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Infectous Disease > Intro Antiretrovirals Dr. Cluck EXAM 4 > Flashcards

Intro Antiretrovirals Dr. Cluck EXAM 4 Flashcards

1
Q

OBJECTIVES

A

-Classify antiviral agents
-Regimen for PrEP (Pre-exposure prophylaxis) and PEP (post-exposure prophylaxis

-Adverse effects

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2
Q

HIV
probably not on the EXAM

A

-Retrovirus -> classified as Lentivirus
-HIV-1 is the majority in the world
-HIV-2 mostly in West Africa

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3
Q

Epidemiology of HIV

A

-35-37 million globally
-8 million did not know they have HIV
-24.5 million receiving treatment

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4
Q

How is HIV transmitted?

A

-Sexual contact (>80%); MSM (70%)
-Injection Drug Use
-Transfusion of contaminated blood or blood products
-Perinatal transmission (also known as vertical transmission or MTCT) - 40% transmission if the mother is not on antivirals, with meds it is less than 1%

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5
Q

Transmission rates for HPV, HCV, and HIV?

A

Rule of 3 !!!
HBV - Hep B: 30%
HCV - Hep C: 3%
HIV: 0.3%

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6
Q

What are the guideline recommendations for treatment after occupational HIV exposure - PEP?

A

PEP
28 days of
tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) + raltegravir BID
OR dolutegravir QD

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7
Q

Why might Ralegravir in the PEP therapy be a problem for patients?

A

-Patients tend to forget the second dose of the day, which affects the efficacy of the drug

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8
Q

What is the recommended prophylactic treatment prior to HIV exposure?

A

PrEP
-tenofovir disoproxil fumarate/emtricitebine
-tenofovir alafenamide/entricitrabine
-cabotegravir (Cabenuva)

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9
Q

What are the symptoms of an acute HIV infection?

A

-developed in 2/3 of infected patients
-“mononucleosis-like” (mono: EBV disease)
-flu-like symptoms

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10
Q

What are the symptoms of Acute Retroviral Syndrome?

A

2-4 weeks after HIV exposure
-Fever (present in 80-90%)
-Rash, often erythematous and maculopapular
-Fatigue
-Pharyngitis (with or without exudate)
-Generalized lymphadenopathy (swollen lymph nodes)
-Myalgia/arthralgia (muscle/joint pain)
-Mucocutaneous ulceration (cancer sores, lesions)

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11
Q

What is the timeline of the HIV infection?

A
  1. Initial peak - wide dissemination of the Virus -> acute HIV syndrome symptoms + seeding of lymphoid organs
  2. Clinical Latency
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12
Q

How should every HIV patient be examined?
NOT ON EXAM

A
  • a complete medical history
  • physical examination
  • laboratory evaluation
  • counseling regarding the implications of HIV infection
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13
Q

What are the labs to evaluate in an HIV patient?
NOT ON EXAM

A

-HIV antibody testing
-CD4 T-cell count (or CD4 %)
-Plasma HIV RNA (viral load)
-CBC, chemistry profile, transaminase levels, BUN (blood urea nitrogen)
and creatinine, urinalysis, and serologies for
hepatitis A, B, and C viruses
-Fasting blood glucose and serum lipids

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14
Q

What is the HLA-B*5701 test?

A

-the test tells if a patient is likely to have an allergic reaction to abacavir

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15
Q

What could be the outcome when treating a HLA-B*5701 allele-positive patient with abacavir?

A

GI manifestation (symptoms)
respiratory manifestation
overlapping manifestation
-> could be fatal!

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16
Q

What is the Trofile assay?

A

-HIV-1 phenotyping test to determine the tropism (ie, CCR5 or CXCR4) of the virus in patients being considered for CCR5 antagonist therapy (Maraviroc)

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17
Q

What is the maximum time window after exposure a patient should start PEP therapy?

A

Maximum of 72h (supported by weak data) -> as soon as possible

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18
Q

Why is it important to identify and treat HIV patients?

A

Because if the virus is controlled, the patient can not transmit the virus

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19
Q

What are the 2 oral drugs approved for PrEP?

A

-tenofovir alafenamide/entricitrabine
-cabotegravir

-not for women acquiring HIV through the vagina treated for !PrEP! due to drug concentration in the vagina (PEP works, normal treatment works)

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20
Q

Which patient population should not be treated with oral PrEP drug TAF/emtricitabine or cabotegravir?

A

Has not yet been proven to be effective in receiving HIV through vaginal sex (has only been studied in MSM and transgender women) because of the genital drug concentration

TDC/FTC is the only FDA-approved drug for individuals acquiring HIV through the vagina

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21
Q

Which drugs are approved for all patient populations?

