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HIV and STIs - Coggle Diagram

- - - - Erythromycin 500mg bd 14/7
  - - - Valcyclovir 500mg bd x 5/7- acute attack
      - Valcyclovir 500mg od x 1 year –suppression
      - Acyclovir 200mg five times day - pregnancy
  - - - Erythromycin 500 mg QDS 7/7
        or
        250mg QDS 14/7
      - Olfloxacin 300mgs BD 7/7
- - - - HIV has high mutation rate - genetic diversity
      - Under selective pressure from antiretoviral drugs, virus develops resistance
      - Some drugs have a lower barrier to resistance than others
    - - Entire class
        
        K103N resistance to all 1st gen NNRTIs
      - Specific drug resistance
        
        M184V - Resistance to 3TC
    - - Viral suppression
      - Multiple active agents
      - Adherence
      - Monitoring
      - Ensuring sufficient drug levels (considering pharmacokinetics and interactions)
    - - Genotype Resitance Test
      - Phenotypic Resistance Test (Testing susceptibility directly)
    - - Check for pre-existing resistant strains before initiating therapy
  - - - 2 NRTIS + 1 boosted PI / NNRTI / Integrase inhibitors
      - Modern Regimens consist of at least 3
  - - - Every 3 months
    - - GI issues
      - Lipid levels
      - Renal dysfunction
        U&E
        Urinalysis if on tenofovir
      - HbA1c
    - - Essential for assessing treatment effectiveness
    - - Adherence to medication
      - Vaccination status
      - Smoking habits
      - Partner notification
  - - - SMART trial raised concerns associated with HIV treatment
      - Abacavir
    - - Availabilty of geneics
      - Affordability of medications
  - - - Pill burden
      - Complicated regimens
      - Side effects
      - Patient factors:
        Language
        Addiction
        Depression
- - - - Side Effects
        
        Rash / allergy
        
        Bone marrow suppresion
        
        G6PD
        
        Hyperkalaemia
        
        Drug-drug interactions
  - - - Haemolytic anaemia
- - - - Enfurvitide
      - Maraviroc
    - - NRTIs Nucleoside reverse transcriptase inhibitors
        
        MOA
        
        Nucleoside analogues
        
        Structurally similar to nucleosides present in HIV RNA
        
        Compete with cellular nucleosides during viral replication
        
        Become incorporated into the genome - incoplete replication and chain termination
        
        Types
        
        Thymidine Analogues
        
        AZT - Zidovudine
        
        DDi
        
        DDC
        
        D4T
        
        Out of favour due to toxicity
        
        Non-Thymidine analogues
        
        Abacavir
        
        Lamivudine (3CT)
        
        Emtricitabine (FCT)
        
        Tenofovir
        
        Nucleotide analogy (disoproxil fumarate, alafenamide)
        
        Role
        
        Backbone of regimen
        
        Adverse Effects
        
        Mitochondrial Toxicity
        
        Varies amoung NRTIs
        
        Affects mitochondrial fx leading to degeneration
        
        Ranked ddC > ddI > d4T > 3TC > ABC > TDF > FTC
        
        Can cause lipodystrophy, dislipidemia, lactic acidosis, neuropathy, pancreatitis
        
        Bone Marrow Toxicity
        
        AZT - Zidovudine - linked to macrocytosis, anaemia, pancytopenia
        
        GI discomfort
        
        Headache
        
        Fatigue (transient)
        
        Tenovir (TDF) Issues
        
        Renal proximal tubule accumulation - kidney toxicity
        
        DNA synthesis and gene expression pertubation - bone mineral density loss :meat_on_bone:
        
        Abacavir (ABC) Issue
        
        Increased CV risk
        
        More pronounced with prolonged ART therapy
        
        Hypersensitivity
        
        Associated with HLA B5701
        
        Rash, GI, UTRI symptoms
        
        Hard to diagnose - my be fatal
        
        Interactions
        
        Renal Metabolism
        Adjust dose in renal insufficiency
      - NNRTIs Non-nucleoside reverse transcriptase inhibitors
        
        MOA
        
        Bind directly to reverse transcriptase
        
        Obstructs substrate binding site
        
        Examples
        
        Efavirenz
        
        Etravirine
        
        Rilpivirine
        
        Resistance
        
        Prone to developing resistance compared to other classes
        
        Can emerge rapidly even after single dose
        
        Pharmacokinetics
        
        Long half life
        Other agents may need continuation for a few days after discontinuation of NNRTIs
        
        Adverse Effects
        
        Crosses BBB - lipophilic
        
        Neurological
        
        Nightmares
        
        Psychiatric disturbances (often transient)
        
        Steven-Johnson rash
        
        Gynecomastia
        
        Teratogenic :spider:
        
        Interactions
        
        Metabolised by CYP450 isoenzyme 3A4
        
        Nevirapinel induces CYP450
        
        Efavirenz both induces and inhibits CYP450
    - - Ritonavir
      - MOA
        
        Inhibition of protease
        
        Leads to formation of non-infectious viral particles
        
        Impedes viral replication
      - Examples
        
        Darunavir
        
        Lopinavir
        
        Ritonavir
      - Boosted Protease Inhibitors
        
        Co-admin with low dose ritonavir inhibits CYP34A, enhacing metabolism of other PIs
        
        Increases bioavailability and penetration into HIV resevoirs
        
        Reduces dosing frequency
      - Adverse Effects
        
        GI
        
        Nausea
        
        Diarrhoea
        
        Metabolic
        
        Dislipidemias
        
        Lipodystrophy
        
        QT prolongation (Atazanavir)
        
        Hyperbilirubinaemia (Atazanavir)
        
        Drug-drug interactions - CYP3A4 metabolism
      - Interactions
        
        Metabolised by CYP450 - interactions
        
        Genetic polymorphisms can affect rate of drug metabolism
        
        Important interactions
        
        Rifampicin
        
        Azole antifungals
        
        Amiodarone - Cardiac arrhythmias due to increased plasma conc.
        
        Methadone
        
        OCP
        
        Statins
    - - MOA
        
        Blocks integration of HIV genome into host DNA
      - Examples
        
        Dolutegravir
        
        Raltegravir
        
        Elvitegravir
      - Adverse Effects
        
        Mood
        
        Sleep disturbances
        
        Neural tube defects (Dolutegravir)