HIV Drugs

Question 1

What’s the goal of therapy in HIV?

Answer 1

maximally inhibit viral replication and reduce viral RNA to undetectable levels

Question 2

After therapy is initiated, an increase in viral load may indicate what?

Answer 2

drug resistance

Question 3

What’s the general strategy in terms of drug combo in adults who have never been treated for HIV before?

Answer 3

one of these: NNRTI, protease inhibitor, or integrase inhibitor
plus a dual combo of NRTIs

Question 4

What are the four nucleoside reverse transcriptase inhibitors we know?

Answer 4

zidovudine (AZT)
lamivudine
emtricitabine
abacavir

Question 5

What’s the mechanism of the NRTIs?

Answer 5

they competitively inhibit reverse transcritase and can be incoporated into viral DNA chain and cause termination

Question 6

What do the NRTIs need in order to become active?

Answer 6

they need to be phosphorylated by cellular enzymes to the trphosphate form in order to be active

Question 7

What are the general adverse affects of the NRTIs?

Answer 7

you can get a potentially fatal syndrome of lactic acidosis with hepatis steatosis
this is likely due to mitochodnrial toxicity

they’re also associated with fat redistribution and thus, hyperlipidemia

Question 8

What are th emore specific side effects for zidovudine?

Answer 8

granulocytopenia and anemia - in up to 45% of patient!
also CNS disturbances: severe headache, insomnia, malaise
nausea

Question 9

What’s the specific side effect for abacavir?

Answer 9

hypersensitivity reactions

Question 10

What’s the one NUCLEOTIDE reverse transcriptase inhibitor

Answer 10

tenofovir

Question 11

What’s the mechanism of action for tenofovir?

Answer 11

same as the nucleosides - chain terminator

Question 12

What’s the adverse effects of tenofovir?

Answer 12

nausea, vomiting, diarrhea and potential for renal failure

fatal lactic acidosis has been reported

Question 13

WHat are the two non nucleoside reverse transcriptase inhibitors?

Answer 13

efavirenz and etravirine

Question 14

What’s the mechanism for efavirenz and etravirine?

Answer 14

they bind directly to the reverse transcriptase enzyme at a distinct side and render it unable to produce viral DNA

Question 15

True or false: the non nucleoside reverse transcriptase inhibitors do not require phosphorylation like the nucleoside RT inhibitors do.

Answer 15

true

Question 16

Are the NNRTIs more effective against HIV1 or 2?

Answer 16

HIV-1

Question 17

What are the general adverse effects of the NNRTIs?

Answer 17

severe rashes

metabolized by cyp450 - drug interactions

Question 18

Which NNRTI has the specific side effect of vivid dreams, nightmares and hallucinations?

Answer 18

efavirenz

Question 19

What are the more specific side effects for etravirine?

Answer 19

rash, nausea, peripheral neuropathy

Question 20

What are the three protease inhibitors?

Answer 20

atazanavir
ritonavir
darunavir

Question 21

What’s the mechanism of the protease inhibitors?

Answer 21

they ihibit protease, so the pre-proteins don’t get cleaves to the necessary proteins for the virus
this means the virus is no longer infectious because new viral particles cannot mature

Question 22

What are the adverse effects of the protease inhibitors?

Answer 22

GI disturbances
hepatotoxicity
hyperglycemia
insulin resistance
hyperlipidemia
peripheral lipoatrophy and central fat accumulation
metabolized by/inhibit CYP3A4

Question 23

Which protease inhibitor is poorly tolerated at high doses, so it’s given to increase the serum concentrations of other protease inhibitors, thus decreaseing their dosage frequency?

Answer 23

ritonavir

Question 24

HOW does ritonavir increase the serum concentrations of the other protease inhibitors?

Answer 24

it’s a potent inhibitor of CYP3a4, which metabolizes the other proteases to decrease their effectiveness

Question 25

What drug is the fusion inhibitor

Answer 25

enfuvirtide

Question 26

How does efuvirtide work?

Answer 26

It binds to gp41 and prevents the conformational change necessary for HIV to fuse with the host cell membrane

Question 27

How is efuvirtide administered?

Answer 27

subQ bid

Question 28

What are the adverse effects of efuvirtide? What infection does it increase the risk for?

Answer 28

you have high incidence of local reactions - pain, erythema, induration, nodules, cysts

higher incidence of bacterial pneumonia

Question 29

Why is efuvirtide such a great drug to have in our aresenal?

Answer 29

it works against HIV that is resistant to all other classes of antiretrovirals

Question 30

What’s the integrase inhibitor?

Answer 30

raltegravir

Question 31

How does raltegravir work?

Answer 31

It inhibits integrase, so you don’t get the DNA strand transfer necessary for provirus integration

Question 32

WHat drug acts as a CCR5 antagonist?

Answer 32

maraviroc

Question 33

What are the common side effects of maraviroc?

Answer 33

pyrexia, rash, postural dizziness

Question 34

What term do we use for combo therapy with two RTIs and a PI?

Answer 34

highly active antiretroviral therapy = HAART

Question 35

Long term use of HAART is associated with what adverse secodnary effect?

Answer 35

lipodystropy

Question 36

What happens in lipodystorphy?

Answer 36

you get wasting of subcutaneous fat with central adiposity

leads to HL, insulin resistance and DM