell DNA by inhibiting integrase enzyme
39
first gen INSTI
Raltegravir | Elvitegravir
40
second gen INSTI
Dolutegravir | Bictegravir
41
third gen INSTI
cabotegravir
42
Raltegravir
twice day dosing (use declining) | found to be inferior to dolutegravair
43
elvitegravir
can only get in combo pills: stribild, genvoya some nausea, diarrhea MAJOR 34A inhibitor resistance may infer cross resistance w/ raltegravir
44
Dolutegravir
Preferred INSTI AE: decreases tubular secretion of creatinine, weight gain, neuropsychiatric effects (depression, anxiety, sleep disturbances), neural tube defects?
45
Bictegravir
First-line recommendation! high barrier to resistance, small single tablet, well-tolerated Biktarvy: bictegravir + emtricitabine + TAF
46
cabotegravir
long-acting injectable in combo with injectable rilpivirine (Cabenuva) - monthly injection extended release injectable (apretude) - q8 week injection for PrEP
47
entry inhibitors
Subclasses CD4 post-attachment inhibitor CCR5 coreceptor antagonist Fusion inhibitors
48
Fusion inhibitors
Enfuviritide (Fuzeon) - binds to gp41 and prevents attachment of HIV virus to T-cell AE: injection site reactions, sclerotic lesions
49
monitoring ART
measure HIV RNA (viral load): prior to start, 4-6 weeks after initiation, every 1-2 months, every 3-6 months, etc.. as viral load decreases GOAL: undetectable at 16-24 weeks. measuure CD4 count: monitor every 3-6 months GOAL: increase by 50-150 in 1st year
50
PEP
3 drug regimen preferred - TDF/FTC + RAL (occupational) - Truvada + Isentress or Tivicay (nonoccupational) Reasonable to substitute TAF or other INSTI Duration: 4 weeks

obgyn (14 decks)

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