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PHRM 865: Theraputics V > Lecture 26: HIV > Flashcards

Lecture 26: HIV Flashcards

1
Q

What is the target cells for the Pathophysiology for HIV?

A
  • gp120; binds to CD4 on T cells, Marcophages, Dendritic Cell
  • Primary Target = CD4 T

CD4 T helps with cell immunity and protection aganist viruses

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2
Q

What are the 3 routes of transmission for HIV?

A
  • Exposure of mucous membrane
  • Blood stream exposure
  • Mother-to-Child

ALL EXPOSED TO INFECT BODY FLUIDS

Infected Body Fluid: Blood, Semen, Pre-Cum, Rectal Fluid, Vaginal Secretions, Boob Milk
HIV NOT in urine, poop, sweat or tears

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3
Q

What are a few of the ways that there is Mucous Membrane Transmissions in HIV?

What can increase risk?

A
  • Sexual: MOST COMMON
  • Increased Risk: High viral load, STI present, Tearing, Menstruation

Others: Blood Stream Exposure and Mother-to-Child

Getting Anal > > Giving Anal > Getting Vaginal > Giving Vaginal > > BJ

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4
Q

What are is 3 stages of HIV Infections?

A
  • Stage 0: Acute Retoviral Syndrome [Fast replication]
  • Stage 1: Chronic HIV [Asymptomatic]
  • Stage 2: AIDS [Symptomatic]
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5
Q

Who should be recommended for HIV Screening?

A
  • Patients 13-64 years old [Annually for high risk]
  • ALL Pregnant women ASAP
  • ALL starting TB treatment
  • ALL going to STI clinics

TESTING SHOULD BE OPT-OUT = they have to do it

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6
Q

What is the best method of Screening Diagnostic tools for HIV?

A
  • 4th Gen Immunoassay; shows (+) or (-)
  • (+) = differentiation for HIV 1 or 2
  • (-) = stop [no HIV 1 or 2 & no pg24]
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7
Q

What is the one OTC Rapid Testing tool that is used for HIV, and what is some counseling for it?

A
  • OraQuick: uses oral fluids
  • (+) results: Should go to Dr to double check
  • (-) Results: seroconversion window [3m window to check]; Repeat Teat; Prevention
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8
Q

What are the 2 HIV Surrogate Markers?

A
  • CD4 T Lymphocyte: Primary Marker of Imunocompetence & used BEFORE therapy
  • HIV RNA PCR: Shows effectiveness of therapy & used AFTER therapy
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9
Q

When staging for HIV, what are the CD4 cells counts for each of the stages?

A
  • Stage 0: —-
  • Stage 1: > 500
  • Stage 2: 200-499
  • Stage 3 [AIDS]: < 200 or OI Diagnosis
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10
Q

What is the MOA, Class Adverse Effects and Precaution for Nucleoside Reverse Transcriptase Inhibitors for HIV Treatment?

A
  • MOA: Elongation Termination of growing proviral DNA chain [NO 3’ OH]
  • Class AE: Mitochondrial Toxicities & Lactic Acidosis [Less in “TEAL”]
  • Precaution: REQUIRES dosage adjustment [NOT Abacavir

Mito Toxic: Anemia, Granuocyotpenia, Myopathy, Neuropathy…
TEAL = Tenofovir, Emtricitabine, Abacavir, Lamivudine

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11
Q

What is the MOA, Class Adverse Effects and Precaution for Non-Nucleoside Reverse Transcriptase Inhibitors for HIV Treatment?

A
  • MOA: Binds to allosteric site of RT decreasing function
  • Class AE: Rash
  • Precautions: Caution in Hepatic issues; drug interations; high resistance [mainly nevirapine & efavirenz]
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12
Q

What is the MOA, Class Adverse Effects and Precaution for Protease Inhibitors for HIV Treatment?

A
  • MOA: Inhibits action of protease; preventing assembly, maturation, release
  • Class AE: GI issues, Insulin Resistance, Lipodystrophy
  • Precaution: NOT for Hepatic Issues; drug interactions
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13
Q

What is important to know about “Boosting” in HIV?

Main agents? What they help with?

A
  • Ritonavir & Cobicistat are potent 3A4 inhibitors
  • Increase conc. of other ARVs
  • Increases absorption, half-lifes, conc; reduces doses, frequnecy
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14
Q

What is the MOA, Class Adverse Effects and Precaution for Integrase Strand Transfer Inhibitors for HIV Treatment?

