Exam III HIV Pharm

Question 1

PathoPhys of HIV

Answer 1

Question 2

HIV 1 versus HIV 2

Answer 2

HIV = retrovirus = lentivirus

HIV - 1

• More Prevalent*
• More Pathogenic*
• HIV-1 VArients divided into groups: M, N, O, P*
• Within M (Major) group there are classes A, B, C, D, F, G, H, J, K*
• Origins Chimpanzee*

HIV - 2

• Largely limited to Western Africa*
• Less pathogenic*
• Treatment differences (HIV-2 resisitant to NNRTI’s)*
• Origins: Sooty Mangabey*

Question 3

Cell Surface receptors for HIV

Answer 3

1. CD4 Receptors

2. Chemokine Receptors

CCR5

• Found in majority of sexually transmitted HIV - 1 infection*
• Generally detectable over the entire course of infection*
• FDA-approved CCR5 inhibitor available*
• Rare delta 32 genetic mutation (immunity)*

CXCR4

Generally observed in PTs with advanced AIDS

Question 4

HIV testing

Answer 4

Seroconversion window period

Time of infection to production of antibodies

Average 3-4 weeks but up to 6 months

Acute HIV

HIV tests

Rapid (antibody tests)

• Blood or oral fluid sample (eg., in-home oral HIV test through OraQuick)*
• Faster results; require confirmation if reactive*

Combination immunoassy (‘fourth - generation test’)

• Detects HIV-1 and HIV-2 antibodies and HIV-1 protein 24 (p24) antigen*
• More sensitive in diagnosing early infection*

PCR test (polymerase chain reaction test)

Viral load tests: detect genetic material of HIV

Question 5

Antiretroviral (ART) Drug Classes

Answer 5

Nucleoside and nucleotide RT inhibitors (NRTI/NtRTI)

Generic names and in INE (eg., emtricitabine)

Non-nucleoside RT inhibitors (NNRTI)

Generic names end in virine (eg., rilpivirine)

Protease inhibitors (PI)

Generic names end in: NAVIR (eg., darunavir)

Integrase inhibitors (INSTI)

Generic names and in TEGRAVIR

Phamacokinetic boosters (for PIs and INSTIs)

Norvir (ritonavir): protease inhibitor

Tybost (cobicistat, COBI)

CCR5 inhibitor

Fusion inhibitor

Monclonal antibody (post-attachment inhibitor)

Question 6

Nucleoside and nucleotide reverse transcriptase inhibitors (NRTI)

Answer 6

Emtricitabine, FTC

Lamivudine, 3TC

Tenofovir Disoproxil Fumarate or TDF

Tenofovir alafenamide, TAF

• Better tolerated version of Tenofovir*
• Co-formulated with Emtricitabine in Descovy for HIV and HBV*
• FDA approved for HBV as Vemlidy*
• Not FDA approved for HIV as Vemlidy*

Abacavir, ABC

Question 7

Combination NRTI Products

Answer 7

Question 8

NRTI Characteristics I

Answer 8

Question 9

NRTI Characteristics II

Answer 9

Question 10

NRTI Characteristics III

Answer 10

Question 11

Non-nucleoside reverse transcriptase inhibitors (NNRTI)

Answer 11

Doravirine

Rilpivirine, RPV

Efavirenz, EFV

Question 12

Combination NNRTI Products

Answer 12

Question 13

NNRTI Characteristics

Answer 13

MoA

Inhibit RT by directly binding to it (non-competitive inhibition of RT)

Drug class side effects

Rash

• Often diffuse, slightly raised, itchy*
• Severe skin reactions reported (rare):*
• _{Toxic epidermal necrolysis (TEN)}*
• _{Steven-Johnson Syndrome (SJS)}*

Liver Toxicity

Livertox Database: https://livertox.nih.gov/

Question 14

NNRTI Drug Specific Side Effects

Answer 14

Doravirine:

N/D, abdominal pain, dizziness, HA, fatigue, Abnormal dream

Rilpivirine:

Depression, insomnia, HA, rash

Efavirenz:

CNS effects such as: dizziness, drowsiness, sleepiness, insomnia, vivid dreams

Bedtime dosing

Retrospective case reports of Neural Tube Defects in the first trimester

Question 15

NNRTI Characteristics

Answer 15

Pharmacokinetics:

Absorption/food effects:

Take with food: Rilpivirine

Take on empty stomach: Efavirenz

Metabolism

_{Liver metabolism via CYP450}

_{Substrates of CYP3A4}

_{Efavirenz is a substrate of CYP2B6 and its levels may accumulate in genetic polymorphism}

_{<em>Lower-dose Efavirenz in Symfi Lo may be better tolerated</em>}

Question 16

NNRTI Drug interactions

Answer 16

Question 17

Protease Inhibitors (PI)

Answer 17

Darunavir, DRV

_{600mg tab - dosed VID with Ritonavir (PK Booster) 100mg BID}

_{800 mg tab - dosed QD with Ritonavir (PK Booster) 100mg QD or Cobicistat 150mg QD}

Ritonavir, RTV

Atazanavir, ATV

Question 18

Combination PI products

Answer 18

Question 19

PI MoA and Class side effects

Answer 19

MoA:

