Flashcards in HIV drugs Deck (14)
Describe the HIV life cycle.
(1) attachment (CD4)
(2) co-receptor binding (CCR5 or CXCR4)
(3) fusion (viral gp41 / gp120)
(4) reverse transcription (RT) => Drug target
(5) integration (integrase)
(8) precursor --> proteins (protease)
What are the major HIV drug classes?
1) Nucleoside reverse transcriptase inhibitors
2) Non-nucleoside reverse transcriptase inhibitors
3) Protease inhibitors
Less widely used
4) CCR5 antagonists
5) Integrase inhibitors
6) Fusion inhibitors
How do nucleoside reverse transcriptase inhibitors work?
Block reverse transcriptase enzyme
What is a major/lethal reaction to Abacavir (a nucleoside reverse transcriptase inhibitors)?
Abacavir Hypersensitivity reaction => lethal
- Occurs in 8% of HIV patients
- Symptoms are Fever + rash +/- GI
- Seen predominantly (basically only) HLA-B*5701
- This HLA type has higher rates of autoimmune disease and slower progression to AIDS
What are other adverse drug reactions to Nucleoside Reverse transcriptase inhibitors?
1) Redistribution of fat (body habitus changes greatly)
- due to similarities in transcriptase in mitochondria
2) Mitochondrial toxicity => potentially fatal
- leads to lactic acidosis
How do Non-nucleoside reverse transcriptase inhibitors work?
Block nucleoside reverse transcriptase from an external site (i.e. like closing shut from outside)
What is the mechanism of protease inhibitors?
Blocks catalytic site by mimicking structure of peptides the protease should cleave (i.e. stops cleavage)
What is the major drug interaction of protease inhibitors?
- Watch out for CYP450 metabolized drugs
- PIs can also interfere with their own metabolism if given more than one type
What individuals are invulnerable to HIV?
Individuals without CCR5
- CCR5 antagonists have therefore become a new drug class
How do integrase inhibitors undermine integration?
They remove the portion of DNA that has been forcefully integrated into the host DNA by HIV
What are the main diseases that affect immunocompromised hosts like HIV patients and at what CD4 count?
1) Under 200 => PCP (use TMP/SMX- prophylaxis)
2) Under 100 Toxoplasma (use TMP/SMX- prophylaxis)
3) Under 50 MAC (use azithromycin- prophylaxis), CMV, crypto, Kaposi Sarcoma
What is the proper drug regimen for HIV?
Three agents from two classes => HAART (Highly active antiretroviral therapy )
What is the biggest cause of drug resistance?
Lack of drug adherence is the biggest cause of drug resistance in HIV