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PR3151 (cleefy) > IC18a PR3151 HIVAIDS > Flashcards

IC18a PR3151 HIVAIDS Flashcards

1
Q

describe HIV and what it does to the body (general)

A

lentivirus group of the retrovirus family
attacks the CD4 t cells
causes AIDS in the long term

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2
Q

Describe the mode of transmission of HIV

A

through specific fluids: genital fluids, blood, breast milk:
- sexual intercourse
- sharing of infected syringes and needles
- Mother-to-child transmission
- transfusion w/ contaminated blood

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3
Q

What patient populations/types should be tested for HIV?

A

1) individuals with unprotected sex with multiple sex partners
2) male-male sexual intercourse
3) intravenous drug users
4) recipient of multiple blood infusions
5) commercial sex workers
6) pregnant women
7) testing for STIs
8) sexual assault victims

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4
Q

What are the two diagnosis methods for HIV?

A

serum antibody detection
-Western blot
-enzyme immunoassay

hiv rna detection and quantification (viral load)
-PCR

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5
Q

What are the presentation stages for HIV?

A

1) acute infection
2) asymptomatic
3) persistent generalised lymphadenopathy
4) aids and related infections

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6
Q

What is the clinical presentation of HIV during the acute (primary) infection stage?

A

2-3 weeks of symptoms: fever, malaise, rash, swollen lymph nodes

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7
Q

What is the clinical presentation of HIV during the asymptomatic stage?

A

asymptomatic for many years

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8
Q

What is the clinical presentation of HIV during the persistent generalised lymphadenopathy stage?

A

> 3 months of persistent unexplained lymph node swelling at neck, groin, underarms

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9
Q

What is the clinical presentation of HIV during the AIDs and related conditions stage?

A

AIDS = CD4 < 200/mm3
symptoms of: fever, unexplained weight loss, diarrhoea, swollen lymph nodes
multi-organ involvement
aids defining conditions:
- lymphoma, kaposi sarcoma, pneumocystis pneumonia, aids dementia complex, cytomegalovirus.

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10
Q

what are the primary goals of antiretroviral therapy?

A

Reduce HIV-associated morbidity and mortality
Prolong the duration and quality of survival
Restore and preserve immunologic function
Maximally and durably suppress plasma HIV viral load
Prevent HIV transmission

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11
Q

what are the two surrogate markers for HIV?

A

cd4 and viral load

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12
Q

CD4 surrogate marker useful for?

A

used to measure the
1) subsequent disease progression
2) immune function
3) response to treatment
4) when to START or STOP prophylaxis to opportunistic infections, e.g., pneumocystic pneumonia prophylaxis when cd4 <200/mm3

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13
Q

how often to recheck cd4 after treatment initiation?

A

measure 3-6 months after
every 12 months after adequate

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14
Q

viral load surrogate marker useful for?

A

assessing the response to treatment

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15
Q

how often to check for viral load?

A

2-4 weeks after treatment initiation
6-8 weeks thereafter
(should take 8-24 weeks for viral suppression)

once viral suppression is reached, can be tested every 3-6 months

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16
Q

when to start hiv art?

A

initiate as soon as possible regardless of cd4 count to reduce mortality and morbidity AND prevent HIV transmission

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17
Q

what are the benefits of earlier ART?

A

maintain high cd4 count and potentially irreversible damage to the immune system
decrease risk for hiv associated complications that can occur at cd4+ counts >350/mm3 e.g., TB, non-hodgkin lymphoma, kaposi sarcoma, peripheral neuropathy, hiv associated cognitive impairment
Decreased risk of non-opportunistic conditions, including cardiovascular disease, renal disease, liver disease, and non–AIDS-associated malignancies and infections
Decreased risk of HIV transmission to others, which will have positive public health implications

>350, some of these opportunistic infections MAY occur, so treat ear

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18
Q

what are the LIMITATIONS of earlier ART?

A

Development of treatment-related side effects and toxicities

Development of drug resistance because of incomplete viral suppression, resulting in loss of future treatment options

Transmission of drug-resistant virus in patients who do not maintain full virologic suppression

Less time for the patient to learn about HIV and its treatment and less time to prepare for the need for adherence

Increased total time on medication, with a greater chance of treatment fatigue

Increased cost

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19
Q

factors to consider before starting ART regimen

A

Regimen selection should be individualized and should be based on a number offactors, including:

Patient’s understanding of HIV

Cost and availability

Adherence issues, convenience
pill burden
dosing frequency
food and fluid considerations

Virologic efficacy

Potential adverse effects (comorbidities, drug interactions)

Childbearing potential

Genotypic drug resistance testing 19

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20
Q

what is the life cycle of HIV?

A

free virus -> binding and fusion –> infection –> reverse transcription –> integration –> transcription –> assembly –> budding –> maturation

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21
Q

What are the two recommended ART regimens?

A

2 NRTI + 1 INSTI
- tenofovir + emtricitabine + bictegravir (TEB)
- tenofovir + emtricitabine + dolutegravir (TED)
- abracavir + lamivudine + dolutegravir (ALD)

1 NRTI + 1 INSTI
- tenofovir + dolutegravir

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22
Q

when is dual therapy (INSTI + NRTI) for ART not recommended?