_{Inhibit HIV protease}

_{Prevent cleavage of proteins, resulting in no active proteins}

Drug Class Side Effects:

_GI

_{Hyperlipidemia}

_{Possible CV risk}

_{Blood Glucose elevations}

_{Liver toxicity}

_{Possible bleeding risk in hemophiliacs}

_{Body fat re-distribution}

Question 20

PI Drug-specific side effects:

Answer 20

Possible skin reaction due to sulfonaminde:

_Darunavir

_{Fosamprenavir}

_Tipranavir

Potential Cardiovascular risk (recent study data):

_Darunavir

Hyperbilirubinemia and nephrolithiasis:

_Atazanavir

Question 21

PI Pharmacokinetics

Answer 21

Absorption/food effects:

Acid-suppressive therapy interacts with atazanavir

Metabolism:

Substrates of CYP 450 (hepatic and intestinal) and P-gp

Most PIs are also inhibitors of CYP enzymes

_{Many drug interactions (eg., statins, fluticasone, salmeterol, rifampin, Hep C antivirals, anticoagulants, certain antifungals, quetiapine, St. John’s Wort)}

_{Ritonavir: strongest metabolic inhibitor in class (CYP3A4 and 2D6)=> boosts levels of other PIs}

Question 22

Integrase Inhibitors (INSTI)

Answer 22

Raltegravir, RAL

Dolutegravir, DTG

Elvitegravir, EVG

_{Discontinued as an individual tablet}

_{Evitegravir available in combo product}

Question 23

INSTI Combinations

Answer 23

Question 24

INSTI MoA, Side Effects

Answer 24

MoA:

Inhibit integrase, prevent integration of Viral DNA into Human DNA

Drug Class side effects:

Insomnia, HA, possible weight gain, increase in liver enzymes, and creatine kinase (CK)

Drug-specific side effects:

Dolutegravir

_{Neuropsychiatric effects}

_{Neural tube defects (avoid in women of childbearing age not on contraception or within 12 weeks post conception)}

Boosted INSTI (Genvoya, Stribild)

_{N/D, renal impairment, decrease bone mineral density (renal/bone side effects: less with Genvoya)}

Question 25

INSTI Pharmacokinetics

Answer 25

**Absorption:** Elvitegravir regimens - Genvoya, Stribild: _{Take with food} **Metabolism:** All INSTIs are substrates of UGT1A1 Some are substrates of Pg-p (raltegravir) CYP3A substrates: _{Bictegravir , dolutegravir and elvitegravir regimens Elvitegravir requires PK boosting through CYP34A}

Question 26

INSTI Drug Interactions

Answer 26

Question 27

INSTI Drug Interactions II

Answer 27

Question 28

NNRTI and INSTI Combo

Answer 28

Question 29

Pharmacokinetic Boosters

Answer 29

Question 30

CCR5 Inhibitor

Answer 30

Question 31

Fusion Inhibitor

Answer 31

**_Enfuvirtide, T20_****_:_** 36-Amino acid synthetic peptide Inhibits function of transmembrane gp 41 Product has to be constituted Side effects: Injectuion site reactions \>90% Pharmacokinetics: _{Metabolism: peptide; undergoes catabolism} Drug Interactions: _{No Effect on CYP enzymes No significant Drug interactions}

Question 32

Post-Attachment inhibitor Ibalizumab

Answer 32

Question 33

Initiation of Antiretroviral Therapy (ART)

Answer 33

Question 34

HIV Treatment Guidelines: What to start?

Answer 34

Question 35

HIV Treatment Guidelines: What to start in certain clinical situations Integrase inhibitor + 2 NRTIs?

Answer 35

Question 36

HIV Treatment Guidelines: What to start in certain clinical situations NNRTI + 2 NRTIs?

Answer 36

Question 37

HIV Treatment Guidelines: What to start in certain clinical situations Boosted PI + 2 NRTIs?

Answer 37

Question 38

HIV Treatment Guidelines: What to start in certain clinical situations, cannot use abacavir, TAF, and TDF?

Answer 38

Question 39

Antiretroviral Treatments Not Recommended

Answer 39

Question 40

Characteristics of Dual NRTIs in initial ART regimens

Answer 40

Question 41

Characteristics of INSTIs in initial ART regimens

Answer 41

Question 42

Characteristics of NNRTIs in initial ART regimens

Answer 42

Question 43

Characteristics of PIs in initial ART regimens

Answer 43

Question 44

Considerations for selecting an initial ART regimen

Answer 44

Question 45

Current CDC PrEP recommendations

Answer 45

Question 46

CDC Guideline: Clinical Eligibility for PrEP

Answer 46

Question 47

CDC Guideline: REquirements before prescribing PrEP

Answer 47

Negative HIV test result within 1 week of PrEP start No signs of symptoms of acute HIV injection Normal Renal Function (eCrCl 60 mL/min or higher) No Contraindications to Emtricitabine/TDF Documented Hep B virus infection and immunization status Tests for HCV infection and link to care if needed Screen for STDs

Question 48

PT monitoring while on PrEP

Answer 48

Question 49

On-demand PrEP

Answer 49

Question 50

HIV PEP (Post-Exposure prophylaxis)

Answer 50