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HIV Flashcards

1
Q

What is ART?

A

Antiretroviral therapy

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2
Q

What is AI?

A

Disease progression

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3
Q

What conditions increase the urgency of initiation of therapy?

A 
Pregnancy
AIDS-defining conditions, including HIV-associated dementia
Acute opportunistic infectoin
Lower CD4 counts
HIV-associated nephropathy
HIV-HBV co-infection
HIV/HCV co-infection
Acute/early infection
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4
Q

What are the goals of therapy?

A

Maximal and durable suppression of VL.
Restoration or preservation of immunologic function.
Improvement of QOL.
Reduction of HIV-related morbidity and mortality; prevention of opportunistic infections.
Avoidance of ADRs.
Prevent transmission.

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5
Q

What factors should be considered before selecting a regimen?

A 
Comorbid conditions
Potential ADRs
Potential drug interactions with other medications
Pregnancy or pregnancy potential
Results of genotypic drug resistance testing
HLA-B*5701 testing if considering ABC
Convenience
Financial stability
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6
Q

What is the MOA of NRTIs

A

Require intracellular phosphorylation of the 5’-triphosphate moiety to be active.
The 5’-triphosphate competes with endogenous deoxynucleotides for reverse transcriptase enzyme and prematurely terminates DNA elongation d/t modified 3’-hydroxyl group.

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7
Q

What is the BBW for NRTIs?

A

Lactic acidosis

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8
Q

How are NRTIs eliminated?

A

Renally (no CYP450 interactions or DDIs)

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9
Q

What are some ADRs of NRTIs?

A

Pancreatitis

Lipodystrophy/lipoastrophy

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10
Q

Which NRTIs have activity against Hep B?

A

3TC/FTC

TDF/TAF

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11
Q

How often are Combivir and Trizivir taken?

A

1 tab BID

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12
Q

How often are Epzicom, Truvada, and Descovy taken?

A

1 QD

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13
Q

What are the thymidine analogue NRTIs?

A

AZT/ZDV

d4T

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14
Q

Which NRTIs can be taken in pregnancy?

A

AZT/ZDV

Lamivudine

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15
Q

What are the side effects of 3TC?

A

None

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16
Q

What are the side effects of FTC?

A

Well tolerated

Skin hyperpigmentation

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17
Q

What drug should not be combined with d4T?

A

AZT/ZDV (both thymidine analogues)

ddI (similar toxicities)

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18
Q

What are the ADRs of ABC?

A

Hypersensitivity (2-9%) - flu like symptoms - happens in the morning - worsens progressively

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19
Q

Which drug do we do an HLA B*5701 test for?

A

ABC

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20
Q

How is ABC eliminated?

A

Renally as inactive metabolits

No adjustments needed

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21
Q

What are TDFs ADRs?

A

N/V
Decreased BMD, renal dysfunction, esp when used in boosted regimens (w/RTV/COBI)
Generally well tolerated

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22
Q

What are TAFs ADRs?

A

Well tolerated

Better safety profile (renal, bone) compared to TDF

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23
Q

What are NNRTIs MOA?

A

Bind non-competitively to RT and cause a conformational change.
Do not require intracellular phosphorylation and do not complete w/endogenous deoxynucleotides

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24
Q

How are NNRTIs metabolized?

