HIV

Question 1

Tenofovir (TDF), Emtricitabine (FTC), Zidovudine (ZDV)

Answer 1

HIV
Nucleoside(tide) Reverse Transcriptase Inhibitors (NRTI’s)
Zidovudine (ZDV)
1. First approved antiretroviral agent
2. First-Line Therapy in Pregnant Women (Intrapartum Care)
Major Adverse Effect:
a. Myelosuppression —- macrocytic anemia
4. Also given to HIV-exposed infants!

Pre-exposure Prophylaxis
*TDF+FTC

Post-exposure Prophylaxis
*Truvada (combination form of Tenofovir 300 mg + Emtricitabine 200 mg) po once daily + *Raltegravir 400 mg po twice daily. Treat for 28 days.

MOA
• Incorporation into the viral DNA strand by HIV reverse transcriptase results in termination of the elongating DNA chain

ADE

1. Lactic acidosis/hepatic steatosis
2. Peripheral Neuropathy
3. Pancreatitis
4. Osteonecrosis, osteopenia, osteoporosis

Question 2

Non-Nucleoside(tide) Reverse Transcriptase Inhibitors (NNRTI’s)

Answer 2

HIV
Non-Nucleoside(tide) Reverse Transcriptase Inhibitors (NNRTI’s)
MOA
• Noncompetitive inhibition of reverse transcriptase (RT)
• Binds directly to RT and inhibits DNA polymerase activity by disrupting the catalytic site of the enzyme
ADE
1. Hepatotoxicity
2. Rash
3. Cardiovascular and cerebrovascular effects
C/I
• Substrates of CYP3A4, can act as inducer (NVP) or mixed inducer and inhibitor (EFV)
• ETR is substrate of 3A4, 2C9, and 2C19; inhibitor of 2C9 and 2C19

Question 3

Ritonavir

Answer 3

HIV
Protease Inhibitors
• A boosting agent to increase level of other Protease Inhibitors in Serum
MOA
• Inhibit CYP3A4 and P-glycoprotein
ADE
1. Nephropathy
2. Fat maldistribution
3. Hyperlipidemia
4. Hyperglycemia
5. Increased bleeding in hemophiliacs
Drug interactions
• All PIs are CYP3A4 substrates, and their serum levels may be affected by CYP inducers or inhibitors
• Some PIs also are inducers or inhibitors of other CYP isoenzymes or of P-glycoprotein (PGP) or other transporters

Question 4

Cobicistat

Answer 4

HIV
Protease Inhibitors
1. A boosting agent to increase level of ARV (e.g Elvitegravir) drugs in the blood. (not interchangeable with ritonavir)
- *not an ARV
MOA
• Inhibit CYP3A
ADE
1. Nephropathy
2. Fat maldistribution
3. Hyperlipidemia
4. Hyperglycemia
5. Increased bleeding in hemophiliacs
Drug Interactions
• All PIs are CYP3A4 substrates, and their serum levels may be affected by CYP inducers or inhibitors
• Some PIs also are inducers or inhibitors of other CYP isoenzymes or of P-glycoprotein (PGP) or other transporters

Question 5

Raltegravir

Answer 5

HIV
Integrase Inhibitors
MOA
• Inhibits the catalytic activity of HIV-1 integrate
• Prevents integration of linear HIV-1 DNA into the host cell genome by blocking strand transfer