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HIV - Coggle Diagram

- - - - Comes in TDF (older) and TAF (newer) where TAF has better absorption into cell nucleus reducing organ toxicities and lowers the dose required.
      - Used for backbone therapy - can cause nephrotoxicity, fracture risk and GI disturbance (reduced when taking with food), care in renal impairment. These kidney ADRs are less with TAF
    - - Analogue incorporated into DNA but different structure causing DNA chain termination
      - Use for backbone therapy - minimal toxicities, hyperpigmentation may occur and careful in renal impairment
    - - Well tolerated, potential hair loss and insomnia, care in renal impairment
    - - First gen ART - hard to tolerate and felt worse + resistance occured
    - - Hypersensitivty risk in HLA*5071 causing fever and rash, potential increase risk in MI in older patients. Liver metabolised (3A4) thus potential DDIs.
    - - Delays progession to AIDS/Mortality, decrease HIV related morbidities (Nephropathy, CVD risk, Malignancy and Neurology (aids dementia)) and prevention of transmission.
      - ARTs recommended for everyone with HIV infection and to prevent transmission, but initiation of ART is made by individuals.
  - - - Most virologically active, once daily dosing on empty stomach.
      - Potential neuropsychiatric effects - sleep distrubance, abnormal dreams, fatigue, depression and suicidal ideation. (Subsides winthin a month)
      - CYP3A4 inducer and inhibitor - mostly induction but dose changes are not required for this drug, but other substrates may require dose changes.
    - - (Evipleria replacement for Atripla), fewer CNS, dyslipidaemia and skin rash. Was a good option until INSTIs were developed. Slightly better than Efavirenz due to less ADRs
      - Potential 3A4 DDIs (its a 3A4 substrate), less effective at high viral loads, must take with fatty meal to increase absorption and requires a low pH for effective absorption.
    - - Used for resistance to nNRTIs and other classes unavailable due to its flexible conformation. 2nd line on PBS, twice daily after food and generally well tolerated. 80% excreted in faeces thus minimal hepatic and kidney interactions.
    - - Very effective and powerful, good PK and once daily dosing. Renally cleared thus less DDIs with CYP enzymes, no food interaction and generally well tolerated
    - - Hep B cross activity - can also inhibit Hep B in some effect, thus changing therapy may influence an imbalance of supression causing loss of control in either one of the viruses.
      - Can inhibit human mitochondrial DNA polymerase - cause lactic acidosis, peripheral neuropathy and fat loss and panacreatitis
      - Greatest level of potential mutation and resistance. Hepatic metabolism, complex PK (auto-induction, long hlaf lives and PGP substrates.
  - - - Same efficacy as COBI and RTV. better PK and ADR profile, but does have GI disturbance, hepatitis, neutropenia are common, skin rash and SJS are rare.
      - Blocks OCT2 active kidney transport.
    - - Can be used in 2 dosing strengths. 1200mg to kill virus or 200mg as a PK booster. 200mg dose has low ADRs and well tolerated.
      - Blocks MATE1 active kidney transport.
    - - Pure PK booster with strong inhibition of 3A4, great aqueous ability and improved side effects profile with reduced adipose and insulin resistance effects. No HIV activity thus no resistance potential.
      - Blocks MATE1 active kidney transport.
  - - - No food requirements and 3A4 DDIs which is good for polypharmacy, very tolerable and twice daily dosing. STR is a triple therapy, still preferred over Atripla (dual therapy) due to good ADR profile.
      - Resistance increasingly observed, more data in STR with tenofovir and emtricitabine.
    - - Quad pill therapy as Genova (TAF + Emtricitabine + Cobicistat + Elvitegravir). highly effective and well tolerated.
      - EVG is metabolised by 3A4 thus potential DDIs similarly to PIs.
    - - Used in STR as Triumeq (Abacavir + Lamivudine + Dolutegravir), highly effective and well tolerated. DTG has the highest barrier to resistance
      - In combo abacavir - risk of MI, and DTG has significant weight gain, potential increase in all CVD risk. Blocks OCT2 but stabilises in 4 weeks.
    - - Excellent INSTI, comes in STR as Biktarvy (TAF + Emitricitabine + Bictegravir). Best backbone + INSTI = highly effective and no boosting.
      - Does interact with cations, contraindicated if GFR < 30 and safety is not recommended in first trimester.
  - - - Fusion inhibitor - synthetic AA analogue binds to gp41 preventing infection. Twice daily subcut dosing and expensive
      - Local irritation and risk of bacterial pneumonia
    - - CCR5 antagonist, twice daily dosing adn only effective on R5 tropic.
      - Hepatotoxicity, increased CV risk, 3A4 substrate and care with renal impairment <50mL/min