HIV treatments

Question 1

NRTI

Answer 1

HIV tx
Nucleoside or nucleotide analogs 
lack 3/hydroxyl group
need to be PHOSPHOrylated
form synthetic substrate for viral RT
Terminate DNA elongation

AE - mitochondrial toxicity

AE: lactic acidosis-hepatic steatosis syndrome (D>S>Z)
inhibits DNA polymerase gamma -> block production of mtDNA and inhibit oxidative phosphorylation complexes –> INC cytosolic lactate production

Abacavir
Didanosine
Emtracitabine - yes 
Lamivudine
Stavudine
Tenofovir - Yes
Zidovudine

Question 2

Abacavir

Answer 2

NRTI

CI: HLA-B 5701+
hypersensitivity

Question 3

Didanosine

Answer 3

NRTI
lactic acidosis
pancreatitis
neuropathy

Question 4

Emtracitabine

Answer 4

NRTI

hyper pigmentation palms and soles

Question 5

LamivuDINE

Answer 5

NRTI

tx - Hep B –> AE: HBV flare if removed abruptly

peripheral neuropathy

Question 6

StavuDINE

Answer 6

NRTI

peripheral neuropathy
lipodystrophy

Question 7

Tenofovir

Answer 7

NUCLEOTIDE RTI

tx - Hep B –> AE: HBV flare if removed abruptly

Question 8

ZidovuDINE

Answer 8

NRTI
YES - pregnancy and breastfeeding (Dec vertical transmission)

anemia
myelosuppression
granulocytothemia
lipodystrophy

Question 9

NNRTI

Answer 9

HIV tx
noncompetitive inhibitors of viral reverse transcriptase to induce conformation change –> dec activity of RT

:) reduce early use of protease inhibitors
:( prevalence of NNRTI-resistant virus
:( low genetic barrier to NNRTI to resistance

CYPs interaction

AE: JAUNDICE (liver failure within 6 wks)
stevens johnson’s syndrome

Delaviridine
Efavirenz
Etravirine
Nevirapione
RILPIVIRINE

Question 10

Efavirenz

Answer 10

NNRTI

x TB pts

AE: birth defects
CI: 1st trimester pregnancy or in women planning to conceive

CNS AE: nightmares, dizzy, psychosis

Question 11

Nevirapine

Answer 11

NNRTI

naive women with pre-tx CD4 >250
men CD>400

CI in high pre-tx CD4 counts bc INC hepatotoxity

Question 12

Delaviridine

Answer 12

NNRTI

teratogenic

Question 13

Protease Inhibitors

Answer 13

HIV tx
inhibit HIV aspartyl protease (block post-translational process/production of mature particle)

poor oral bioavailability
enhanced by high FAT meals

DDI: Rifampin
do not use CYP34A statin
like love, amor, simva (use prava, fluva)

AE: metabolic syndrome, lipodystrophy

resistance with POL gene mutations

“NAVIRs”

Question 14

RitoNAVIR

Answer 14

protease inhibitor

paresthesias

CYP450 inhibitor–> BOOST other protease inhibitors
(allows for dec dose and frequency)

Question 15

IndiNAVIR

Answer 15

protease inhibitor

nephrolithiasis
need adequate fluid intake

Question 16

Viral InteGRAse Inhibitors

Answer 16

binds Mg cofactors required for strand transfer –> blocks insertion of reverse-transcribed viral DNA into the host DNA
(prevent transcription of HIV mRNA)

mutations that alter orientation Mg ions = resistance

AE: Rhabdomyolysis

“GRAVIRs”

Question 17

RalteGRAVIR

Answer 17

Viral InteGRAse Inhibitors

yes - naive

Question 18

ElviteGRAVIR

Answer 18

Viral InteGRAse Inhibitors

only approved INTI that is CYP substrate
shortest t1/2

Question 19

DoluteGRAVIR

Answer 19

Viral InteGRAse Inhibitors

longest t1/2

Question 20

EnFUrvitide

Answer 20

Fusion Inhibitors

peptide inhibitor binds HIV surface glycoprotein g41 –> block conformation required for membrane fusion with host cell

injected twice daily

relative effectiveness at reducing viral load
resistance if mutation at HR1 region of gp41

Question 21

Mariviroc

Answer 21

CCR5 antagonist

Inhibit viral entry:
small molecule slowly-reversible antagonist of CCR5 interaction with Gp120
blocks CCR5-tropic HIV-1 entry

hepatotoxicity
CYPs

trofile assay - check CCR5 tropism before starting drung

Question 22

TX for Naive pts

Answer 22

1 NNRTI + 2 NRTI

1 PI (boosted w/ RTV) + 2 NRTI

Question 23

HIV-2 tx

Answer 23

Zidovudine

RTV boosted PIs