HIV Therapy Flashcards by Danielle Himelfarb

Who gets antiretroviral therapy?

Everyone!

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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)

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What are classes of antiretroviral agents?

Coreceptor binding inhibitors
Fusion inhibitors
Reverse transcription inhibitors (nucloside/nuclotide and non-nuclotide)
Integrase inhibitors
Protease inhibitors

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What agent(s) are in class of Co-receptor Binding inhibitors?

Maraviroc

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What is the mechanism of action of Maraviroc?

Binds CCR5 coreceptor, blocking HIV binding to host cell for entry

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Is Maraviroc effective against all HIV-1?

Only works against CCR5, inactive against X4 or dual tropic virus

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What should be done before giving Miraviroc?

“Trofile” to determine if virus is CCR5, CXCR4, or D/M

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What agent(s) are in class of Fusion inhibitors?

Enfuvirtide

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What is the mechanism of action of Enfuvirtide?

Prevents conformational change in gp41 that allows fusion of viral and host membranes

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What is a major deterrent to use of Enfuvirtide?

Subcutaneous injection twice daily

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What are side effects of Enfuviritide?

Subcutaneous seromas, discomfort at injection site

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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)

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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

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What is a side effect of all NRTIs (but especially D4T/DDI)?

Mitochondrial toxicity

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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)

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What are side effects of AZT?

Anemia, leukopenia
Anorexia, nausea, diarrhea
Headache, fatige
Myositis, weakness

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What population still receives AZT?

Pregnant women

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What are side effects of DDI/D4T?

Mitochondrial toxicity
Pancreatitis
Peripheral neuropathy
Hepatitis

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What are side effects of 3TC/FTC?

Not sure, always given with other drugs

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What are most common NRTIs prescribed today?

Abacavir

Tenofovir

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What are side effects of Abacavir?

Hypersensitivity reaction - appears flu-like

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Should you rechallenge someone that had hypersensitivity reaction with Abacavir?

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NO - can die

What should you test for before you give Abacavir?

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HLA B*5701 (if positive, predisposed to hypersensitivity reaction)

What are side effects of Tenofovir?

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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

HIV Therapy Flashcards

(54 cards)