HIV

Question 1

Differences b/w HIV 1 & 2?

Answer 1

1: More prevalent and more pathogenic
2: Less pathogenic, resistant to NNRTI’s →(Western Africia)

Question 2

What are the Cell Surface Receptors for HIV ?

Answer 2

• CD4 receptors
• Chemokine Receptors
  
  • CCR5-
    
    • dectable over entire course of infection
    • Found in majority of sexually transmitted HIV-1 infections
  • CXCR4-
    
    • Observed in pts with advanced AIDs

Question 3

What is the Seroconversion window for HIV?

Answer 3

• Time of infection to production of antibodies
  
  • average 3-4 weeks but up to 6 months

Question 4

What HIV tests do we have? What does each one do?

Answer 4

• Rapid (antibody tests)
  
  • Blood or oral fluid sample -can be done at home
    
    • Require confirmation though if test is reactive
• Combination immunoassay -4th gen. test
  
  • detects HIV-1 and HIV-2 antibodies
  • detects HIV-1 protein 24 antigen
  • More sensitive in diagnosing early infection
• PCR test
  
  • viral load tests to detect genetic material of HIV

Question 5

Nucleoside and Nucleotide reverse transcriptase inhibitors (NRTI)→ “Nuke’s”

►What drugs do we have available?

►How do we normally use these drugs?

Answer 5

Generic names end in: ine

→Except: Tenofovir, Abacavir

• Emtricitabine
• Lamivudine
  
  • Can’t combine Emtricitabine & Lamivudine because they’re structurally similar
• Tenofovir Disoproxil Fumarate (TDF)
  
  • Renal/Bone ADE’s -osteomalacia/porosis
• Tenofovir Alafenamide (TAF)
  
  • Better tolerated version of TDF – less in blood = less systemic toxicity
  • Co-formulated with emtricitabine in Descovy for HIV & HBV
• Abacavir
  
  • ABC

►How do we normally use these drugs?

→Generally: 2 NRTIs + Second class

Question 6

1. )Describe the HIV Lifecycle ? (5 steps)
2. ) How do you prevent the development of HIV resistances to the medications?

Answer 6

1. Virus identifies, binds and enters CD4+ cell
2. Fuses and transcribes into DNA
3. Integrated into nucleus
4. Replicates, exits via protease
5. Smaller pieces, gets out of cell and can infect new cells
6. Must block the virus at 2 different steps to prevent the development of resistance

Question 7

What combination NTRI products do we have available?

Answer 7

1.)

• Truvada
  
  • Emtricitabine + TDF
• Descovy
  
  • Emtricitabine + TAF
• Epizicom
  
  • Lamivudine + Abacavir

Question 8

1. What is the MOA for NRTI’s ?
2. What are the drug class side effects for NRTI’s?

Answer 8

1.)

• Inhibit HIV-1 reverse transcriptase (RT) by competitive inhibition of the enzyme, as well as chain termination
  
  • Prevents replication/integration into the cell

2.)

• Lactic acidosis
• Hepatic steatosis
• Lipodystrophy/lipoatrophy
  
  • accumulation or loss of body fat can be permamnent

Question 9

►Specific ADE’s for Emtricitabine and Abacavir and TDF and TAF?

►If baseline liver test shows hyperlipidemia consider choosing what drug?

Answer 9

• Emtricitabine
  
  • HA, GI issues, Rash
    
    • Hyperpigmentaiton of palms or soles of feet
      
      • rare-more popular in african americans
• Abacavir
  
  • Hypersensitivity rxn (severe)
    
    • ​Associtaed with HLA B*5701→ if pt. is positive for this allele then don’t give drug, rare but test can be neg and rxn can still occur
  • Increased risk of MI***
• TDF
  
  • Decreased bone mineral density- osteomalacia
  • Renal impairment- Fanconi syndrome
    
    • abnormal reabsorption of nutrients in kidneys
  • PK boosters increase risk of renal and BMD toxicity
• TAF
  
  • reduced ADE’s
    
    • ​less renal and BMD issues then TDF

►TDF associated with lower lipid levels than TAF

If baseline hyperlipidemia, consider TDF

Question 10

1. What NRTI’s have activity against Hepatitis B virus?
2. What dose adjustments do you need to make for NRTI’s?

Answer 10

1.)

