Lecture 26: HIV Flashcards
What is the target cells for the Pathophysiology for HIV?
- gp120; binds to CD4 on T cells, Marcophages, Dendritic Cell
- Primary Target = CD4 T
CD4 T helps with cell immunity and protection aganist viruses
What are the 3 routes of transmission for HIV?
- 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
What are a few of the ways that there is Mucous Membrane Transmissions in HIV?
What can increase risk?
- 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
What are is 3 stages of HIV Infections?
- Stage 0: Acute Retoviral Syndrome [Fast replication]
- Stage 1: Chronic HIV [Asymptomatic]
- Stage 2: AIDS [Symptomatic]
Who should be recommended for HIV Screening?
- 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
What is the best method of Screening Diagnostic tools for HIV?
- 4th Gen Immunoassay; shows (+) or (-)
- (+) = differentiation for HIV 1 or 2
- (-) = stop [no HIV 1 or 2 & no pg24]
What is the one OTC Rapid Testing tool that is used for HIV, and what is some counseling for it?
- OraQuick: uses oral fluids
- (+) results: Should go to Dr to double check
- (-) Results: seroconversion window [3m window to check]; Repeat Teat; Prevention
What are the 2 HIV Surrogate Markers?
- CD4 T Lymphocyte: Primary Marker of Imunocompetence & used BEFORE therapy
- HIV RNA PCR: Shows effectiveness of therapy & used AFTER therapy
When staging for HIV, what are the CD4 cells counts for each of the stages?
- Stage 0: —-
- Stage 1: > 500
- Stage 2: 200-499
- Stage 3 [AIDS]: < 200 or OI Diagnosis
What is the MOA, Class Adverse Effects and Precaution for Nucleoside Reverse Transcriptase Inhibitors for HIV Treatment?
- 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
What is the MOA, Class Adverse Effects and Precaution for Non-Nucleoside Reverse Transcriptase Inhibitors for HIV Treatment?
- MOA: Binds to allosteric site of RT decreasing function
- Class AE: Rash
- Precautions: Caution in Hepatic issues; drug interations; high resistance [mainly nevirapine & efavirenz]
What is the MOA, Class Adverse Effects and Precaution for Protease Inhibitors for HIV Treatment?
- MOA: Inhibits action of protease; preventing assembly, maturation, release
- Class AE: GI issues, Insulin Resistance, Lipodystrophy
- Precaution: NOT for Hepatic Issues; drug interactions
What is important to know about “Boosting” in HIV?
Main agents? What they help with?
- Ritonavir & Cobicistat are potent 3A4 inhibitors
- Increase conc. of other ARVs
- Increases absorption, half-lifes, conc; reduces doses, frequnecy
What is the MOA, Class Adverse Effects and Precaution for Integrase Strand Transfer Inhibitors for HIV Treatment?
- MOA: Inhibits HIV integrase, prevents viral DNA integration into host genome
- Class AE: Weight Gain
- Precaution: less drug interactions, gets resistance easily
What is the MOA and Precaution for Attachment Inhibitor for HIV Treatment?
- MOA: Temsavir binds to gp120; blocking attachment to CD4
- Precaution: Contraindicated with strong 3A4 inducer, Rarely used
What is the MOA and Precaution for Post-Attachment Inhibitor for HIV Treatment?
- MOA: Binds to D2 on CD4 and interrupts the post-attachement requires for entry into host cell
- Precaution: IV, NO drug interactions, Rarely Used
What is the MOA and Precaution for Chemokine Coreceptor (CCR5) Antagonist for HIV Treatment?
- MOA: Binds to CCR5 on CD4; blocking gp120 and preventing entry
- Precautions: Before start give tropism since its only active toward CCR5, 3A4 substrate
What is the MOA and Precaution for Fusion Inhibitor for HIV Treatment?
- MOA: Binds to gp41 and prevents fusion and entry into CD4 cell
- Precaution: SUBQ, No drug interactions, Rarely Used
What is the MOA and Precaution for Capsid Inhibitor for HIV Treatment?
- MOA: Binds between p24 and interferes with many steps in viral synthesis [uptake, assembly, formation]
- Precaution: Half-life of 8-12w, 3A4 substrate
What are some of the goals of therapy for HIV treament?
- Suppress HIV RNA to “undectable”
- Restore immune function
- Reduce HIV morbidity and improve QOL
- Prevent transmission
What are some of the benefits of therapy for HIV treatment?
- Reduces HIV mortality [reduce inflammation]
- Reduces Transmission of HIV
- Suppresses Viremia [decrease mutation; improve CD4 count]
What are the common treatment therapies that are used for HIV?
- Monotherapy NOT recommended for Initial
- Two NRTIs + [INSTRI, NNSRTI, PI] is Treatment of choice
What are the three INSTI + 2 NRTIs regimens that are used for the initial regimens for most people with HIV?
