Drug Treatment for HIV Flashcards
what are the principles of viral Treatment?
any stage of virus replication cna be a target for a drug
drug must be more toxic to virus than host
chemotherapeutic indec= macimum tolderbale dose per kg of weight weight. minimum dose per Kh body weight that will cure disease
hight ther CI the better- more specific to the virus wont attack cellular functions
what factprs may increase viral drugs resistance?
high virla replciation (RNA> DNa viruses)
adherence to medication
effectiveness of drug
mutations in virus that leads to replciation
Describe the structure of HIV
viral surface proteins- GP120 and GP41
viral prtoeins inside viurs- Protease, reverse transciptas, integrase
viral RNA genome
capsid
describe number of pills taken in hiv medication today?
most people will be on a single tablet regime- improves compliance
desccribe the mechanims of action of NRTI (nucloeisde revere transcriptase inhibitors)
block viral RNA being converted to ds viral DNA- blocks Revers trancirptase
NRTI- look like nucelotides , mistaken for nucleotides by RT- stops DNa chain growing
AZT- Zidovudine (ZDV) is a thymidine analogue
what are the side effects of NRTIs
inhibits mitochondiral replication
potent inhbitors of DNA polymerase essential for mitochondiral replication
lactic acidosis
steatosis (fatty liver)
lipoatrophy- loss of fat especiall in face- obivious phenotype
metaboli syndrome (central obesity and buffalo hump
More modern NRTIs don not blokc DNA polymeras need for essential Mitochondiral replication
Describe the mechainsm of Resistacne to NRTI
nucleosidsd eanalogues removed by mutaten RT by cleave process- pyrophopshorylase PPI, recognises that translcoation si blocked an analogue is removed
this happens readily- msot NRTI have a low genetic barrier for reisstnce-
must use in combiantion with other drugs
(AZT always used in combinatio )
what type of drug is Zidovudine
AZT- thymidie analgoue- NRTI
Describe the mechanims of Action of NNRTI (non nucloside Reverse trnacriptase inhbitors)
NNRTIS bind directly to RT
stop ability of RT to ass new nucleotide to the growing DNa chian
highyl effective- however single point mutation un viru can block
Describe the mechanism of action of Protease inhibotrs
Protease is an enzyme that cleaves the viral poly protein- if cleavge does not occur the virus cannot mature so is not infectious
Protease inhbitors block the action of the proteases
resistnac eis through conformational changes in the protease
what is DRV (darunavir) and how does it overcome drug resistance HIV
bidns to 12 didfferent places on the protease enzyme
Protease inhbitor
Describe the mechanism of action of funsion inhbitor- T20, why is it not regularly used
prevents fusion of HIV virus to CD4 cells- preventing hair pining of the GP41 molecules- oprevent effacement of HIV virion and CD4 cell
needs regular injection- so not readily used
what are CCR5 inhbitors, when does resisatnce occur
fusion inhbitors
reisstnc eoccurs when CCR5 tropic virus (requires CCR5) as its corecpeotr
switches to CXCR4 tropism
Describe the mechanism of action of Integrase inhbitors
hugely effective drugs
bind integrase prevent integration of viral DNa into genome- lwo side efefcts]
prevent integration fo virla DNa into the human genome
What are the principles of HIV anti-retroviral therapy
HAART- highyl active antiretroviral therpay
- choice depnds on the patient situation
- most commonyl dual NRTI and single NNRTI
- cheep and still highly affective