• Emtricitabine
• Lamivudine
• TDF
• TAF

2.)

• Most are renally excreted → renal dose adjustements
  
  • Abacavir is excreted through the liver via ADH
    
    • Alcohol drinkers can have INCREASED levels of this drug

Question 11

What are the DDI’s with NRTI’s?

Answer 11

• Substrates of P-glycoprotein
  
  • TAF>TDF
• Do not give TAF with: →decrease TAF levels
  
  • Phenytoin, Oxcarbazepine, phenobarbital, rifampin, rifabutin, rifapentine, st. John’s wort
    
    • These are all cyp inducers

Question 12

1. What Non-nucleoside reverse transcriptase inhibitors do we have available? (NNRTI)?
2. What is their MOA?

Answer 12

• Doravirine
• Rilpivirine
• Efavirenz

2.) MOA: Inhibit reverse transcriptase by directly binding to it

→Non-competitive inhibition of reverse transcriptase

Question 13

1. What combination NNRTI products do we have available?
2. What are the side effects of NNRTI’s?

Answer 13

1.)

• Most are single tablet with 3 drug combination
  
  • 1 NNRTI + 2 NRTIs

2.)

• Rash
  
  • Toxic epidermal necrolysis
  • Steven-Johnson Syndrome
• Liver Toxicity

Question 14

What specfic ADR’s do we have for….

Doravirine?

Rilpivirine?

Efavirenz ?

Answer 14

• Doravirine→less than efavirenz and rilpivrine**
  
  • abdominal pain
  • abnormal dreams
    
    • If you dream about dora thats abnormal
• Rilpivirine -CNS side effects mainly
  
  • Depression (less than efavirenz)***
  • QTc prolongation
  • Rash
• Efavirenz - efavirenZ “Z” as in Zzzz (sleep)⇒strongest ADR’s out of the class
  
  • sleepiness
  • insomnia
  • Depression
  • vivid dreams
  • Neural tube defects in 1st trimester

Question 15

Pharmacokinetics of NNRTI’s

• Absorption/food effects of …
  
  • Rilpivirine?
  • Efavirenz?
• Metabolism of all NNRTI’s?

Answer 15

• Absorption/food effects of ?
  
  • Rilpivirine
    
    • take w/ food
  • Efavirenz
    
    • ​take w/o food
• Metabolism
  
  • Liver metabolis CYP 450-34A
  • Efavirenz-CYP2B6

Question 16

DDI’s for NNRTI’s? (3 different bullent points of DDI’s)

Answer 16

• NNRTI levels decrease with
  
  • Rifampin
  • Carbamazepine
  • Phenytoin
• Efavirenz decreases levels of
  
  • Rifampin
  • Voriconazole
  • Methadone
  • Statins
• Acid supressive therapy decrease absorption of rilpivirine and its combination products ***these drugs need to be spaced out from rilpivirine
  
  • PPI’s
  • H2-receptor antagonist
  • Antacids

Question 17

1. What Protease Inhibitors do we have available?
2. What is their MOA?

Answer 17

1.)

• Darunavir*
  
  • DOC w/n the class
• Ritonavir
• Atazanavir*

*= given with a booster (Ritonavir or Cobicistat

2.)

• MOA:
  
  • Inhibit HIV protease, preventing cleavage of proteins during replicaiton
    
    • Results in no active proteins

Question 18

1. What combination protease inhibitor products do we have available?
2. What are the class ADR’s of protease inhibitors? (six side effects)

Answer 18

1.)

