HIV Therapy Flashcards
Who gets antiretroviral therapy?
Everyone!
When should you consider deferral of ART?
Significant barriers to adherence
Comodbidities complicate or prohibit ART
“Elite controllers” and long-term non-progressors (very few)
What are classes of antiretroviral agents?
- Coreceptor binding inhibitors
- Fusion inhibitors
- Reverse transcription inhibitors (nucloside/nuclotide and non-nuclotide)
- Integrase inhibitors
- Protease inhibitors
What agent(s) are in class of Co-receptor Binding inhibitors?
Maraviroc
What is the mechanism of action of Maraviroc?
Binds CCR5 coreceptor, blocking HIV binding to host cell for entry
Is Maraviroc effective against all HIV-1?
Only works against CCR5, inactive against X4 or dual tropic virus
What should be done before giving Miraviroc?
“Trofile” to determine if virus is CCR5, CXCR4, or D/M
What agent(s) are in class of Fusion inhibitors?
Enfuvirtide
What is the mechanism of action of Enfuvirtide?
Prevents conformational change in gp41 that allows fusion of viral and host membranes
What is a major deterrent to use of Enfuvirtide?
Subcutaneous injection twice daily
What are side effects of Enfuviritide?
Subcutaneous seromas, discomfort at injection site
What agent(s) are in class of Nucleoside/nucleotide RT inhibitors (NRTIs)?
Zidovudine (AZT) DDI/D4T (didanosine, stavudine) 3TC/FTC (lamivudine, emtricitabine) Abacavir (ABC) Tenofovir (TDF)
What is method of action of NRTIs?
Analogs of nucleotide residues A, T, G, C competitively bind to active site of RT and cause chain-termination
What is a side effect of all NRTIs (but especially D4T/DDI)?
Mitochondrial toxicity
What is the clinical presentation of mitochondrial toxicity?
Neuropathy Myopathy Lactic acidosis Pancreatitis Lipodystrophy/Lipoatrophy (Buffalo hump, facial wasting, no subcutaneous fat, visceral fat deposition)
What are side effects of AZT?
Anemia, leukopenia
Anorexia, nausea, diarrhea
Headache, fatige
Myositis, weakness
What population still receives AZT?
Pregnant women
What are side effects of DDI/D4T?
Mitochondrial toxicity
Pancreatitis
Peripheral neuropathy
Hepatitis
What are side effects of 3TC/FTC?
Not sure, always given with other drugs
What are most common NRTIs prescribed today?
Abacavir
Tenofovir
What are side effects of Abacavir?
Hypersensitivity reaction - appears flu-like
Should you rechallenge someone that had hypersensitivity reaction with Abacavir?
NO - can die
What should you test for before you give Abacavir?
HLA B*5701 (if positive, predisposed to hypersensitivity reaction)
What are side effects of Tenofovir?
Asthenia (general weakness)
Flatulence, abdominal pain
Impaired renal function (different dosing requirements or don’t give to someone with impaired renal function)
What agent(s) are in class of Non-nucleoside RT inhibitors (NNRTIs)?
Nevirapine
Efavirenz
Etravirine
Rilpivirine
What is the mechanism of action of NNRTIs?
Binds at site near but distinct from catalytic site of RT enzyme and inhibits functionality
What are side effects of Nevirapine?
Rash, can progress to Stevens-Johnson
Severe hepatotoxicity
Potent induced of CyP450
Who should not receive Nevirapine?
Women with CD4 >250, Men with CD4 >400
Greater risk of hepatotoxicity
What are side effects of Efavirenz?
CNS: Insomnia, vivid dreams, difficulty concentrating, hallucinations/psychosis Rash, hepatotoxicity False-positive cannabinoid test Teratogenic CyP450 interactions
What are side effects of Etravirine?
Rash
Nausea
CyP450 interactions
What are side effects of Rilpivirine?
Insomnia (less than Efavirenz)
Rash
What should be taken into account when stopping NNRTI therapy?
Have long half life, leading to effective monotherapy when NNRTI-based triple drug regimen is stopped
Increases likelihood of resistance to NNRTIs!
What agent(s) are in class of Integrase inhibitors?
Raltegravir
Elvitegravir
Dolutegravir
What is the mechanism of action of Integrase inhibitors?
Inhibits catalytic activity of HIV-1 integrase, preventing integration of HIV DNA into host DNA
What are side effects of Elvitegravir?
Decreases CrCl
Co-formulated with TDF (another nephrotoxic drug) so do NOT give to someone with impaired renal function
What agent(s) are in class of Protease inhibitors?
Ritonavir Indinavir Nelfinavir Lopinavir/ritonavir Atazanavir Tipranavir Darunavir
What is mechanism of action of Protease inhibitors?
Prevent maturation of virions after they come out of host cells
What is unique about Ritonavir?
Rarely used along as PI
Acts to “boost” levels of other PIs by inhibiting CyP450 3A4
What are the side effects of Ritonavir?
GI: nausea, diarrhea, taste disturbance
Hyperglycemia
Hyperlipidemia
Fat maldistribution (lipoatrophy)
What are the side effects of Indinavir?
Nephrolithiasis (kidney stones)
What is unique about Nelfinavir?
Doesn’t require boost by Ritonavir
What is unique about Lopinavir?
Coformulated with Ritonavir, cannot achieve effective levels on its own
What are side effects of Atazanavir?
Lipid-sparing Asymptomatic hyperbilirubinemia (jaundice without other symptoms)
What are side effects of Tipranavir?
Rash
Hepatotoxicity
Rare intracranial hemorrhage
What are side effects of Darunavir?
Skin rash, Stevens-Johnson
Hepatotoxicity
What are side effects of Nelfinavir?
Really bad diarrhea
What is the preferred drug regimen for most patients?
2 NRTIs + 1 NNRTI, PI, or II
What is the preferred dual-NRTI pairs?
TDF/FTC (tenofovir/emtricitabine)
What are alternative dual-NRTI pairs?
ABC/3TC (abacavir/lamivudine) - risk of hypersensitivity rxn, possible risk of cardiovascular events
ZDV/3TC (AZT/lamivudine) - only really used for pregnant women
What are the NNRTI based triple drug regimens?
EFV (efavirenz) + TDF/FTC
What are the PI based triple drug regimens?
ATV/r (Atazanavir boosted with ritonavir) + TDF/FTC
DRV/r (Darunavir boosted with ritonavir) +TDF/FTC
What are the Integrase inhibitor triple drug regimens?
DTG (dolutegravir) +ABC/3TC
DTG (dolutegravir) + TDF/FTC
EVG (elvitegravir)/COBI/TDF/FTC = all coformulated together as Stribild
RAL (raltegravir) + TDF/FTC
What is an indication of therapy success?
Rapid viral load reduction (>1 log 10 decrease in 1-4 months)
What do you do when you have treatment failure and patient is adherent?
Test for resistance while on failing regimen
Genotypic and phenotypic testing