A

-tenofovir disoproxil fumarate/emtricitebine (TDF/FTC)
-cabotegravir??? -> does it work in cis women??

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22
Q

What is the difference in mechanism between TDF and TAF?

A

-TDF is converted to tenofovir (TFV) but stays in the plasma (more side effects, and higher dose needed)
-300 mg
-TAF mainly converts to TFV in the lymphocytes (90%) - 25 mg

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23
Q

Antiretroviral drug classes

A

-Nucleoside/tide reverse transcriptase inhibitors (NRTIs)
-Non-nucleoside reverse transcriptase inhibitors (NNRTIs
- Protease Inhibitors (PIs)
-Integrase Inhibitors (INSTIs)
-Fusion Inhibitors
-Chemokine receptor antagonists (CCR5)

24
Q

What are the most important NRTIs?

A

-Retrovir (zidovudine/AZT) - clinically relevant bc of IV and PO formulation
-Ziagen (abacavir/ABC)
-Epivir (lamivudine/3TC)
-Emtriva (emtricitabine/FTC)
+
tenofovir disoproxil (TDF) and tenofovir alafenamide (TAF)

25
Q

What is the indication of the IV drug form of Retrovir?

A

prevent mother-to-child transmission

26
Q

Which NRTIs are interchangeable?

A

Epivir (3TC) and Emtriva (FTC)

27
Q

What are the toxicities associated with NRTIs?

A

-Lactic Acidosis due to mitochondrial toxicity, elevated acetate, low pH/bicarbonate, N/V, shortness of breath, if untreated
can lead to death

-Hepatomegaly with steatosis
Enlarged liver with a build-up of triglycerides and other fats inside the liver cell

-> not common

28
Q

Toxicity of Zidovudine, Didanosine, and Stavudine

A

-Zidovudine: Anemia, neutropenia !!!, headaches, malaise (feeling weak)

-Didanosine: Non-cirrhotic portal hypertension, pancreatitis !!, CD4 toxicity with TDF (not on the exam, but on NAPLEX)

-Stavudine: Peripheral neuropathy, mitochondrial toxicity, lipoatrophy (not on the exam but on NAPLEX)

29
Q

Toxicity of Abacavir

A

Hypersensitivity (need to be tested, GI and respiratory manifestation can be fatal), increased risk of MI?
-Abacavir is less effective at high viral load

30
Q

Toxicity for Lamivudine and Emtricitabine

A

-generally well-tolerated
-N/V, diarrhea

31
Q

Toxicity of Tenofovir (TDF and TAF)

A

-for TDF: Renal dysfunction (Fanconi’s syndrome), Decreased bone mineral density

-tenofovir alafenamide (TAF) has significantly less impact on kidneys and bone (less systemic bioavailability) !!!

32
Q

What are the important NNRTIs?

A

1st GENS:
Sustiva (efavirenz)
Viramune (nevirapine/NVP)

2nd GENs:
Intelence (etravirine/ETR)
Edurant (rilpivirine/RPV)
Pifeltro (doravirine/DOR)

33
Q

Which oral drug formulation requires an acidic environment?

A

-Edurant (Rilpivirine)

-has to be taken with a meal (promotes gastric acid secretion?)
-Contraindicative with PPIs
-also not effective when the viral dose is high or the CD4 count is low

34
Q

What is the best patient population to use Rilpivirine?

A

-older patients
-HIV well is controlled
-adherent
-not PPI or antacids-dependent

35
Q

NNRTI Class Toxicities

A

-Hepatotoxicity with Nevirapine
-Rash

-CNS effects specifically with Efavirenz
typically resolves in the first month of therapy (but in reality, it takes longer - vivid dreams)
CAUTION in patients with psychiatric disease
Increased suicidality

36
Q

Which drug is most likely to cause vivid dreams?

A

Efavirenz (Sustiva) (NNRTI)

37
Q

How should Efavirenz be taken?

A

-on an empty stomach
-it increases the concentration when taken w/o food
-> higher risk

38
Q

Important Advantages of Pifeltro (doravirine/DOR) latest NNRTI

A

-not as many DDI, no food interactions
-once daily
-CNS safe

Disadvantage:
paired with the older version of tenofovir (TDF) or lamivudine (3TC)
no safety data at pregnancy
no data on patients who have been already on antivirals before (which is practice)

39
Q

Important Protease Inhibitors

A

Reyataz (atazanavir/ATV) - blocks conjugation of bilirubin -> JAUNDICE
!!!Prezista (darunavir/DRV - most often used in clinic
Viracept (nelfinavir/NFV) - causes diarrhea long-lasting
Invirase (saquinavir/SQV)
Norvir (ritonavir/RTV)

Combine with Ritonavir or Cobicistat

40
Q

PIs not often used

A

Crixivan (indinavir/IDV) - causes kidney stones (take w/ plenty of water)
Kaletra (lopinavir/LPV PLUS
ritonavir) - causes bad diarrhea
Aptivus (tipranavir/TPV) - used when patients have antiviral drug resistance
Lexiva (fosamprenavir/FPV

COMBINE with ritonavir or cobicistat

41
Q

Why should Protease inhibitors ALWAYS be used with Ritonavir?