• PI + booster
  
  • booster = cobicistat or ritonavir
• PI+ Booster + 2 NRTI’s

2.)

• Hyperlipidemia
  
  • esp. with older pt’s – increase dose
• possible caridovascular risk
• blood glucose elevations -caution with diabetics
• liver toxicity
• bleeding risk- caution with hemophiliacs
• body fat re-distribution (lipodystrophy)

Question 19

Drug-specific side effects of protease inhibitors….

Answer 19

• Darunavir
  
  • skin rxn’s due to sulfonamide
    
    • can still give bactrim though
  • cardiovascular risk - higher than atazanavir
• Atazanavir
  
  • hyperbilirubinemia
  • nephrolithiasis

Question 20

Aborption and Metabolism of Protease inhibitors?

Answer 20

• Absorption*******
  
  • Acid supressive therapy interacts with atazanavir
    
    • ​DOES NOT interact with Darunavir
• Metabolism
  
  • Substrates of CYP 450 and P-glycoprotein
    
    • most are also CYP 450 inhibitors-many DDI’s
  • Ritonavir -strongest metabolic inhibitor in class (b/c its a cyp booster)- boosts levels of other PI’s

Question 21

1. What drugs do we have availble for Integrase Inhibitors (INSTI)?
2. What is their MOA?

Answer 21

1.) favored as first line therapy

• Raltegravir
  
  • doesn’t have a single tablet regimen
• Dolutegravir
• Elvitegravir*
  
  • only offered in combination products

2.) MOA: blocks insertion of HIV DNA into CD4 cell DNA

Question 22

1. What combination integrase inhibitor (INSTI) products do we have available?
2. What are the general drug class side effects of INSTI?

Answer 22

• 2 NRTIs + INSTI
• 2 NRTI’s + INSTI + Booster

2.)

• Insomina
• weight gain
• increase in liver enzymes and creatine kinase

Question 23

What are the drug-specific side effects of INSTI agents…

Answer 23

• Dolutegravir
  
  • neuropsychiatric effects -caused drug to be d/c
  • neural tube defects “Dolutegravir, neural tube defect is near”
    
    • avoid in women of childbearing age not on contraception or w/n 12 weeks of post conception
  • Increased CPK (phosphokinase)
• Combination products → 2 NRTI’s + INSTI + Booster
  
  • GI issues
    
    • N/D
  • Renal impairment
  • Bone density loss

Question 24

Absorption and Metabolism of INSTI’s (integrase inhibitor)?

Answer 24

• Absorption**********
  
  • Anything with Elvitegravir in it: take with food
• Metabolism
  
  • All INSTI’s are substrates of UGT1A1
  • CYP34A substrates-everyone except RALTEGRAVIR
    
    • Bictegravir
    • Dolutegravir
    • Elevitegravir → requires PK boosting through CYP 3A4 (give with Cobicistat)
  • Some are substrates of Pg-p
    
    • Raltegravir

Question 25

DDI's of INSTI's? (4 different bullet points)

Answer 25

\*\* all interact w/ chelating agents: require spacing dose ## Footnote * Polyvalent cations: **calcium or iron supplements, cation containing antacids or laxatives** * decrease INSTI absorption * require spacing from dosing * Rifampin, Carbmazepine, Phenytoin, St, Johns wort * reduce plasma level of integrase inhibitors * Metformin * Dolutegravir increases metformin levels * Biktarvy (2 NRTI's + INSTI) * increases metformin levels * Stribild and Genvoya * similar DDI's as boosted PI's due to cobicistat

Question 26

1. What **combination product of NNRTI and INSTI** do we have? 2. Why would pt's take this product aka Indication? 3. CI's and DDI's?

