Anti-Retroviral Agents

Question 1

What are the two goals of HIV treatment (he lists 4).

Answer 1

1. Achieve durable virologic suppression
2. Stabilize or restore immune function
3. Maintain or improve patient’s QOL
4. Reduce HIV related mobidity and mortality

Question 2

How do Nucleoside Reverse Transcriptase Inhibitors (NRTIs) reduce viral multiplying?

Answer 2

Target viral replication only in early stages of HIV infection:
-incorporates “false” nucleosides that lack a 3’-hydroxyl group. This functional group is required for elongation of a DNA strand during synthesis, without it, synthesis stops

Question 3

How do Non-nucleoside Reverse Transcriptase Inhibitors (NNRTIs) function?

Answer 3

The drugs bind to an allosteric site (different from the active site) of the enzyme. This binding changes the conformation of the RT enzyme and inhibits its function. Only works in the early stages of the infection.

Question 4

Why is viral protease important for an HIV infection and how do Protease Inhibitors (PIs) affect this enzyme?

Answer 4

Viral protease cuts the final HIV protein that is synthesized in transcription into the essential viral enzymes (RT, protease, integrase) so they can be packaged into new viruses. PIs bind to the active site of the enzyme to inhibit it.

Question 5

MOA and indication for Enfuvirtide

Answer 5

MOA: viral fusion inhibitor (blocks gp41)
Indication: advated HIV infection that does not respond to normal anti-retroviral therapy

Question 6

What kinds of drugs are used in PI based HAART?

Answer 6

1 PI + 2 NRTIs

ex. lopinavir/ritonavir + zidovudine or stavudine + lamivudine

Question 7

What is an advantage of using an NNRTI based HAART over a PI based regimen?

Answer 7

PIs often cause dyslipidemias, NNRTIs do not.

The only drawback is NNRTIs are not as potent as PIs

Question 8

Name the two tests that monitor and determine the severity of an HIV infection.

Answer 8

1. Plasma HIV RNA levels

2. CD4 T cell count

Question 9

Name the adverse reactions of the NRTIs:

1. Zidovudine
2. Stavudine
3. Didanosine

Answer 9

1. Bone Marrow Suppression
2. Peripheral Neuropathy
3. Peripheral Neuropathy (major), pancreatitis (minor)

Question 10

Name two signs that the antiretroviral therapy has failed.

Answer 10

1. Inadequate viral suppression

2. Unsatisfactory increase in CD4 T cells

Question 11

Name an adverse reaction of PIs and NNRTIs.

Answer 11

Hypersensitivity reactions

Question 12

Which enzyme metabolizes PIs?

Answer 12

CYP3A4

Question 13

Which 2 NRTIs are the preferred agents for HIV management?

Answer 13

1. Emtricitabine

2. Tenofovir

Question 14

Name the population that should not receive the drug efavirenz.

Answer 14

Pregnant patients