E5 HIV/AIDS - Kleyn

Question 1

what does glycoprotein 120 (gp120) bind to?

Answer 1

CD4 receptors on T cells, macrophages, and dendritic cells

Question 2

what is the primary target cell of HIV?

Answer 2

CD4 T helper/inducer lymphocyte

Question 3

most common transmission method of HIV

Answer 3

sexual duh

Question 4

3 stages of HIV infection

Answer 4

1. acute retroviral syndrome
2. chronic HIV infection (asymptomatic)
3. acquired immunodeficiency syndrome (AIDS) (symptomatic)

Question 5

when should you recc screening in pregnant women?

Answer 5

as early as possible each pregnancy, maybe repeat in 3rd trimester

Question 6

all pts initiating tx for ________ should be screened

Answer 6

TB

Question 7

2 ways to diagnose HIV

Answer 7

• • results from a multitest algorithm
• • virologic test (viral load, qualitative HIV NAT)

Question 8

OTC HIV rapid test counseling:
- pts w/ reactive results -> ?
- pts with non-reactive results -> ?
** LO

Answer 8

• reactive -> seek out medical provider for confirmatory testing
• non-reactive -> counsel on the seroconversion window (3 months for oraquick), repeat test if risk event occurred within window period, methods of risk reduction and prevention (didnt give details on that last one)

Question 9

2 HIV surrogate markers:

Answer 9

• CD4 T lymphocyte cell count
• HIV RNA PCR (viral load)

Question 10

CD4 count by stage:
stage 0:
stage 1:
stage 2:
stage 3:

Answer 10

0: independent criteria
1: >500
2: 200-499
3: <200 (AIDS or OI)

Question 11

MOA of nucelos(t)ide reverse transcriptase inhibitors:

Answer 11

Synthetic purine and pyrimidine analogues which result in elongation termination of growing proviral DNA chain

Question 12

class adverse effects:
nucelos(t)ide reverse transcriptase inhibitors

Answer 12

• mitochondrial toxicity and lactic acidosis w/ or w/out hepatomegaly and hepatic steatosis

Question 13

2 precautions and interactions w/ nucelos(t)ide reverse transcriptase inhibitors

Answer 13

-require dose adjustment in renal insufficiency (except abacavir)
- few clinically significant drug interactions

Question 14

MOA of Non-Nucleos(t)ide Reverse Transcriptase Inhibitors:

Answer 14

Bind to an allosteric site of the reverse transcriptase enzyme reducing functionality

Question 15

class adverse effects for Non-Nucleos(t)ide Reverse Transcriptase Inhibitors (1)

Answer 15

rash

Question 16

precautions and interactions w/ Non-Nucleos(t)ide Reverse Transcriptase Inhibitors (3)

Answer 16

• use w/ caution in hepatic impairment
• many DDI exist
• high-level resistance develops easily and quickly (especially nevirapine and efavirenz)

Question 17

MOA of protease inhibitors:

Answer 17

inhibit action of viral protease preventing the assembly, maturation, and release of new virons

Question 18

class adverse effects for protease inhibitors: (3)

Answer 18

• GI intolerance
• insulin resistance
• lipodystrophy

Question 19

precautions and interactions with protease inhibitors: (3)

Answer 19

• many are not recommended in severe hepatic impairment
• many, many significant drug interactions
• highly favorable resistance profile, but greater pill burden

Question 20

what two medications are used for “boosting” in low doses to pharmacokinetically enhance the concentration of other ARVS, how do they do this?

Answer 20

• ritonavir, cobicistat
• super potent inhibitors of CYP3A4

Question 21

anti-HIV activity seen at doses of 600mg BID:
A. cobicistat
B. ritonavir

Answer 21

A

Question 22

MOA of Integrase Strand Transfer Inhibitors (INSTIs)

Answer 22

inhibit HIV integrase, preventing the proviral DNA integration into the host cell genome

Question 23

class adverse effect for Integrase Strand Transfer Inhibitors (INSTIs)

Answer 23

weight gain

Question 24

2 precautions and interactions for Integrase Strand Transfer Inhibitors (INSTIs)

Answer 24

• fewer drug interactions than the others (except elvitegravir)
• resistance can develop easily to 1st gen INSTIs, but 2nd gen INSTIs have a resistance profile on par w/ boosted- PI’s

