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Microbiology Part 2 > Lec 35 HIV Treatment > Flashcards

Lec 35 HIV Treatment Flashcards

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1
Q

What is mech of NRTI action?

A

NRTI = nucleoside reverse transcriptase inhibitors

- compete with native nucleotides as substrates for RT

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2
Q

What are side effects common to NRTIs?

A
  • mitochondrial toxicity: muscle weakness, mental state change, pancreatitis, lactic acidosis
  • dyslipidemia
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3
Q

What is a side effect specific to AZT [zidovudine]?

A

anemia

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4
Q

What is a side effect specific to 3TC [lamivudine]?

A

minimal toxicity

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5
Q

What is a side effect specific to FTC [emtricitabine]?

A

minimal toxicity

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6
Q

Which two NRTIs are preferred in ARV-naive patients?

A
  • FTC [emtricitabine]

- TDF [tenofovir]

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7
Q

What is a side effect specific to ABC [abacavir]?

A
  • hypersensitivity reaction in HLA B-5701 [can be fatal]
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8
Q

What is a side effect specific to tenofovir [TDF]?

A
  • renal toxicity [major one]

- also osteopenia

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9
Q

What sides effects of didanosine [ddI]?

A
  • higher risk mitochondrial toxicity
  • peripheral neuropathy
  • insulin resistance
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10
Q

What side effects of stavudine [d4T]?

A
  • higher risk of mitochondrial toxicity
  • lipoatrophy
  • insulin resistance
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11
Q

What were early principles of HIV treatment?

A

first: treat early and treat hard
then: treat based on CD4/VL/symptoms

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12
Q

What are the downside of NNRTIs?

A
  • resistance develops easily

- all have interactions with CP450

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13
Q

What are side effects specific to nevirapine [NVP]?

A
  • hypersensitivity rxn [hepatitis, rash, mucoal alteration]

- rxn more common in women and pts with relatively high CD4

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14
Q

What are side effects specific to efavirenz [EFV]?

A
  • neuropsychiatric symptoms
  • potential teratogen
  • lipid elevation
  • rash
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15
Q

What are the 2 NNRTIs?

A
  • nevirapine [NVP]

- efavirenz [EFV]

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16
Q

What is mech of action of NNRTIs?

A

NNRTIs = non-nucleoside reverse transcriptase inhibitors

- act as allosteric inhibitor to bind RT

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17
Q

What is mech of action of PIs?

A

PIs - protease inhibitors

- block viral proteases involved of cleavage of viruses from non-infectious to mature infectious form

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18
Q

What are class side effects of PIs?

A
  • dyslipidemia
  • lipohypertrophy [accumulate fat around waste]
  • CP450 interactions
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19
Q

What are side effects specific to atazanavir [ATV]?

A
  • indirect hyperbilirubinemia [main effect]

- nephrolithiasis

20
Q

What are side effects specific to darunavir [DRV]?

A

rash

21
Q

What are side effects specific to fosamprenavir [FPV]?

A

rash

22
Q

What are side effects specific to lopinavir/ritonavir [LPV/r]?

A

GI intolerance

23
Q

What are side effects specific to tipranavir [TPV]?

A

hepatotoxicity

24
Q

What are side effects specific to rotonavir [RTV}?

A
  • potent CP450 inhibitor

- use only as PK booster at low dose –> no longer used for antiretroviral effect

25
Q

What are the 6 PIs?

A
  • atazanvir [ATV]
  • darunavir [DRV]
  • fosamprenavir [RPV]
  • lopinavir/ritonavir [LPV/r]
  • tipranavir [TPV]
  • ritonavir [RTV]
26
Q

What are the first line PIs for ARV-naive?

A
  • atazanvir [ATV]

- darunavir [DRV]

27
Q

What is mech of integrase inhibitors?

A
  • inhibit integration of HIV DNA with host DNA
28
Q

What are INSTIs?

A

INSTI = integrase strand transfer inhibitor

29
Q

What are the 3 INSTIs?

A
  • raltegravir [RAL]
  • elvitegravir [EVG]
  • Dolutegravir
30
Q

How is elvitagravir [EVG] administered?

A
  • only as combination pill with:
  • – NRTIs tenofovir and emtricitabine
  • – CP450 inhibitor cobicistat
31
Q

What is cobicistat?

A

A CP450 inhibitor given in combination pill with elvitegravir, tenofovir, emtricitabine

32
Q

What is the first line INSTI in ARV-naive?

A

raltegravir [RAL]

33
Q

What is mech of action maraviroc [MVC]? Who does it work for?

A

MVC = a CCR5 antagonist
only works if patient has CCR5 viral tropism –> need to do viral tropism assay
- prevents HIV from attaching to host cell by CCR5 co-receptor

34
Q

What is enfuviritide [T20]? mech? downsides?

A

enfuviritide [T20] = fusion inhibitor
- inhibits fusion of HIV with host cell membrane [so HIV can’t enter host cell]

downsides: injectable, no serious side effects but can have local inject side reaction

35
Q

What are current treatment indications for HIV?

A
  • ART recommended for all HIV infected to reduce risk of disease progression and prevent further transmission
36
Q

What are the current 4 preferred regimens for ARV naive?

A
  • tenofovir/emtricitabine, atazanavir, ritonavir
  • tenofovir/emtricitabine, darunavir, ritonavir
  • tenofovir/emtricitabine/efavirenz [single pill]
  • tenofovir/emtricitabine, raltegravir

all use tenofovir/emtricitabine as backbone [except the 3rd which has a single pill with those 2 + efavirenz]
use of ritonavir is as for PK
each is once a day

37
Q

Why do you use genotypic assay for ARV resistance early on in infection but not so much later on?

A
  • later on in infection have lots and lots of mutations that may interact with each other or cancel each other out so much harder to interpret
38
Q

What are ways you can test for resistance?

A
  • genotypic assay for ARV resistance

- phenotypic resistance testing

39
Q

What does phenotypic resistance testing do?

A
  • look at inhibition of viral replication over different drug conc, compare patient to wild type lab strain
    compare based on IC50 = conc of drug at which inhibit 50% of viral replication and decide if its resistant or not based on the difference in IC50 [the “fold change”]
40
Q

What is downside of resistance assay?

A

resistance assays cannot detect minority resistance population –> what might be a minority without treatment will become a majority with treatment when the non-resistant dies off and you are only left with the resistant

41
Q

What is primary prophylaxis?

A

give prophylactic treatment for disease pt has never had

42
Q

What is prophylactic treatment for pneumocystis jiroveci with HIV? When do you give it?

A
  • trimethoprim-sulfamethoxazole

- give at CD4 < 200

43
Q

What is prophylactic treatment for mycobacterium avium-complex with HIV? When do you give it?

A
  • azithromycin

- give at CD4 < 50

44
Q

How do you prevent with ARV

A
  • give treatment as prevention
  • post-exposure prophylaxis [PEP]
  • prevention of mother to infant transmission of HIV
  • pre exposure prophylaxis
45
Q

What drugs do you give in pre-exposure prophylaxis [PrEP]?

A

TDF [tenofovir] or TDF/FTC [tenofovir/emtricitabine]

46
Q

What are the 5 NRTIs? mnemonic? KNOW THIS!

A

ZELAT

  • zidovudine
  • emtricitabine
  • lamivudine
  • abacavir
  • tenofovir

Microbiology Part 2 (30 decks)

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