Exam III HIV Pharm Flashcards
Identify when not to use, ADRs and DDIs
PathoPhys of HIV
HIV 1 versus HIV 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*
Cell Surface receptors for HIV
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
HIV testing
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
Antiretroviral (ART) Drug Classes
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)
Nucleoside and nucleotide reverse transcriptase inhibitors (NRTI)
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
Combination NRTI Products
NRTI Characteristics I
NRTI Characteristics II
NRTI Characteristics III
Non-nucleoside reverse transcriptase inhibitors (NNRTI)
Doravirine
Rilpivirine, RPV
Efavirenz, EFV
Combination NNRTI Products
NNRTI Characteristics
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/
NNRTI Drug Specific Side Effects
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
NNRTI Characteristics
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>
NNRTI Drug interactions
Protease Inhibitors (PI)
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
Combination PI products
PI MoA and Class side effects
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
PI Drug-specific side effects:
Possible skin reaction due to sulfonaminde:
Darunavir
Fosamprenavir
Tipranavir
Potential Cardiovascular risk (recent study data):
Darunavir
Hyperbilirubinemia and nephrolithiasis:
Atazanavir
PI Pharmacokinetics
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
Integrase Inhibitors (INSTI)
Raltegravir, RAL
Dolutegravir, DTG
Elvitegravir, EVG
Discontinued as an individual tablet
Evitegravir available in combo product
INSTI Combinations
INSTI MoA, Side Effects
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)
INSTI Pharmacokinetics
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
INSTI Drug Interactions
INSTI Drug Interactions II
NNRTI and INSTI Combo
Pharmacokinetic Boosters
CCR5 Inhibitor
Fusion Inhibitor
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
Post-Attachment inhibitor Ibalizumab
Initiation of Antiretroviral Therapy (ART)
HIV Treatment Guidelines: What to start?
HIV Treatment Guidelines: What to start in certain clinical situations Integrase inhibitor + 2 NRTIs?
HIV Treatment Guidelines: What to start in certain clinical situations NNRTI + 2 NRTIs?
HIV Treatment Guidelines: What to start in certain clinical situations Boosted PI + 2 NRTIs?
HIV Treatment Guidelines: What to start in certain clinical situations, cannot use abacavir, TAF, and TDF?
Antiretroviral Treatments Not Recommended
Characteristics of Dual NRTIs in initial ART regimens
Characteristics of INSTIs in initial ART regimens
Characteristics of NNRTIs in initial ART regimens
Characteristics of PIs in initial ART regimens
Considerations for selecting an initial ART regimen
Current CDC PrEP recommendations
CDC Guideline: Clinical Eligibility for PrEP
CDC Guideline: REquirements before prescribing PrEP
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
PT monitoring while on PrEP
On-demand PrEP
HIV PEP (Post-Exposure prophylaxis)