A

-has antiviral activity but it is used as a BOOSTER (given in low doses)

-it is a CYP-inhibitor -> thereby increasing the Bioavailability of Proetease inhibitors (have poor Bioav.)

42
Q

What to look out for when patients use ritonavir?

A

DDI
f.e. anti-coagulants -> increased concentration due to Ritonavir-induced-CYP-inhibition -> BLEEDING

43
Q

Why is darunavir (DRV) used over Atazanavir (Reyataz)?

A

Because Atazanavir causes Jaundice, nephrotoxicity, and gout stones

44
Q

Which NRTI can cause nephrotoxicity?

A

Tenofovir

for dialysis patients: could use Abacavir instead -> only NRTI that is not cleared renally -> cleared by ADH

45
Q

What are the adverse effects of Protease Inhibitors?

A

Lipodystrophy (long-term) includes
-metabolic (hyperglycemia and hyperlipidemia)
-morphologic (fat atrophy and fat deposition) abnormalities
-> often caused by Ritonavir

46
Q

What does a regimen for PEP look like?

A

-mostly two NRTIs + 3rd drug - often Integrase inhibitors

47
Q

Important Integrase inhibitors

A

-Isentress/Isentress-HD (raltegravir/RAL)
-Genvoya/Stribild (elvitegravir/EVG)* used with Cobicistat- CYP3A4 inh. (ELVIS needs a friend)
-Tivicay (dolutegravir/DTG)
-Biktarvy (bictegravir/BIC)* MOST COMMONLY used
-Cabenuva (cabotegravir/CAB) !!IV injectable!!

48
Q

Why are Integrase inhibitors preferred as 3rd antiviral drug in the regimen?

A

-often single dose
-well tolerated
-very potent

49
Q

What is the most commonly used Integrase inhibitor and WHY?

A

-Biktarvy (bictegravir/BIC)
-single dose
-it has the NEW tefonovir (TAF/TDF) combi ALL-in-ONE tablet

50
Q

What is special about Cabenuva (cabotegravir/CAB)?

A

-newest Integrase inhibitor
-it is INJECTABLE
-it comes with Rilpivirine (NNRTI) so 2 injections into the muscle -> for TREATMENT
-every 8 weeks

51
Q

How is Cabenuva used for PrEP?

A

-just a single dose of Cabenuva w/o Rilpivirine
-every 8 weeks (the drug has a very long half-life)

52
Q

Which drug is considered an Entry inhibitor?

A

Selzentry (maraviroc)
-need Trofile assay to check if the pt is predominantly CCR5 (+) !!!!!

53
Q

Which drug is considered a Fusion inhibitor?

A

Fuzeon (enfuvirtide/T-20)
-sub-cutaneous, needs to be reconstituted
-no known Drug interactions

54
Q

What is special about Ritonavir and Cobicistat?

A

-They boost anti-retroviral agents via CYP3A4 inhibition

-CAUTION: any drug metabolized by CYP3A4 will have a Drug interaction !!!

55
Q

New regimen:

A

3-Drug:
Integrase Inhibitor + 2x NRTIs:
Bictegravir (BIC) includes FTC (NRTI) and TAF (new tenofovir, NRTI)

NNRTI + 2x NRTI:
Doravirine (NNRTI) w/ lamivudine (3TC, NRTI) and TDF (old tenofovir, NRTI)

Protease Inhibitor + Cobicistat (boost) + 2x NRTI:
Darunavir (PI) + COBI (boost) w/ FTC (NRTI) and TAF (new tenefovir, NRTI)

56
Q

New 2-Drug Regimen

A

2-Drugs:
Integrase Inhibitor with NNRTI
dolutagravir (Integrase Inh.) with rilpivirine (RPV, NNRTI)
-> REMEMBER rilpivirine requires an acidic environment, so don’t use it when pt is on PPI or antacids (+ not appropriate with high viral load)

Integrase Inhibitor with NRTI:
dolutagravir (Intergrase Inhibitor) + lamivudine (3TC)

Infectous Disease (29 decks)

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