HIV Antivirals

Question 1

Non-nucleoside / nucleotide RTI’s

Answer 1

Abacavir
Tenofovir
Lamivudine/Emtricitibine
Efavirenz

Question 2

HIV protease inhibitors

Answer 2

Ritonavir
Darunavir
Atazanavir

Question 3

Fusion, Entry, and Integration Inhibitors

Answer 3

Enfuvirtide
Maraviroc
Dolutegravir

Question 4

General mechanism of resistance in retroviruses

Answer 4

Lack proofreading - lots of mutations - some of the mutations lead to resistance

Question 5

Zidovudine/AZT general mechanism

Answer 5

Acts as a nucleoside, Competitive inhibition of RT, integration into viral DNA.

Question 6

NRTI toxicity

Answer 6

Interact with mitochondrial DNA polymerase (more similar to viral than most human DNA polymerases) - Mitochondrial toxicity - can lead to lactic acidosis with hepatic steatosis - life threatening.

Question 7

Abacavir Mechanism

Answer 7

Guanosine Analog, inhibits reverse transcriptase

Question 8

Abacavir ADME

Answer 8

PO, Rapid, extensive absorbtion, M -Hepatic, E- Renal

Question 9

Abacavir Toxicities

Answer 9

MI - caution in CV desease, Hypersensitivity - can be fatal. CI in HLA-B*5701 mutation.
Skin Rash 50%

Question 10

Lamivudine/ Emtricitabine mechanism

Answer 10

Cytosine Analog - Inhibits RT. Used in HBV treatment too.

Question 11

Lamivudine/ Emtricitabine ADME

Answer 11

Administered with Tenofovir, Rapid absorbtion, 1/3 protein bound, 5% metabolized, Renal Excretion

Question 12

Lamivudine/ Emtricitabine toxicities

Answer 12

Not recommended for concurrent admin with lamivudine. Otherwise same as other NRTI’s

Question 13

NUCLEOTIDE reverse transcriptase inhibitor

Answer 13

Tenofovir

Question 14

Tenofovir mechanism

Answer 14

Acyclic nucleotide analog of adenosine - ONLY NUCLEOTIDE RTI - Terminates chain after incorporation into DNA.

Question 15

Tenofovir ADME

Answer 15

administered with emtricitabine - 1st line. Renal excretion.

Question 16

Tenofovir toxicity

Answer 16

Fatigue, weakness, RENAL ACCUMULATION - tubular necrosis, renal failure, fanconin’s syndrome.

Question 17

Non- Nucleotide RT Inhibitor (NNRTI)

Answer 17

Efavirenz

Question 18

Efavirenz ADME

Answer 18

Extensive hepatic metabolism - CYP3A4 inhibition - DDI’s - limits use in HAART

Question 19

Efavirenz toxicity

Answer 19

Nightmares / psychiatric disturbances - resolves on its own.

Question 20

Protease inhibitors general mechanism

Answer 20

Prevents release of viral core proteins and maturation of virus particles.

Question 21

Ritonavir - DDI’s

Answer 21

Inhibits CYP3A4 - use this to slow down metabolism of other drugs - “Boosting”

Question 22

Ritonavir toxicities

Answer 22

Increased LFT’s, triglycerides / LDL

Question 23

Treatment of choice for treatment naive patients

Answer 23

Ritonavir / Atazanavir

or

Ritonavir / Darunavir

Question 24

Atazanavir toxicities

Answer 24

hyperbilirubinemia, rash, kidney stones, gallstones, PR prolongation, decreased absorbtion if used with PPI’s

Question 25

Darunavir toxicities

Answer 25

Rash, can have cross reaction with sulfa drugs.

Question 26

Lopinavir - important stuff

Answer 26

Only available in a fixed does combo with ritonavir, which raises its blood level. OK IN PREGNANCY.

Question 27

Maraviroc - Mechanism

Answer 27

Entry inhibititor - Selectively binds to CCR5, which is a receptor on CD4+ cells HIV needs to get inside.

Question 28

Maraviroc use

Answer 28

Resistant HIV -1

Question 29

Maraviroc toxicity

Answer 29

hepatotoxic

Question 30

Enfuvirtide mechanism

Answer 30

Binds to gp41 - part of the VIRUS, prevents fusion and entry.

Question 31

Enfuvirtide Use

Answer 31

HIV-1 only, treatment experienced patients with ongoing viral replication. Use combo therapy because resistance can develop.

Question 32

Dolutegravir mechanism

Answer 32

Integrase strand transferinhibitor - binds integrase and interferes with replication and integration of virus into host genome.

Question 33

Dolutegravir toxicity

Answer 33

Hypersensitivity, elevated LFT’s, generally well-tolerated