Anti-retroviral agents

Question 1

ends in “navir”

Answer 1

protease inhibitors which cleave the unnecessary bits to allow for folding into compact infectious HIV particle shape; class side effects = GI upset.

Metabolized in the liver by CytP450 and specifically 3A4 which they inhibit - thus, if given with other CytP450/3A4 inhibitors, can cause reduced clearance and drug-drug interactions.

Resistance slow to develop bc multiple mutations required.

Question 2

middle “tegr”

Answer 2

integrase strand transfer inhibitors - inhibit the insertion of HIV-1 DNA into host genome. Circular non-integrated episomes form instead which are noninfectious.

Best tolerated class with fewest side effects due to liver metabolism by glucurodination instead of CytP450.

Resistance slow to develop because multiple mutations required.

Question 3

maraviroc

Answer 3

CCR5 inhibitor, blocks HIV entry into cells. Requires viral tropism testing prior to initiation. Resistance slow to develop. Main side effect = URI.

Question 4

enfuvirtide

Answer 4

fusion inhibitor that blocks conformational change in gp41 that is required for fusion; multiple mutations required for resistance thus resistance is slow to develop - good for MDR HIV.

Question 5

“vir” in the middle

Answer 5

Non-nucleoside reverse transcriptase inhibitors (NNRTIs) > local pH change or steric hindrance causes inhibition of RT. Metabolized by CytP450 (mostly 3A4). Activity limited by resistance and not used often anymore.

Class side effects: skin rashes - steven johnson syndrome; hepatitis

Question 6

NRTIs

Answer 6

nucleoside analogues or nucleoside reverse transcriptase inhibitors. Reverse tranascriptase inhibitors also work on HBV - remember you can get a flare up of HBV after d/c an NRTI.

Includes abacavir (ABC), emtricitabine (FTC), lamivudine (3TC), didanosine, stavudine, tenofovir (TDF), tenofovir alafenamide (TAF), AZT.

metabolized in the kidney except for ABC

Question 7

abacavir (ABC)

Answer 7

NRTI that causes hypersensitivity in HLA-B*5701 positive patients). Used in combination with lamivudine.

metabolized in liver not kidney

Question 8

didanosine and stavudine

Answer 8

cause pancreatitis, peripheral neuropathy; no longer used as much due to these side effects

Question 9

emtricitabine (FTC)

Answer 9

NRTI that is well tolerated (rare rash) and used in combination with tenofovir alafenamide (TAF)

Question 10

lamivudine (3TC)

Answer 10

NRTI that is well tolerated (rare rash) and used in combination with abacavir (ABC). = [3TC-ABC].

Question 11

tenofovir (TDF)

Answer 11

NRTI that can cause Fanconi syndrome and bone density loss; not used as much now due to newer version with less side effects.

Question 12

tenofovir alafenamide (TAF)

Answer 12

NRTI that can cause bone mineral density loss and nephrotoxicity but much less than Tenofovir (TDF), and causes weight gain instead. Higher intracellular levels observed than TDF - higher availability allows for lower dosing meaning less side effects.

Used in combination with emtricitabine (FTC). = [FTC-TAF]

Question 13

zidovudine (AZT)

Answer 13

NRTI that can cause bone marrow suppression (anemia) and mitochondrial toxicity

Question 14

K103N mutation

Answer 14

mutated viral reverse transcriptase which results in resistance to all NNRTIs except etravirine and rilpivirine

Question 15

M184V mutation

Answer 15

mutated viral reverse transcriptase that confers resistance against lamivudine (3TC) and emtricitabine (FTC). Also reduces fitness of the virus overall leading to 1/2 log10 reduction in HIV RNA.

Question 16

TAMs

Answer 16

mutations in RT selected by AZT and d4T but limiting to all NRTIs

Question 17

all HIV patients should be started on

Answer 17

the combination of an INSTI plus 1-2 NRTIs (ex: Dolutegravir with 3TC-ABC combo pill)