Antiretroviral therapy for HIV Flashcards
MOA of NRTI
competitive inhibition of reverse transcriptase to prevent formation of viral DNA from viral RNA
*DNA chain termination
ADRs of NRTIs
potential for lactic acidosis, hepatic steatosis, lipodystrophy
*No significant drug interactions
zidovudine (AZT)
nucleoside RTI
ADR: marrow suppression
didanosine (ddI)
nucleoside RTI
ADR: pancreatitis, neuropathy
stavudine (D4T)
nucleoside RTI
ADR: all shared ADRs of NRTIs increased; neuropathy
lamivudine (3TC)
nucleoside RTI
ADR: headache
emtricitabine (FTC)
nucleoside RTI
ADR: headache, diarrhea
abacavir (ABC)
nucleoside RTI
ADR: hypersensitivity reaction
tenofovir (TDF)
*nucleotide RTI
ADR: diarrhea, n/v, Fanconi syndrome (dz of prox renal tubules -> glucose, amino acids, uric acid, phosphate, bicarb passed into urine, instead of reabsorbed)
MOA of NNRTI
direct, non-nucleoside inhibitors of RT; doesn’t require metabolic conversion, not incorporated into viral DNA, additive effect to NRTI
ADR of NNRTI
rash, may -> Stevens-Johnson syndrome
significant drug interactions
nevirapine
NNRTI
ADR: rash, SJS, hepatotoxicity (esp CD4 > 250), modest CYP 3A4 inducer, may precipitate withdrawal in methadone maintenance patients
delaviridine
NNRTI
ADR: rash, SJS, HA, strong CYP 3A inhibitor
*rarely used d/t low potency
efavirenz
NNRTI
ADR: rash, SJS, neuropsych reaction, mod CYP 3A4 inducer, teratogenic
etravirine
NNRTI
ADR: rash, SJS, hyperlipidemia, modest CYP 3A4 inducer; CYP 2C9 and 2C19 inhibitor
rilpivirine
NNRTI
ADR: rash, HA, prolonged QT interval
MOA protease inhibitors
prevents viral protease from forming functional viral proteins necessary to mature viral particle and viral replication
ADR of protease inhibitors
GI distress, hyperglycemia, insulin resistance, hyperlipidemia, CAD, fat accumulation, hepatotoxicity
Metabolism by and inhibits CYP 3A4 (ritonavir most)
Metabolism induced by rifampin and phenytoin
Absorption reduced with rising gastric pH d/t H2-blockers and PPIs
saquinavir
PI
ADR: n/v/d
darunavir
PI
ADR: n/v, rash
indinavir
PI
ADR: n/v, nephrolithiasis
nelfinavir
PI
ADR: nausea, diarrhea
fosamprenavir
PI
ADR: nausea, rash
atazanavir
PI
ADR: increased bilirubin
Kaletra
AKA lopinavir + ritonavir
PI used to boost levels of other PIs
ADR: GI distress, hyperlipidemia
enfuviratide
fusion inhibitor; binds TM GP to prevent fusion of viral particle with CD4 cell membrane
ADR: injection site rxn and HS rxns
maraviroc
entry inhibitor; antagonist of CCR5-R on CD4 necessary for HIV entry; active if resistance to other drug classes
ADR: cough, rash, infections, substrate of CYP 3A4 (intx w PIs)
MOA integrase inhibitors
blocks integrase enzyme necessary for integration of viral DNA into cellular DNA
INSTI = integrase strand transfer inhibitor
ADR integrase inhibitors
diarrhea, nausea, HA, myositis (monitor CPK)
Truvada
2NRTIs
emtricitabine + tenofovir
Combivir
2 NRTIs
AZT + lamivudine
Epizicom
2 NRTIs
ABC + lamivudine
Trizivir
3NRTIs (not recommended)
AZT + lamivudine + ABC
Atripla
NNRTI + 2NRTI
efavirenz + emtracitibine + tenofovir
Complera
NNRTI + 2NRTI
rilpivirine + emtracitibine + tenofovir
Who to test for HIV drug resistance and what to test for?
All HIV-infected people when they enter care
Genotype testing for ARV-naive patients
Look for mutations in RT and protease genes and INSTI resistance
Regimen for pregnant women
lopinavir/ritonavir (Kaletra) + AZT/lam (Combivir)
*PI may increase hyperglycemia risk
When is transmission of HIV from pregnant woman to infant most likely?
During labor/delivery
Regimen for infant of HIV+ mother
AZT for first 6 weeks of life
Teratogenic ARV drug
efavirenz
Pre-exposure prophylaxis for high-risk adults
Truvada
Post-exposure prophylaxis for occupational exposure
3 or more drugs
for all exposures
Post-exposure prophylaxis for non-occupational exposure (sex, drugs)
3 or more active drugs if source patient known to be HIV+ or exposure event high risk for transmission
When to start post-exposure prophylaxis
Within 72 hours of exposure and continue for 4 weeks
with follow-up HIV-Ab testing for 4-6 months post-exposure