A

By CYP450

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25
What is the NNRTI half-life?
Very long
26
What is a common ADR of all NNRTIs?
Rash | LFT increases
27
What are the first generation NNRTIs?
EFV | NVP
28
What are the second generation NNRTIs
ETV | RPV
29
What are the ADRs for EFV?
``` Rash (up to 10%) CNS effects Increased LFTs Increased lipids Neural tube defects if given in first 5-6 weeks of gestation. Pregnancy category D ```
30
What are the ADRs for NVP?
Do not start in women w/ >250 CD4 or men w/ > 400 d/t hepatotoxicity
31
How is EFV metabolized?
It is a P-450 substrate and inducer
32
How is NVP metabolized?
It is a P-450 autoinducer and inducer of other drugs
33
What are the DDIs of ETV?
Multiple drug interactions
34
What enzymes are ETV a substrate for?
3A4 2C9 2C19
35
What enzymes are ETV an inducer for?
3A4
36
What enzymes are ETV an inhibitor for?
2C9 | 2C19
37
What is ETV currently approved for?
Anti-retroviral experienced patients only
38
What are the ADRs for RPV?
``` Rash Depression Insominia HA Increased QT interval ```
39
Which NNRTI must be taken with a meal?
RPV | Meal must be > 500 cal
40
Which NNRTI has acid dependent absorption?
RPV | DDI with acid-reducing agents
41
How does RPV affect CYP enzymes?
It is a substrate
42
When should RPV NOT be started?
> 100,000 HIV-1 RNA copies or < 200 CD4
43
What is RPV approved for?
Anti-retroviral naive patients only
44
How should Atripla be taken?
1 QHS
45
How should Complera and Odefsey be taken?
1 QD
46
What are the ADRs of COBI?
Acute renal failure and Fanconi syndrome (when used with tenofovir)
47
What is COBI approved for?
Only to boost atazanavir and darunavir
48
Is COBI interchangable?
Not with ritonavir for all other PIs
49
What are the PK enhancers?
COBI | Ritonavir
50
What are PIs MOAs?
Block the maturation process, thereby resulting in the production of immature, noninfectious virions
51
How are PIs metabolized?
CYP-450
52
What are the GI ADRs of PIs
``` Lipodystrophy Hyperlipidemia Hyperglycemia Pancreatitis LFT increases ```
53
Why are PKs used with PIs?
PIs are poorly absorbed
54
What are the ADRs of RTV?
GI: loose stools, maybe diarrhea 1st couple of weeks then it goes away
55
How is RTV involved with CYP enzymes?
Very potent CYP450 inhibitor
56
What are the ADRs of ATV?
GI Hyperbilirubinemia Nephrolithiasis
57
Which PIs have a sulfa moiety?
DNV FPV TPV
58
What are DNVs ADRs?
GI | rash
59
Which PIs are preferred in pregnancy?
ATV | DNV
60
How is evotaz taken?
1 QD
61
How is Prezcobix taken?
1 QD
62
What is needed in addition to Evotaz and Prezcobix?
Still need 2 other agents
63
What is the MOA of entry inhibitors?
Inhibit the various steps of HIV with CD4 cells
64
What is the fusion inhibitor?
T-20
65
What are the ADRs of T-20?
Injection site reaction
66
How is T-20 administered?
SQ BID
67
Who can receive T-20?
ART experienced patients only
68
What is the CCR5 receptor antagonist?
Maraviroc
69
What are the ADRs of Maraviroc?
Hepatotoxicity +/- systemic allergic reaction (pruritic rash, eosinophilia or elevated IgE)
70
Who is Maraviroc approved for?
Patients who have CCR5 tropic virus
71
Which CYP enzyme is Maraviroc a substrate for?
3A4
72
What does Maraviroc dosing depend on?
Co-administered agents
73
What is the MOA of integrase inhibitors?
Prevent covalent bonds from forming between integrase and host DNA -> HIV integrase unable to incorporate the viral DNA into the CD4 cell chromosome -> prevention of strand transfer and viral replication
74
What are RALs ADRS?
None in clinical trial | Post marketing reports: skin rashes and severe hypersensitivity
75
Which integrase inhibitor is preferred in pregnancy?
RAL
76
How is RAL metabolized?
No p450 metabolism | Glucuronidated by UGT 1A1
77
What is EVGs ADRs?
Diarrhea
78
How is EVG used?
In combination with ARVs (PIs) in treatment experienced patients
79
What are DTGs ADRs?
Well tolerated Insomnia H/A
80
How is DTG metabolized?
Primarily metabolized by UGT 1A1
81
What are the current guideline regimen for an ART naive patient?
``` NNRTI + 2 NRTIs OR PI (booster) + 2 NRTIs OR INSTI + 2 NRTIs ```
82
What is the preferred PI regimen for an ART naive patient?
Darunavir/ritonavir + FTC/TDF OR Darunavir/ritonavir + FTC/TAF
83
What are the preferred integrase inhibitor regimen for an ART naive patient?
``` Raltegravir + FTC/TDF or FTC/TAF OR Elvitegravir/cobi/FTC/TDF OR Elvitegravir/cobi/FTC/TDF OR Dolutegravir + FTC/TDF OR Dolutegravir/abacavir/lamivudine ```
84
Which integrase inhibitor regimens can you not use if CrCl < 70?
Stribild and Genvoya
85
What labs do you get at baseline?
``` Plasma HIV RNA (viral load), CD4 count Chem-7, LFTs, CBC/diff Fasting lipids Other serologies (CMV, Toxo, Crypto, RPR, Hep A/B/C HLA B*5701 genetic screening ```
86
What do we monitor for at 2 weeks after treatment initiation?
Side effects Adherence Can obtain VL and CD4 count
87
What do we monitor at 4-6 weeks?
Side effects Adherence VL (should decrease by at least 1 log) CD4 count
88
How often should the patient be checked once stable and what is monitored?
``` Every 3-6 months VL CD4 Chem-7 CBC U/A (if on tenofovir) ```
89
What is virologic suppression?
A confirmed HIV RNA level below the limit of assay detection
90
What is virologic failure?
The inability to achieve or maintain suppression of viral replication (< 200 HIV RNA level)
91
What is incomplete virologic response?
Two consecutive plasma HIV RNA levels > 200 after 24 weeks on an ARV regimen. Baseline HIV RNA may affect the time course of response, and some regimens willl take longer than others to suppress HIV RNA levels.
92
What is virologic rebound?
Confirmed detectable HIV RNA (to > 200) after virologic suppression
93
What is persistent low-level viremia?
Confirmed detectable HIV RNA levels that are < 1000
94
What is virologic blip?
After virologic suppression, an isolated detectable HIV RNA level that is followed by a return to virologic suppression.
95
When do you consider switching the drug regimen of a patient?
When adherence, tolerability, and PK causes of treatment failure have been ruled out consider the following: - Virologic failure - Immunologic Failure - Clinical Failure - Intolerable toxicity
96
What is immunologic failure?
The failure to achieve and maintain an adequate CD4 response despite virologic suppression. Increases in CD4 counts in ARV-naive patients with intial ARV regimens are approximately 150 over the first year
97
What is clinical failure?
Occurence or recurrence of HIV-related events (after at least 3 months on HAART)

Infectious Disease (19 decks)

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