Answer 26

1. Juluca (NNRTI + INSTI) 2. Indication: **Maintenance HIV therapy**→ not 1st line therapy- for **pts who have issues with NRTI's** 3. C/I with PPI's and **dofetilide (anti-arrhythmic)** 1. ​DDI's w/ anatacids and H2-antagonists

Question 27

1. What **CCR5 Inhibitor** agents do we have available? 2. What must you do prior to administering this drug? 3. What type of pt's is this drug given to? 4. ADR's?

Answer 27

1. Maraviroc 2. Patient must have expression of CCR5 inhibitor -tropic HIV 1. CCR5 tropism test must be adminstered prior to administeration 3. Indication: For experienced patients with resistance 4. ADR's: Liver toxicity - black box warning

Question 28

1. What **fusion inhibitor agent** do we have available? 2. MOA?

Answer 28

1. Agent: Enfuvirtide 2. MOA: Inhibits function of transmembrane gp 41

Question 29

1. What **Post-attachment inhibitor** agent do we have available? 2. MOA? 3. Indication?

Answer 29

1. Ibalizumab 2. MOA: binds to host CD4 cell and prevents post attachment steps ( cell to cell fusion) 3. Indication: heavily treament-experienced pts with multi drug resistance HIV-1 that is failing current regimen 1. EX: pt that is born with HIV

Question 30

1. Antiretroviral Therapy (ART) is recommended for ? 2. What test is recommended prior to starting ART?

Answer 30

1. Treatment and Prevention of HIV 2. Pregnancy test

Question 31

1. What is the intial ART regimen for most people with HIV? 2. When might you use Epzicom and Triumeq specifically?

Answer 31

1. INSTI + 2 NRTI's 2. **Epzicom and Triumeq- (both are-- INSTI + 2 NRTI's) may be used if the patient is HLA-B\*5701 negative and HIV viral load is LESS THAN 100,000 copies \*\*\* combination product must contain abacavir**

Question 32

**What Antiretroviral treatments (ART) are NOT recommended?**

Answer 32

* **Monotherapy** * **Dual NRTI regimens** * **Triple NRTI regimens** * **2-NNRTI combinations** * **2 boosters combos** * **​one booster is enough**

Question 33

If your patient is HLA-B\*5701 postive what drug should you avoid?

Answer 33

* avoid abacavir * use abacavir if VL is greater than 100,000

Question 34

1. What is the **current CDC recommended HIV prophylaxsis medication**? 2. When is it the most effective? 3. What doesn't it protect against? 4. What is the indication for this medication? 5. What are the requirements for taking this?

Answer 34

1. Truvada ( Emtricitabine/TDF) 2. Effective if taken daily 3. Doesn't protect against STD's 4. Intended in combo with other HIV prevention methods for sexually active people at substantial risk for HIV -prostitutes, druggies, homosexual sex 5. Greater than 18 years old and must weigh at least 35kg (77lbs)

Question 35

What are the CDC guidelines before prescribing Truvada? (7 bullet points)

Answer 35

* Neg HIV test * No signs or symptoms of acute HIV * Normal renal function * No C/I's to truvada * Documented Hepatitis B virus infection and immunization status * Test for HCV infection * Screen for STD's

Question 36

1. Patient monitoring while on Truvada? 2. Side effects of Truvada 3. How long can drug be taken for?

Answer 36

1. PT must be reassesed every 90 days while on med- labs, continued HIV risk, adherence, tolerability, etc. 2. Can be taken indefinitely 3. Short term- HA, abd. pain/nausea, weight loss 1. Long term- potential bone and renal side effects

Question 37

1. What steps should you take for for POST-exposure of HIV? 2. What drugs should you give?

Answer 37

1. administer antiretrovirals w/n hours of exposure for 28 days 1. optimal w/n 72 hours 2. If you were exposed in healthcare setting: (raltegravir + truvada) 1. If you were exposed in non-healthcare setting: (raltegravir + truvada OR dolutegravir + truvada)

Question 38

**What do HIV therapy do you give to pregnant women?**

Answer 38

* **Darunavir + Ritonavir -BID**