A
  • MOA: Inhibits HIV integrase, prevents viral DNA integration into host genome
  • Class AE: Weight Gain
  • Precaution: less drug interactions, gets resistance easily
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15
Q

What is the MOA and Precaution for Attachment Inhibitor for HIV Treatment?

A
  • MOA: Temsavir binds to gp120; blocking attachment to CD4
  • Precaution: Contraindicated with strong 3A4 inducer, Rarely used
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16
Q

What is the MOA and Precaution for Post-Attachment Inhibitor for HIV Treatment?

A
  • MOA: Binds to D2 on CD4 and interrupts the post-attachement requires for entry into host cell
  • Precaution: IV, NO drug interactions, Rarely Used
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17
Q

What is the MOA and Precaution for Chemokine Coreceptor (CCR5) Antagonist for HIV Treatment?

A
  • MOA: Binds to CCR5 on CD4; blocking gp120 and preventing entry
  • Precautions: Before start give tropism since its only active toward CCR5, 3A4 substrate
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18
Q

What is the MOA and Precaution for Fusion Inhibitor for HIV Treatment?

A
  • MOA: Binds to gp41 and prevents fusion and entry into CD4 cell
  • Precaution: SUBQ, No drug interactions, Rarely Used
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19
Q

What is the MOA and Precaution for Capsid Inhibitor for HIV Treatment?

A
  • MOA: Binds between p24 and interferes with many steps in viral synthesis [uptake, assembly, formation]
  • Precaution: Half-life of 8-12w, 3A4 substrate
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20
Q

What are some of the goals of therapy for HIV treament?

A
  • Suppress HIV RNA to “undectable”
  • Restore immune function
  • Reduce HIV morbidity and improve QOL
  • Prevent transmission
21
Q

What are some of the benefits of therapy for HIV treatment?

A
  • Reduces HIV mortality [reduce inflammation]
  • Reduces Transmission of HIV
  • Suppresses Viremia [decrease mutation; improve CD4 count]
22
Q

What are the common treatment therapies that are used for HIV?

A
  • Monotherapy NOT recommended for Initial
  • Two NRTIs + [INSTRI, NNSRTI, PI] is Treatment of choice
23
Q

What are the three INSTI + 2 NRTIs regimens that are used for the initial regimens for most people with HIV?

A
  • Bictegravir/Tenofovir alafenamide/Emtricitabine [Biktarvy]
  • Dolutegravir/Abacavir/Lamivudine
  • Dolutegravir + [Tenofovir Alafenamide or Disoproxil Fumarte] + [Emtricitbine or Lamivudine]

ABACAVIR needs HLA-B 5701 testing FIRST THING

24
Q

What are the one INSTI + 1 NRTIs regimens that are used for the initial regimens for most people with HIV?

A
  • Dolutegravir/Lamivudine
25
Q

What is the most common cause for treatment failure within HIV?

A
  • Poor Adherence
26
Q

What are the Positive and Negative Predictors of Adherence for HIV?

A
  • (+): Med Knowledge, Motiviation, QD Regimens…
  • (-): Neuro Issues, Substance Abuse, Unstable Housingm Concerns about AE, Poor Adherence to Clinics
27
Q

What are some of the ARV Drug Interactions Principle for HIV treatment?

A
  • PI are 3A4 Inhibitors [Ritonavir is inhibit/induce & Tipranavir is NOT]
  • NNRTIs are 3A4 Inducers [Rilpivirine & Doravine are substrates]
  • INSTIs are UGT1A1
  • Maraviroc, Fostemsavir, Lenacapavir are substrates of 3A4
  • NRTI, Ibalizumabsm, enfuvirtides have few Drug Interactions
28
Q

What is the summary of Drug Interactions fro Acid Reducers in HIV treatment?

A
  • Separate antacids from PO INSTIs by 6h
  • NEVER give raltegravir with Al or Mg
  • Atazanzvir & PO Rilpivirine are reduced
  • Rilpivirine is contraindicated with PPIs
29
Q

What is the summary of Drug Interactions fro Benzodiazepines in HIV treatment?

A
  • With Protease Inhibitors + Cobicistat; Used Lorazepam, Oxazepam, Tenazepam [LOT]
30
Q

What is the summary of Drug Interactions fro Corticosteroids in HIV treatment?

A
  • With Protease Inhibitors + Cobicistat; Beclomethasone is preferred
31
Q

What is the summary of Drug Interactions fro Statins in HIV treatment?

