HIV Flashcards
HIV process
free virus binds to CD4 molecule and one of two coreceptors (CCR5 or CXCR4) on cell surface, virus fuses with cell –> contents empty into cell –> RT converts RNA to DNA –> Integrate incorporates viral DNA into cell DNA –> Transcription –> assembly of proteins –> budding –> breaks free of infected cell –> Maturation: protease cuts HIV protein into functional proteins
NRTIS
Zidovudine
Tenofovir & emtricitabine
Lamivudine
Abacovir
NNRTI’s
Rilpivirine
Efavirenz
PI
Ritonavir (booster) Darunivir Atezanivir Saquinivir Lopinavir/Ritonivir Indinavir Tipranovir
Fusion inhibitors
enfuvirtide
maraviroc
Integrage inhibitor
Dulutegravir
Only parenteral (SC) HIV drug
Enfuvirtide (Fuzeon)
Zidovudine MOA
thymidine analog - NRTIs
Tenovovir/emtricitabine MOA
T: adenosine
E: Cytosine
Abacavir MOA
guanisine analog
Non-peptide PI
Tipranovir
How do NNRTI’s work
bind directly to RT and inhibit - phosphorylation not needed
Phosphorylation of NRTI’s
done by the host - resistance is not due to enzyme mutation for phosphorylation
DOC for HIV dimentia
Zidovudine
DOC for HIV - 1st line
Tenofovir/Emtricitabine (don’t give with Lamivudine, same MOA)
DOC of NNRTIs
Efavirenz
Contra of efavirenz
pregnancy!!!! - teratogenic
When is rilpivirine used
substitutde for efavirenz in pregnant women
Abacavir contraindication
HLA-B-5701 (SCREEN!)
Sulfa HIV drugs
Darunivir, Tipranivir (Don’t Take)
first choice HIV therapy
Emtircitabine and tenofovir
Alternative HIV therapy
lamivudine
Abacavir
CNS penetration
Zidovudine
Toxicity of Zidovudine
CNS: H/A, Nausea, vomiting, insomnia, myalgia
Lactic acidosis and hepatotoxicity
Myelosuppression (treat w/ epogen, neupogen)
Caution of zidovudine use
other myelosuppressives: ganciclovir, ribavirin
Side effects of tenofovir/emtricitabine
Flatulence
Lamivudine use
good for HIV/HBV coinfected individuals
Monotherapy in HBV
Toxicity of Lamivudine
well tolerates: H/A, fatique, insomnia, GI; safe in pregnancy
Abacavir use
(+) lamivudine or zidovidine
Toxicity of abacavir
HYPERSENSITIVITY: test for HLA-B-5701 prior to tx.
Nausea, vomiting, diarrhea
Hypersensitivity reaction
fever, malaise, skin rash, chills, sore throat, dysnpea
Side effects of all NRTI’s
lactic acidosis & hepatotoxicity;
more likely if pt. is obese, previous liver disease or takes drugs for long time
DOC for NNRTI’s
Efavirenz
Toxicity of Efavrienz
induces CYP3A4: decrease effectiveness of BC or methadone
Teratogenic- DON”T USE IN PREGNANCY (substitute w/ rilpivirine)
Potent CYP3A4
Rifampin- inducer
Ketoconazole - p450 inhibitor
Efavirenz- CYP3A4 inducer
Rilpivirine use
replaces efavirenz in pregnant patients for NNRTIs
Side effects of rilpivirin
depression, increased cholesterol, H/A
Not recommended to use rilpivirin
hepatitis co-infection (may increase liver enzymes)
PI’s
Ritonavir (boost) Darunavir Atazanavir Saquinavir Lopinavir/ritonavir Indinavir Tipranavir
-avir
Protease inhibitor (exceptions: abacavir (NRTI) and dulutegravir (integrase inhibitor))
Common kinetics of PI
oral
combine with NRTI’s
metabolized by CYP3A4 -often given w/ ritonivir to inhibit CYP3A4 and increase PI levels
Drug interactions of PI
Drugs which induce CYP3A$ will decrease PI levels (rifampin, rifabutin, phenytoin, carbamazepine, phenobarbitol)
St. John’s Work: increases metabolism of PIs
Common toxicities of PI
altered body fat (buffalo hump and truncal obesity, facial and peripheral atroph)
Insulin resistance and hyperglycemia
Increase serum cholesterol: don’t combine with statins
Spontaneous bleeding in hemophilia A/B patient’s
Ritonavir use
booster: inhibits CYP3A4 - allows less frequent dosing and greater antiviral activity
Side effects of Ritonavir
GI
Burning, tingling and elevated liver enzymes, nausea
Contains ethanol: don’t combine with metronidazole or cephalosporins
Don’t use ritonavir with
Saquinavir (QT)
DOC for PI’s
Darunavir
Side effects of darunavir
Rash, nausea, diarrhea, H/A, bad dreams
Contra for darunavir
Sulfa allergy (use Atazenavir instead)
2nd DOC for PI
atazenavir
Dosing for Atazenavir
once/day
Side effects of Atazenavir
less effect on body fat distribution
May increase bilirubin (inhibits UGT)
Diarrhea, rash and nausea is common (maybe hyperglycemia)
Saquinavir use
alternate PI
Side effects of saquinavir
QT (don’t use with ritonavir)
GI
Saquinavir kinetics
low bioavailability- take with high-fat food or grapefruit juice to increase (inhibit P450)
Lopinavir/ritonavir side effect
diarrhea with nausea; liver enzymes may be elevated if there is pre-existing hepatic disease
Indinavir kinetics
cross-resistance with ritonavir
Side effects of indinavir
nephrolithiasis and hyperbilirubinemia (HYDRATE!!!)
Tipranavir use
tx-experienced resistant patients
Side effects of tipranavir
Intracranial hemorrhage when used with ritonavir in head injury
Sulfa
GI
Liver toxicity - more common in HBV/HCV coinfected
Fusion inhibitors
Enfuviritide
Maraviroc
MOA of enfuviritide
binds gp41 on viral envelope and prevents conformational change required for fusion
Use of enfuviritide
tx-experienced resistant patients
Enfuviritide kinetics
SUBCUTANEOUS INJECTION
no cross-resistance w/ other antiretroviral agents
well tolerated
Increases likelihood of bacterial pneumonia
Increased liklihood of bacterial pneumoniae
Enfuviritide
Flatulence
Tenofovir/emtricatabine
Depression
Rilpivirin
Hypersensitivity
abacavir
QT
saquinavir (+ ritonavir)
Myelosuppression
Zidovudine
Nephrolithiasis
Indinavir
Maraviroc MOA
binds CCR5 receptor of the CD4 T-cell and inhibits fusion
Side effect of maraviroc
rash
Don’t use maraviron
CXCR4 or mixed tropism
Integrase inhibitor
Dolutegravir
Dolutegravir use
tx-experience resistance
Side effects of dolutegravir
H/A and insomnia
Used during tx-experience resistant individuals
Tipranovir (PI)
Enfuviritide (FI)
Maraviroc (FI)
Dolutegravir (II)
