Therapeutics ID Nelson Flashcard

HIV: Routes of Transmission

  • Sexual
  • Perinatal
  • Blood (Pareneteral, occupational exposures, blood products)

 

HIV: Life Cycle

  • Entry into human body
  • Attachment to receptors
  • Internalization (integration) of HIV virion
  • Production and release of new virions

HIV: Diagnostic Testing

1.  Antibody Tests

  • Rapid HIV Test kit
  • ELISA
  • Western Blot

2.  Antibody Window Repeat Testing

  • 6 weeks
  • 6 months
  • 1 yr

3.  Antigen Tests

  • HIV DNA PCR
  • HIV Viral Load

4.  CD4 Count

HIV Resistance Testing: Genotype

  • Tests viral genes for mutations of drug resistance
  • Takes 1-2 weeks

HIV Resistance Testing: Phenotype

  • Tests virus ability to replicate in presence of meds
  • Takes 2-3 weeks
  • Harder to interpret than genotype testing
  • More expensive than genotype testing

HIV Resistance Testing is recommended for:

  • Acute HIV infection
  • Chronic HIV infection
  • Virologic failure
  • Pregnant Patients

Indications for HIV Treatment

  • AIDS defining illness
  • HIV-associated nephropathy
  • Pregnancy
  • Coinfection Hep B Virus when HBV being treated
  • If asymptomatic , therapy is based on CD4 counts and viral titers, risks and benefits of therapy, and patient willingness to begin treatment

Risks and Benefits of Early HIV Therapy

Risks:

  • Drug adverse effects, so decreased QOL
  • Risk of drug resistance
  • Limitation of future drug options

Benefits:

  • Control easier to achieve and maintain
  • Delay immunocompromise
  • Lower risk of resistance
  • Reduction of HIV transmission

Risks and Benefits of Delayed HIV Therapy

Risks:

  • Risk of irreversible immunocompromise
  • Increased difficulty in suppressing viral replication
  • Increased risk of HIV transmission

Benefits:

  • Avoid adverse effects, so better QOL
  • Delays drug resistance
  • Preserves future drug options

Goals of HIV Therapy

  • Maximal and durable suppression of viral load
  • Restoration or preservation of immune function
  • Improvement in quality of life
  • Reduction of HIV-related morbidity and mortality

Zidovudine: Class
NRTI
Didanosine: Class
NRTI
Zalcitabine: Class
NRTI
Stavudine: Class
NRTI
Lamivudine: Class
NRTI
Abacavir: Class
NRTI
Tenofovir: Class
NRTI
Emtricitabine: Class
NRTI
Nevirapine: Class
NNRTI
Delavirdine: Class
NNRTI
Efavirenz: Class
NNRTI
Etravirine: Class
NNRTI
Saquinavir: Class
Protease Inhibitor
Indinavir: Class
Protease Inhibitor
Ritonavir: Class
Protease Inhibitor
Nelfinavir: Class
Protease Inhibitor
Amprenavir: Class
Protease Inhibitor
Lopinavir: Class
Protease Inhibitor
Atazanavir: Class
Protease Inhibitor
Fosamprenavir: Class
Protease Inhibitor
Tipranavir: Class
Protease Inhibitor
Darunavir: Class
Protease Inhibitor
Enfuvirtide: Class
Fusion Inhibitor: Binds to HIV-1 transmembrane fusion protein gp41
Maraviroc: Class
Entry Inhibitor: CCR5 co-receptor antagonist
Raltegravir: Class
Integrase Stand Transfer Inhibitor
HIV Drug Selection Principles

  • Never Monotherapy
  • Avoid Sequential Monotherapy

Initial Drug Combinations for Antiretroviral-Naive Patients

  • 2 NRTI + NNRTI
  • 2NRTI + Protease Inhibitor (boosted with Ritonavir)
  • 2NRTI + Integrase Inhibitor

Advantages and Disadvantages: 2 NRTI + NNRTI

Advantages

  • Saves Protease Inhibitor and Raltegravir for future 
  • Low pill burden
  • Less lipid SE

 

Disadvantages

  • NNRTI resistance in therapy naive patients
  • Low genetic barrier for development of resistance: Cross-Resistance among NNRTIs
  • Skin rash
  • Drug interactions

Advantages and Disadvantages: 2 NRTI + Protease Inhibitor

Advantages

  • Saves NNRTI for future
  • Higher genetic barrier for resistance
  • Protease Inhibitor resistance uncommon with failure (boosted PIs)

 

Disadvantages

  • Compromise future Protease Inhibitor regimens
  • Metabolic complications (dyslipidemia, insulin resistance, hepatotoxicity)
  • GI adverse effects
  • Drug interactions (Ritonavir, esp)
  • Higher pill burden

Advantages and Disadvantages: 2 NRTI + INSTI

Advantages

  • Saves PI and NNRTI for future
  • Fewer drug related AEs and lipid changes than Efavirenz
  • Virologic response non-inferior to Efavirenz
  • No food effect
  • Fewer drug interactions than PI or NNRTI

Disadvantages

  • Less long term experience in ART-naive 
  • Lower genetic barrier for development of resistance than boosted Protease Inhibitor
  • No data with NRTIs other than Tenofovir/Emtricitabine in ART-naive patients
  • BID dosing required

Preferred Regimens: NNRTI-Based Regimen Drug Names
Efavirenz (NNRTI)/Tenofovir (NRTI)/Emtricitabine (NRTI)

Preferred Regimens: Protease Inhibitor-Based Regimen Drug Names

  • Atazanavir (PI)/Ritonavir (PI) + Tenofovir (NRTI)/Emtricitabine (NRTI)
  • Darunavir (PI)/Ritonavir (PI) + Tenofovir (NRTI)/Emtricitabine (NRTI)

Preferred Regimen for Pregnant Women

Lopinavir (PI)/Ritonavir (PI) + Zidovudine (NRTI)/Lamivudine (NRTI)

 

BID

Preferred Regimens: INSTI-Based Regimen Drug Names

Raltegravir (INSTI) + Tenofovir (NRTI)/Emtricitabine (NRTI)
Monitoring and Goals of Therapy for HIV

  • Obtain CD4 and HIV RNA titers before starting
  • HIV RNA level < 400 after 24 weeks
  • HIV RNA level < 50 after 48 weeks
  • Persistent low-level viremia
  • Check HIV RNA titers in 2-8 weeks after initiation or after a change in antiretroviral therapy, then q 3-4 months
  • Always confirm rising titer with 2nd test
  • Check CD4 counts every 3-6 months based on HIV RNA titers

Zidovudine: Dosing for Pregnant Women who have not received ART prior to labor
2 mg/kg IV over 1 hr, then CI 1 mg/kg/hr until delivery

Zidovudine: Dosing for > 35 weeks gestational age at birth for HIV infected women who have not received ART prior to labor

 

 

  • 2 mg/kg/dose PO q6hr

OR

  • 1.5 mg/kg/dose IV q6hr

 

Infant Laboratory Monitoring

  • HIV DNA PCR
  • CBC with differential
  • Urine CMV
  • RPR

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