- 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
What are the one INSTI + 1 NRTIs regimens that are used for the initial regimens for most people with HIV?
- Dolutegravir/Lamivudine
What is the most common cause for treatment failure within HIV?
- Poor Adherence
What are the Positive and Negative Predictors of Adherence for HIV?
- (+): Med Knowledge, Motiviation, QD Regimens…
- (-): Neuro Issues, Substance Abuse, Unstable Housingm Concerns about AE, Poor Adherence to Clinics
What are some of the ARV Drug Interactions Principle for HIV treatment?
- 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
What is the summary of Drug Interactions fro Acid Reducers in HIV treatment?
- Separate antacids from PO INSTIs by 6h
- NEVER give raltegravir with Al or Mg
- Atazanzvir & PO Rilpivirine are reduced
- Rilpivirine is contraindicated with PPIs
What is the summary of Drug Interactions fro Benzodiazepines in HIV treatment?
- With Protease Inhibitors + Cobicistat; Used Lorazepam, Oxazepam, Tenazepam [LOT]
What is the summary of Drug Interactions fro Corticosteroids in HIV treatment?
- With Protease Inhibitors + Cobicistat; Beclomethasone is preferred
What is the summary of Drug Interactions fro Statins in HIV treatment?
- With Protease Inhibitors + Cobicistat; low dose of Atrovastatin, Rosuvastatin, Pitavastatin, or Pravastatin is preferred
- With NNRTIs; increase statin dose
What is the summary of Drug Interactions fro Biguanide in HIV treatment?
- Dolutegravir increases Metformin; so decrease dose
What is the summary of Drug Interactions fro PDE5 Inhibitors in HIV treatment?
- With Protease Inhibitors + Cobicistat; use VERY low dose for 48-72 h
What is the summary of Drug Interactions fro Polyvalent Cation Supplement in HIV treatment?
- With Integrase Inhibitors; space apart by 6h
- Contraindicated of Ca/Fe with Dolutegravir or Bictegravir
- Take with food
What are the type fo resistance for HIV?
- Polymorphic: naturally occuring [not decrease susceptibility]
- Major: Amino acid substitution reduce susceptibility [wipes out class]
- Minor: Little to no effect on drug
What are the Implications of RAMs in HIV?
- Limits 1st options
- Increase time to suppression
- Increase the risk of failure
- Resistance may not go away & is cumulative
Based on the Genetic Barrier to Resistance Graph, whcih ARV medication has the highest and lowest during HIV treatment?
- Boosted PiI & Dolutegravir have the highest
- NRTIs & NNRTIs have the lowest [RT is error prone]
For Resistance testing, what is the viral load that is needed for the best likelehood of test results for HIV Virologic Failure?
- > 500 copies/mL for the best yield of resistance test
Genotype is for when you fail 1st and 2nd regimen
Phenotype for extensive history
What are some of the causes for Virologic Failure for HIV?
- Adherence [Comorbidities or to Clinic]
- RAMs
- Adverse Effects
- Pill Burden
- Drug Interactions
What is the Preferred Regimen for ARV during pregnancy with HIV?
- Dolutegravir + [Tenofovir Disoproxil Fumarate OR Tenofovir Alafenamide] + Emtricitabine OR Lamivudine]
- Dolutegravir/Abacavir/Lamivudine [ONLY if HLA-B 5701 (-)]
What does it mean when Undetectable = Untrasmittable in HIV?
- Maintaining HIV RNA < 200 = WONT TRANSMIT
- Could also use Condoms, PrEP, or Abstinence
What is Pre-Exposure Prophylaxis [PrEP] in HIV Prevention?
- Use of ARV in HIV (-) people that are high risk of getting HIV
- LIFE LONG
Who are the people at high risk for PrEP in HIV?
- Condomless vaginal or anal sex
- HIV + sex partner
- Recent STI
- Injection Drug use with shared needles
- ANYONE that wants it
What is the Oral Daily PrEP Regimen for HIV Prevention?
- 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
What is the Oral On-Demand PrEP Regimen for HIV Prevention?
- Emtricitabine/Tenofovir Disoproxil Fumarate 200/300mg PO QD
2 tabs before sex; 1tab 24h after; 1 tab 48h after…
What is the Injection PrEP Regimen for HIV Prevention?
- 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
What is Post-Exposure Prophylaxis [PEP] in HIV Prevention?
- Recommened AFTER accidental exposure [Occuptional (needlestick or fluid splash) or Non-Occuptional (sexual assault or condom break)]
What is the PEP Regiman for HIV Prevention?
- Emtrictaibine/Tenofovir disoproxil Fumarate 200/300mg PO QD + [Raltegravir 400mg PO BID OR Dolutegravir 50mg PO QD] for 28 days