A
  • With Protease Inhibitors + Cobicistat; low dose of Atrovastatin, Rosuvastatin, Pitavastatin, or Pravastatin is preferred
  • With NNRTIs; increase statin dose
32
Q

What is the summary of Drug Interactions fro Biguanide in HIV treatment?

A
  • Dolutegravir increases Metformin; so decrease dose
33
Q

What is the summary of Drug Interactions fro PDE5 Inhibitors in HIV treatment?

A
  • With Protease Inhibitors + Cobicistat; use VERY low dose for 48-72 h
34
Q

What is the summary of Drug Interactions fro Polyvalent Cation Supplement in HIV treatment?

A
  • With Integrase Inhibitors; space apart by 6h
  • Contraindicated of Ca/Fe with Dolutegravir or Bictegravir
  • Take with food
35
Q

What are the type fo resistance for HIV?

A
  • Polymorphic: naturally occuring [not decrease susceptibility]
  • Major: Amino acid substitution reduce susceptibility [wipes out class]
  • Minor: Little to no effect on drug
36
Q

What are the Implications of RAMs in HIV?

A
  • Limits 1st options
  • Increase time to suppression
  • Increase the risk of failure
  • Resistance may not go away & is cumulative
37
Q

Based on the Genetic Barrier to Resistance Graph, whcih ARV medication has the highest and lowest during HIV treatment?

A
  • Boosted PiI & Dolutegravir have the highest
  • NRTIs & NNRTIs have the lowest [RT is error prone]
38
Q

For Resistance testing, what is the viral load that is needed for the best likelehood of test results for HIV Virologic Failure?

A
  • > 500 copies/mL for the best yield of resistance test

Genotype is for when you fail 1st and 2nd regimen
Phenotype for extensive history

39
Q

What are some of the causes for Virologic Failure for HIV?

A
  • Adherence [Comorbidities or to Clinic]
  • RAMs
  • Adverse Effects
  • Pill Burden
  • Drug Interactions
40
Q

What is the Preferred Regimen for ARV during pregnancy with HIV?

A
  • Dolutegravir + [Tenofovir Disoproxil Fumarate OR Tenofovir Alafenamide] + Emtricitabine OR Lamivudine]
  • Dolutegravir/Abacavir/Lamivudine [ONLY if HLA-B 5701 (-)]
41
Q

What does it mean when Undetectable = Untrasmittable in HIV?

A
  • Maintaining HIV RNA < 200 = WONT TRANSMIT
  • Could also use Condoms, PrEP, or Abstinence
42
Q

What is Pre-Exposure Prophylaxis [PrEP] in HIV Prevention?

A
  • Use of ARV in HIV (-) people that are high risk of getting HIV
  • LIFE LONG
43
Q

Who are the people at high risk for PrEP in HIV?

A
  • Condomless vaginal or anal sex
  • HIV + sex partner
  • Recent STI
  • Injection Drug use with shared needles
  • ANYONE that wants it
44
Q

What is the Oral Daily PrEP Regimen for HIV Prevention?

A
  • Emtricitabine/Tenofovir Disoproxil Fumarate 200/300mg PO QD for ALL
  • Emtricitabine/Tenofovir Alafenamide 200/25mg PO QD for men that have sex with men [not good for women]

Monitor: 1m = HIV RNA; Every 3m = HIV Ag/Ab & HIV RNA & Pregnancy Test; Every 6m = CrCl; 12m = Cholesterol & Triglyceride Level

45
Q

What is the Oral On-Demand PrEP Regimen for HIV Prevention?

A
  • Emtricitabine/Tenofovir Disoproxil Fumarate 200/300mg PO QD

2 tabs before sex; 1tab 24h after; 1 tab 48h after…

46
Q

What is the Injection PrEP Regimen for HIV Prevention?

A
  • Catoegravir 600mg IM [in butt]
  • Initial Dose –> 2nd dose 1m after 1st dose –> Every 2m after

Monitor: 1m = HIV RNA; Every 2m = HIV Ag/Ab & HIV RNA & Pregnancy Test; Every 4m = HIV RNA & STI Testing

47
Q

What is Post-Exposure Prophylaxis [PEP] in HIV Prevention?

A
  • Recommened AFTER accidental exposure [Occuptional (needlestick or fluid splash) or Non-Occuptional (sexual assault or condom break)]
48
Q

What is the PEP Regiman for HIV Prevention?

A
  • Emtrictaibine/Tenofovir disoproxil Fumarate 200/300mg PO QD + [Raltegravir 400mg PO BID OR Dolutegravir 50mg PO QD] for 28 days

PHRM 865: Theraputics V (42 decks)

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