Anti-Retrovirals Part I Flashcards
What human cells do HIV cells enter and infect?
CD4 (aka helper T cells or T4 cells) –> immune cells that orchestrate immune response
Describe how HIV enters human cells.
Binds to CD4 receptor and coreceptor to inject its viral RNA
What are the two coreceptors that HIV uses to enter human cells.
R5 and X4 –> R5 is much more common in US (99%)
Describe the steps of the HIV life cycle inside human cells after HIV RNA enters.
- Viral RNA is made into DNA via reverse transcription
- Viral DNA is integrated into the host cell DNA inside the host cell nucleus
- Virus integrated DNA make HIV pro-proteins
- The pro-proteins are cleaved and activated in the cell cytoplasm
- The activated HIV protein is packaged and departs the cell
- This departed protein restarts this process in a new healthy cell
What is the enzyme that converts viral RNA to viral DNA?
Reverse Transcriptase
What is the enzyme that allows viral DNA to enter the human cell nucleus and integrate with host DNA?
Integrase
What is a pro-protein?
A protein that must be activated
What is the enzyme that clips HIV proteins and activates them?
Protease
What causes the death of host cells in HIV?
The CD4 cell realizes it has been infiltrated and undergoes apoptosis (cell death)
Where in the HIV life cycle is the line between the window of opportunity for treatment and the point of no return?
Where viral DNA integrates with host DNA in the nucleus
After exposure to HIV, how long is the window of opportunity for effective treatment?
48 - 72 hours –> Needle sticks must be treated within this time to prevent HIV
What are the 7 points in the HIV life cycle where drugs could intervene? ID with an asterisk the points where current drugs act.
CD4 receptor * R5 coreceptor * X4 coreceptor Reverse Transcriptase * Integrase * Protease * Viral Departure
Differentiate between HIV and AIDS.
HIV becomes AIDS when CD4 is or ever has been below 200 or the patient develops a serious opportunistic infection.
What prophylaxis is given to HIV/AIDS patient with CD4 < 200 and why?
Bactrim to prevent PCP pneumonia
Why is there no cure for HIV?
Some infected CD4 cells become HIV memory cells and stay in lymph nodes for years
What class of HIV drugs are NRTIs and how do they work?
Nucleoside Reverse Transcriptase Inhibitors - drug inserts into growing DNA chain and prevents further growth.
What antivirals work similarly to NRTIs?
Acyclovir and Valacyclovir
What is the father of HIV drugs and what kind of drug is it?
AZT - Zidovudine (NRTI)
How long after the first reported HIV case in the US was the first drug introduced?
6 years (1981 - 1987)
What is the primary AE of AZT and what are the related S/S?
Anemia - tachycardia, fatigue, malaise
List two NRTIs that have almost no AEs and state how they are administered.
Lamivudine (3TC) - BID
Emtricitabine (FTC) - QD
Name an NRTI that has a high rate of causing anaphylaxis.
Abacavir
What test must be done before giving a patient Abacavir?
HLA typing test to predict risk of anaphylaxis
What is the clinical difference between Nucleotide RTIs and Nucleoside RTIs?
None - same mechanism with slightly different structure
List two nucleotide RTIs.
Tenofovir (TDF) Tenofovir Alfenamide (TAF)
Describe important clinical points about tenofovir (TDF).
Original version of the drug
Effective against Hepatitis B
Generic so low cost
Contributes to renal failure –> CrCl must be > 60 ml/hr
Describe important clinical points about tenofovir alfenamide (TAF).
New version of the drug Retains efficacy against Hepatitis B Not generic --> expensive Stays in cells where HIV replicates Less damaging to kidneys --> can use if CrCl > 30 ml/hr
What is the mechanism of action of protease inhibitors.
Prevents clipping/activation of pro-proteins by inhibiting protease enzyme
Name four protease inhibitors.
Tipranavir
Atazanavir
Ritonavir
Darunavir
Why is ritonavir not used at its full dose?
Causes too many GI AEs
How is ritonavir used currently?
In very small doses because it is the most potent CP450 inhibitor. This allows other protease inhibitors to be given less frequently.
What is the name for the method by which ritonavir is currently used?
It is used as a booster
T/F: Ritonavir has many drug interactions.
T –> because it is such a potent CP 450 inhibitor
What type of drug is Atazanavir and what drugs will it interact with and why?
Protease inhibitor that loves acid. It will interact with antacids - H2RAs (space) and PPIs (contraindicated)
What is unique about darunavir?
It has a sulfa-moiety –> do not give to patients with severe sulfa allergies
