HIV: Principles and Management Flashcards
targets for types of HIV anti-retroviral drugs
reverse transcriptase (nucleoside analogue or non-nucleoside analogue)
integrase (blocked - virus cant be inserted into host cell genome)
protese (inhibition stops cleaving)
entry (fusion or CCR5 receptor inhibitor)
maturation
HIV lifecycle
- binding/attachment (HIV binds to receptors on CD4 surface)
- fusion (the HIV envelope and the CD4 cell membrane fuse
- reverse transcriptase (inside CD4, HIV releases and uses reverse transcriptase to convert its HIV RNA to HIV DNA which allows the HIV to enter the cell nucleus and combine with CD4 cell DNA)
- integration (HIV releases integrase in CD4 nucleus which is used to insert its viral DNA into the DNA of the CD4 cell)
- replication (HIV begins to use the machinery of the CD4 cell to make long chains of HIV proteins which are the building blocks of more HIV)
- Assembly (new HIV proteins and HIV RNA move to surface of CD4 cell and assemble into immature HIV)
- buding (newly formed immature HIV pushes itself out of the host CD4. the new HIV releases protease which breaks up the long protein chains in the immature virus creating the mature virus
mono vs dual vs triple therapy?
was initially mono therapy which turned out to be toxic
dual therapy then reduced mortality
triple therapy now used
what is highly active anti-retroviral therapy? (IMPORTANT)
minimum of 3 drugs from 2 drug classes (targets of HIV medication) to which the virus is susceptible
purpose of highly active anti-retroviral therapy?
reduce viral load to undetectable
restore immunocompetence
reduce morbidity and mortality
how is highly active anti-retroviral therapy delivered?
single tablet co-formulation e.g - tenofovir (NtRTI) - emtricitabine (NRTI) - efavirenz (NNTRI) one tablet once daily
important features in preventing drug resistance in HIV?
adherence mostly lifestyle tolerability pharmakokinetics drug interactions treatment interruptions (travel etc)
why is stopping drugs etc dangerous?
one of the 3 drugs lasts longer in the blood so once others wear off there will be only one left and resistance will develop
anti-retroviral therapy goals?
tolerability low toxicity low pill burden low doing frequency minimal drug interactions high barrier to resistance
side effects of HAART?
GI side effects (protease inhibitors) skin (rash, hypersensitivity, steven johnson) CNS (mood, psychosis) renal toxicity (proximal renal tubulopathies) bone (osteomalacia) CVS (MI risk, increase cholesterol) heamatology (anaemia) GI (transaminitis, fulminant hepatitis)
which types of anti-retroviral drugs are likely to cause interactions?
protease inhibitors = potent liver enzyme inhibitors
NNRTIs = potent liver enzyme inducers
some drugs require pharmacological boosting with potent liver enzyme inhibitors
liver side effects of anti-retroviral therapy?
NAFLD
Prevention medicine in HIV?
manage CVS risk factors (smoking etc) STI screening Harm reduction (manage drug use) Hep A/B vaccine flue vaccine HPV vaccine
is partner notification mandatory?
no, voluntary process can be - partner referral - provider referral - conditional referral
which partner is most likely to transmit the HIV virus?
the insertive partner