Question 25

which 2 are 1st gen INSTI's A. Raltegravir B. Dolutegravir C. Elvitegravir D. Bictegravir

Answer 25

A + C

Question 26

Attachment inhibitor: - fostemsavir is a prodrug of ________ - _______ binds to gp120 on surface of HIV, blocking attachment to the CD4 T-cell co=receptor

Answer 26

Temsavir (which one do you actually use tf)

Question 27

2 precautions and interactions for Attachment inhibitor

Answer 27

- CI w/ strong 3A4 inducers as co-administration results in significant decreases in temsavir conc. - rarely used clinically (great)

Question 28

okay im skipping the post-attachment inhibitors too because i dont think theyre important either

Answer 28

okay

Question 29

MOA of chemokine coreceptor 5 (CCR5) Antagonist:

Answer 29

- binds to CCR5 (or CXCR4) on the CD4 cell surface, blocks the binding of gp120 and prevents entry of HIV into the host cell (cool)

Question 30

2 precautions and interactions for CCR5 antagonists

Answer 30

- before tx can be considered, a tropism assay must be performed* - Substrate of 3A4, so watch dosing!

Question 31

what are 3 consequences of interrupting ART

Answer 31

- rebound viremia (resistance risk) - worsening of immune function - increased morbidity and mortality

Question 32

when should ART be initiated?

Answer 32

immediately after diagnosis

Question 33

what regimen do you want to start for ART?

Answer 33

2 NRTIs + INSTI, NNRTI, or PI boosted (3 total)

Question 34

1st line initial regimen for most people with HIV: INSTI + 2 NRTIs (2 choices kinda)

Answer 34

INSTI + 2 NRTIs (Bictegravir/tenofovir alafenamide/ emtricitabine (biktarvy) OR Dolutegravir + tenofovir alafenamide or tenofovir disoproxil fumarate + emtricitabine or lamivudine

Question 35

1st line initial regimen for most people with HIV: INSTI + 1 NRTI (1 choice pretty much )

Answer 35

Dolutegravir/Lamivudine

Question 36

website for drug interactions that kleyn will almost 100% ask about

Answer 36

www.hiv-druginteractions.org

Question 37

T or F: ritonavir is a strong CYP3a4 inducer

Answer 37

false, inhibitor dumbass

Question 38

T or F: NNRTIs are CYP3A4 inducers

Answer 38

true, got you tho

Question 39

which of the following is not an UGT1A1 substrate: A. elvitegravir B. dolutegravir C. bictegravir D. Rilpivirine

Answer 39

D, only one that isnt an INSTI

Question 40

which has no interaction with 3A4? A. Maraviroc B. Fostemsavir C. Bictegravir D. Lenacapavir

Answer 40

C

Question 41

summary of drug interactions, acid reducers: - separate from po _____ by 6 hours, but never give _______ with Al or Mg.

Answer 41

INSTIs, raltegravir

Question 42

summary of drug interactions, acid reducers: - __________ and po ________ are reduced by acid reducers. - ________ is CI'd w/ PPis.

Answer 42

atazanavir, rilpivirine, rilpivirine

Question 43

summary of drug interactions, benzos: - with (class?) and (drug), preferred benzos are (3)

Answer 43

- protease inhibitors - cobicistat - loraz, oxaz, temaz (LOT)

Question 44

Summary of Drug Interactions, Corticosteroids: - With (class) and (drug), ___________ is preferred

Answer 44

- protease inhibitors - cobicistat - betamethasone

Question 45

summary of drug interactions, statins: - with (class) and (drug), low doses of (4) are preferred - with (class), dose may need increased

Answer 45

- protease inhibitors - cobicistat - ator, rosu, pita, prava - NNRTIs

Question 46

summary of drug interactions, Biguanide (metformin): - __________ increases metformin, so a dose decrease of metformin may be necessary

Answer 46

dolutegravir

Question 47

summary of drug interactions, PDE5 inhibitors: - with (class) and (drug), use very low doses q48-72 hours

Answer 47

- protease inhibitors - cobicistat

Question 48

summary of drug interactions, polyvalent cation supplements: - With (class), space apart by 6 hours - coadmin of Ca/Fe with (drug) or (drug) OK if also taken with food

Answer 48

- integrase inhibitors - dolutegravir OR bictegravir

Question 49

taking a break at resistance

Answer 49

slide 62 / handout confusing