All lectures: other HIV agents

su, shah, and horace

what is the anti-HIV fusion inhibitor

enfuvirtide

enfuvirtide is a _____ drug

polypeptide

Enfuvirtide binds to ____ to prevent the creation of an entry pore for the capsid of the virus, keeping it out of the cell.

gp41

Enfuvirtide binds to gp41 to….

prevent the creation of an entry pore for the capsid of the virus, keeping it out of the cell.

what drug is this?

enfuvirtide

what are the key proteins involved in the HIV entry process

CD4

gp120

CCR5

CXCR4

gp41

what is CD4

a protein receptor found on the surface of helper T cells in the human immune system

what is gp120

a protein on HIV surface that binds to the CD4 receptor

what is CCR5

a second receptor found on the surface of CD4+ cells

what is CXCR4

chemokine co-receptor found on CD4+ cells

what is gp41

a HIV protein, closely associated with gp120, that penetrates the cell membrane

what is the CCR5 antagonist

maraviroc

CCR5 is a member of the ____ family

beta-chemokine receptor

maraviroc is an ____ inhibitor

entry

maraviroc is a _____ of the CCR5

negative allosteric modulator

maraviroc does not compete with CCR5 (directly or indirectly)

directly

MOA of maraviroc

alters the structure of CCR5 receptor, makes it less likely to bind to the HIV virus (which inhibits it from entering the cell)

what drug is this?

maraviroc

T/F: everyone has the same kinds and amounts of receptors on their T cells

false

maraviroc ADE

upper resp infections

orthostatic HTN

hepatotoxicity

maraviroc dosing options

150 mg BID

300 mg BID

600 mg BID

maraviroc should be dosed at 150 mg BID when given with which drugs

CYP3A4 inhibitors:

• protease inhibitors (not including tipranavir + ritonavir)

• ketoconazole

• itraconzaole

• clarithromycin

• nefazodone

• telithromycin

what dose of maraviroc should be used when it is co-administered with CYP3A4 inhibitors?

150 mg BID

maraviroc should be dosed at 300 mg BID when given with which drugs

tipranavir + ritonavir

nevirapine

all NRTIs

enfuvirtide

what dose of maraviroc should be used when it is co-administered with tipranavir + ritonavir, nevirapine, all NRTIs, and enfuvirtide?

300 mg BID

maraviroc should be dosed at 600 mg BID when given with which drugs

CYP3A4 inducers:

• efavirenz

• rifampin

• carbamazepine

• phenobarbital

• phenytoin

what dose of maraviroc should be used when it is co-administered with CYP3A4 inducers?

600 mg BID

what test must be done before a pt can start maraviroc therapy and what does it do?

Trofile test

tells which types of receptors the person has because you can only take it if the pt has CCR5 receptors

what drug is this

cobicistat

cobicistat is an analog of which HIV protease inhibitor?

ritonavir

what changes to ritonavir lead to the formation of cobicistat?

Valine moiety is exchanged for a 2-morpholinoethyl group, and the backbone hydroxyl group is removed

cobicistat does not have any activity against ___

HIV

cobicistat can inhibit which CYP

CYP3A4

cobicistat is able to ____ the plasma conc of other co-admin anti-HIV drugs WITHOUT causing cobicistat resistant mutations in the HIV virus

increase

cobicistat is able to increase the plasma conc of other co-admin anti-HIV drugs WITHOUT causing ______ in the HIV virus

cobicistat resistant mutations

can you use cobicistat alone to treat HIV

hell no that shit dont have any anti-HIV properties by itself #lameasf

cobicistat inhibits intestinal transport proteins which leads to…

increased overall absorption of several anti-HIV medications

cobicistat inhibits liver enzymes that are responsible for inhibiting which HIV integrase inhibitor?

Elvitegravir (EVG)

cobicistat + elvitegravir leads to…

higher concentrations of Elvitgravir are achieved in the body with lower dosing, and enhance Elvitgravir's viral suppression while diminishing its adverse side effects

what is the four drug, fixed dose combo HIV treatment

Elvitegravir/ Cobicistat/ Emtricitabine/ Tenofovir

the quad pill is also known as

stribild

what are the medications that are in the quad pill/ stribild

Elvitegravir/ Cobicistat/ Emtricitabine/ Tenofovir

co-administration of cobicistat + TDF is not recommended for which pts

CrCl < 70

ADE of cobicistat

increases in SCr (reversible when medication is stopped)

co-admin of cobicistat + ATV can only be taken if the pt…

weighs more than 77 lbs

co-admin of cobicistat + darunavir can only be taken if the pt…

weighs 88 lbs or more and is older than 3 years old

which drug is the cytochrome inhibitor

cobicistat

MOA of fostemsavir

it attaches to the gp120 protein on the outer surface of HIV to block HIV from entering the immune cells

fostemsavir is a prodrug of…

temsavir

what is the advantage of using fostemsavir

the unique MOA should confer activity against all strands of HIV that are resistant to other anti-retrovirals

MOA of ibalizumab

monoclonal antibody post attachment inhibitor

ibalizumab dosing

IV infusion of 15-30 mins every 2 weeks

ibalizumab is only for which pts

experienced and last ditch effort