HIV

Question 1

HIV

Answer 1

Gp120 bind to CD4 receptors on T cells, macrophages, and dendritic cells

Primary target of HIV: CD4 helper/induce lymphocyte

Responsible for protecting against virus, intracellular bacteria, etc

Question 2

Transmission

Answer 2

Exposure to mucous membrane or damages tissue (sexual)
- receiving anal> giving anal> receiving vaginal>giving vaginal> oral

IVDU

Mother-to-child

Question 3

Stage 0: Acute retroviral syndrome (weeks)

Answer 3

Flu-like symptoms
Viral load > UL of detection (10 million copies/mL)
- creates a reservoir through seeding in lymph nodes

Question 4

Stage 1: Chronic HIV infection (years)

Answer 4

CD4 ≥ 500
Asymptomatic
Antibodies are formed but not enough to keep viral load undetected

Question 5

Stage 2: Chronic HIV infection (years)

Answer 5

CD4 200-499

Question 6

Stage 3: Acquired immunodeficiency syndrome

Answer 6

CD4 < 200 or OI
Symptomatic
OIs common

Question 7

When to start treatment

Answer 7

Recommended for all HIV-infected patients regardless of CD4
- initiate immediately (may delay 2 weeks if risk for IRIS)
- AIDS, acute infection, pregnancy
- Delay if TB meningitis or cryptococcus meningitis

Question 8

First line treatment–>3 drug regimen

Answer 8

2 NRTI + active ARV (integrase inhibitor, NNRTI, PI + enhancer)

No history of cabotegravir:
- Biktarvy (bictegravir 50 mg/emtricitabine 200 mg/tenofovir alafenamide 25 mg) QD
- Does not need any other lab tests
- Dolutegravir/tenofovir/emtricitabine or lamivudine

History of cabotegravir: PI-based regimen

OR
Dovato ( dolutegravir 50 mg + lamivudine 300 mg)
Do not give if HIV RNA > 500,000, HBV infection, ART started before results of genotype resistance

Question 9

NRTI MOA

Answer 9

Competitive inhibitor of reverse transcriptase by competing with endogenous
dATP, dCTP, dGTP, and dTTP

Higher affinity for HIV RT compared to cellular RT

Incorporates into DNA causing chain termination

MUST BE TRIPHOSPHORYLATED BY CELLULAR KINASES

Question 10

Tenofocir disoproxil fumarate

Answer 10

NRTI
Nucleotide: adenosine
Renal insufficiency and osteomalacia

Question 11

Tenofovir alafenamide

Answer 11

NRTI
Nucleotide: adenosine

Question 12

Emtricitabine

Answer 12

NRTI
Nucleotide: cytidine

Question 13

Lamivudine

Answer 13

NRTI
Nucleotide: cytidine

Question 14

Zidovudine

Answer 14

NRTI
Nucleotide: thymidine
Bone marrow suppression
Most commonly used in prenatal

Question 15

Abavacir

Answer 15

NRTI
Nucleotide: guanosine
Hypersensitivity reaction: test for HLA*B5701

Question 16

NRTI Side Effects

Answer 16

Mitochondrial toxicity: less with tenofovir, emtricitabine, abacavir, lamivudine (TEAL)

Lactic acidosis: Less with tenofovir, emtricitabine, abacavir, lamivudine (TEAL)

Renal dose adjustment: EXCEPT ABACAVIR

Question 17

NNRTI- (vir) MOA

Answer 17

Bind directly to site on reverse transcriptase at the hydrophobic pocket that alters the flexibility of the enzyme to inhibit RNA & DNA-dependent
polymerase activities

DO NOT COMPETE WITH NUCLEOTIDES–>NONCOMPETITIVE

DO NOT HAVE TO BE PHOSPHORYLATED

Question 18

Nevirapine

Answer 18

NNRTI
Dose titration over 14 days

Question 19

Efavirenz

Answer 19

NNRTI
Take on empty stomach at bedtime
CNS effects

Question 20

Etravirine

Answer 20

NNRTI
Take with food

Question 21

Rilpivirine

Answer 21

NNRTI
Take with meal

Question 22

Doravirine

Answer 22

NNRTI

Question 23

NNRTI Side Effects

Answer 23

Rash

Hepatic impairment
High levels of resistance form quickly

Question 24

Protease Inhibitors (navir) MOA

Answer 24

Inhibit the action of viral protease preventing assembly, maturation, and release of new virions

Question 25

Protease inhibitor agents

Answer 25

Atazanavir/Cobicistat -Take with food -Indirect hyperbilirubinemia Daranavir/Cobistat Fosamprenavir Lopinavir/Ritonavir Nelfinavir Ritonavir - N/V/D

Question 26

Protease inhibitor side effects

Answer 26

N/V/D Insulin resistance Lipodystrophy Hepatic impairment Drug-drug interactions

Question 27

Pharmacokinetic enhancer

Answer 27

MOA: CYP3A4 inhibitors - low doses boost the concentrations of other ART Ritonavir: anti-HIV @ doses 600 mg BID Cobicistat: no anti-HIV, increase SCr Benefits: increase absorption and systemic concentration, longer t1/2, reduce drug dose and frequency

Question 28

Integrase Strand Transfer Inhibitors (tegravir) MOA

Answer 28

Inhibits insertion of HIV DNA into the human genome Normal: 3’ processing Strand transfer-->integrase inhibitors inhibit this 3 amino acids in active site chelates both metal ions and stabilizes complex

Question 29

Raltegravir

Answer 29

INSTI CK elevations

Question 30

Elvitegravir

Answer 30

INSTI Take with food

Question 31

Dolutegravir

Answer 31

INSTI Integrase inhibitor naïve = 50 QD Integrase inhibitor experienced = 50 BID

Question 32

Bictegravir

Answer 32

INSTI

Question 33

Cabotegravir

Answer 33

INSTI

Question 34

INSTI Side effects

Answer 34

Weight gain Resistance easily to 1st generation; less resistance to 2nd generation

Question 35

Attachment inhibitor-->last line

Answer 35

MOA: Binds to Gp120 on HIV blocking attachment to CD4 T-cell receptor Fostemsavir Contraindicated with CYP3A4 inhibitors

Question 36

Post-attachment inhibitor-->last line

Answer 36

MOA: Binds to D2 of the CD4 T-cell receptor to interrupt the post attachment steps required for entry of HIV into host Ibalizumab-uiyk In-clinic IV administration

Question 37

Chemokine Coreceptor 5 antagonist

Answer 37

MOA: Binds to CCR5 cell blocking binding to Gp120 Maraviroc Before treatment, a tropism assay MUST be performed - only active against CCR5-TROPIC STRAINS of HIV - CYP3A4 substrate

Question 38

Capsid inhibitor

Answer 38

MOA: Binds to interface between p24 capsid protein - reduces uptake of proviral DNA - disrupts virus assembly and release - disrupts capsid core formation Indication: MDR who failed ART Lenacapavir SQ t1/2=8-12 weeks CYP3A4 substrate