HIV

Question 1

What are the stages of HIV replication and how is this useful?

Answer 1

Stage 1+2: Binding of virus to CD4 receptors and CCR5/CXCR4 co-receptors on the surface of CD4 host cell and fusion of HIV to CD4 cell membrane. CCR5 antagonists and fusion inhibitors work here
Stage 3: HIV RNA is converted to HIV DNA by reverse transcriptase. It can then enter the CD4 cell nucleus. Reverse transcriptase inhibitors work here (NRTIs and NNRTIs)
Stage 4: integration - integrate i s release and used to insert HIV DNA into the host cell. Integrase inhibitors used here.
Stage 5: Host cell machinery is used to transcribe and translate HIV DNA into HIV RNA. No meds for this stage
Stage 6:new HIV RNA, proteins and enzymes (including protease) move to cell surface and assemble into immature HIV. No meds for this stage
Stage 7 - immature HIV pushes out of the CD4 cell and protease breaks up the long viral protein chains, creating a mature virus that can then infect other cells. Protease inhibitors used here.

Question 2

Enfuvirtide, maraviroc and vicriviroc are what type of ARTs?

Answer 2

Fusion/Penetration blockers/CCR5 antagonists.

Question 3

What are 2 NNRTIs? What stage do they work at?

Answer 3

Efavirenz, Rilpivirine
Stage 3 - reverse transcriptase inhibitors.

Question 4

What are some common NRTIs?

Answer 4

Abacavir, emtricitabine, lamivudine, TDF, TAF, zidovudine.

Question 5

What are some examples of INSTIs and where do they act?

Answer 5

Bictegravir, dolutegravir, elvitegravir and raltegravir

Stage 4 - Integrase strand transfer inhibitor

Question 6

What are some common Protease inhibitors (PIs) and where do they work?

Answer 6

Atazanavir, Darunavir, Fosamprenavir, lopinavir, tipranavir.

Stage 7 - where the protease cuts the long viral strands to create a mature virus.

Question 7

What is an ART naive regimen?

Answer 7

2NRTIs (stage 3) and 1 INSTI (stage 4)

Question 8

What is an alternative ART regimen?

Answer 8

One “base” (either PI, NNRTIS or INSTI) and 2 NRTIs.

Question 9

What is Z LATTE?

Answer 9

Acronym for the NRTIs:
Zidovudine, Lamivudine, Abacavir, TDF, TAF and Etravirine

Question 10

T/F: NRTIs have a high barrier to resistance.

Answer 10

False - low. Barrier to resistance. Resistance develops easily. That’s what ART regimens usually include 2 NRTIs AND a base (PI/INSTI or NNRTI)

Question 11

Abacavir - what is key prior to prescribing this medication?

Answer 11

“A for allergies”
Patients must be screened for the HLA-B*5701 allele due to extreme risk for hypersensitivity.

Question 12

What class of antiretrovirals ends in “-tegravir”

Answer 12

INSTIs - stage 4 Integrase inhibitors

Question 13

What are some DI examples for INSTIs? Some SEs?

Answer 13

“-tegravir”
Polyvalent cations (Mg, MVI, Iron, Ca) need to be separated by 2hrs.

depression and SI.

Question 14

which has a higher barrier for resistance, INSTIs or NRTIs?

Answer 14

INSTIs.

Question 15

What is the preferred drug for treatment of HIV during pregnancy?

Answer 15

Dolutegravir (INSTI) and darunavir. (PI)

Question 16

What are some trends of AEs in INSTIs?

Answer 16

Increased SCr through inhibition of tubular secretion
Increased r/o rhabdo
Hepatotoxic.

Question 17

What is REDEN?

Answer 17

NNRITs
Rilpivirine, Efavirenz, Doravirine, Etravirine and Nevirapine.

Question 18

What class of ARTs non- competitively inhibit the conversion of HIV RNA to HIV DNA?

Answer 18

NNRTIs.

Question 19

What are some DIs with NNRITs?

Answer 19

CYP3A4 inducers like phenytoin, rifampin, carbamazepine, oxcarbazepine, phenobarbital
Acid suppressants.

Question 20

Which NNRTI has a high fail rate and should not be used with viral load > 100,000 copies or cD4 count < 200?

Answer 20

Rilpivirine.

Question 21

What are some AEs with Efavirenz?

Answer 21

NNRTI
CNS SEs like depression, SI
Increased cholesterol and triglycerides.

Question 22

When you see PIs, think:

Answer 22

DIs! PIs = DIs!
Major CYP3A4 substrate/strong inhibitors
Warnings for: Hyperglycemia, dyslipidemia, increased r/o CVD, hepatic dysfunction.

Question 23

what class of ARTs end in “-Navir”?

Answer 23

PIs (except for Atazanair and Bevirimat

Question 24

What are Ritonavir and Cobicistat?

Answer 24

ART boosters/enhancers they have many DIs!

Question 25

If the HIV strain binds to CXCR4 or is a mixed binder, will Maraviroc be effective?

Answer 25

No. Miraviroc is a CCR5 antagonist (fusion inhibitor)

Question 26

What is Fostemsavir? When is it used?

Answer 26

Attachment inhibitor. Used in combination with other ARTs in patients who are failing current therapy.

Question 27

What is a common ART regimen for treatment-naive patients?

Answer 27

2NRTI backbone
- TDF, TAF OR Abacavir
plus
-Lamivudine or Emtricitabine
And 1 INSTI
-Dolutegravir, Elvitegravir or Raltegravir

Question 28

What is the preferred medication used in the tx regimen for PEP?
What is the timeline?

Answer 28

2 NRTIs - Truvada (TDF and emtricitabine)
1 INSTI - dolutegravir or raltegravir.

Started w/in 72hrs and continue for 28 days
Test at baseline, 4-6ths, 3 mo and 6mo post exposure.

Question 29

T/F: a ART tx regimen of 2 NRTIs and 1 NNRTI is appropriate.

Answer 29

True. As long as there is a 2 NRTI combo, the “base” can be either a PI, NNRTI, or INSTI.