A

1) for patients w/ HIV RNA >500,000 copies/ml
2) HBV coinfection
3) ART to be started before HIV genotypic resistance testing results or HBV testing are available

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23
Q

what are the NRTI drugs?

A

tenofovir (tin of ears)
emtricitabine (electricity bone)
abacavir (abc cadaver)
zidovudine (zombie divin)
lamivudine (lamb voodoo)

24
Q

what are the advantages to using NRTI?

A

renal elimination
little concern for drug interactions

25
Q

what are the disadvantages to using NRTI?
somedrugs are better than others in this class? list the special cases

A

mitochondrial toxicity (rare)
- lactic acidosis and hepatic steatosis (fatty infiltrates)
- lipoatrophy (loss of fat)
zidovudine > others (similar; no emtricitabine)

ALL REQUIRE RENAL DOSE ADJ EXCEPT ABACAVIR

26
Q

what is the adverse effect to using lamivudine

A

Lamivudine –minimal toxicity, nausea/vomiting/diarrhea (N/V/D)

27
Q

what is the adverse effect to using emtricitabine

A

Emtricitabine–minimal toxicities, hyperpigmentation, nausea, diarrhoea

28
Q

what is the adverse effect to using tenofovir

A

Tenofovir: –N/V/D, can cause renal impairment, decrease in bone mineral density

29
Q

what is the adverse effect to using abacavir

A

Abacavir–N/V/D, Hypersensitivity reaction in patients with HLA-B5701. Symptoms incl: rash, fever, rash, malaise or fatigue, loss of appetite, sore throat, cough, shortness of breath. Can be fatal. Discontinue if it occurs, do not rechallenge. Testing for absence of HLA-B5701 is recommended before initiating abacavir.

Concern for association with myocardial infarction –not be used in high cardiovascular risk patients.

30
Q

what is the adverse effect to using zidovudine

A

Zidovudine –N/V/D, myopathy, bone marrow suppression causing anemia or neutropenia.

31
Q

what are the INSTI drugs?

A

bictegravir
dolutegravir
raltegravir
elvitegravir

32
Q

what are the advantages to using INSTI?

A

well tolerated, good virologic efficacy
BD>RE (barrier to genetic resistance)

33
Q

what are the disadvantages to using INSTI? (ADR and DDI)

A

side effects:
- nausea, headache, weight loss, diarrhoea
- psych patients may develop suicidal ideation and depression

ddi:
- BDE are substrates of 3A4
- BA of drugs lowered with concurrent administration polyvalent cations

34
Q

what is the adverse effect to using bictegravir

A

increase serum creatinine (inhibit tubular secretion of creatinine) but no effect on glomerular function

35
Q

what is the adverse effect to using raltegravir

A

increase creatinine kinase (rhabdomyolysis), pyrexia

36
Q

what is the adverse effect to using dolutegravir

A

increase serum creatinine (inhibit tubular secretion of creatinine) but no effect on glomerular function

37
Q

what are the NNRTI drugs?

A

efavirenz
and
rilpivirine

38
Q

what are the advantages to using NNRTI?

A

long half life
less metabolic toxicity (hyperlipidemia, insulin disorder) vs PIs

39
Q

what are the disadvantages to using NNRTI?

A

lower barrier to genetic resistance
cross resistance

skin rash risk, SJS (R < E)
QTC prolongation

40
Q

what is the adverse effect to efavirenz

A

Efavirenz –rash, hyperlipidemia, neuropsychiatric SE(dizziness, depression, insomnia, abnormal dreams,hallucination), increase in LDL-C and triglycerides, hepatotoxicity

41
Q

PK of efavirenz and rilpivirine

A

Efavirenz –CYP 3A4 substrate,
CYP2B6 and 2C19 inducer

Rilpivirine - CYP 3A4 substrate, oral absorption is reduced with increased gastric pH; use with PPIs is contraindicated.

42
Q

what is the adverse effect of rilpivirine

A

Rilpivirine–depression, headache

43
Q

what are the PI drugs?

A

RLAFD
ritonavir
liponavir
atazanavir
darunavir
fosamprenavir

44
Q

what are the advantages to using PI?

A

high genetic barrier to resistance

45
Q

what are the disadvantages to using PI?

A

Metabolic complications (dyslipidemia, insulin resistance)

GI: NVD

Liver toxicity (especially with chronic hepatitis B or C)

CYP3A4 inhibitors and substrates: potential for drug interactions

Fat maldistribution (Lipohypertrophy)

Increased risk of osteopenia/osteoporosis

46
Q

what is the additional properties and adverse effect of ritonavir

A

potent CYP3A4, 2D6 inhibitor; frequently combined with other PI to “boost” their levels (egLopinavir/ritonavir).

Additional SE: paresthesia(numbness of extremities), taste perversion

47
Q

what is the additional properties and adverse effect of darunavir

A

good GI tolerability, less lipids effects.

Additional SE: Skin rash (10%), concern for SJS (it is a sulphonamide)

48
Q

what is the additional properties and adverse effect of atazanavir

A

good GI tolerability, less lipids effects.

Absorption depends on low pH (contraindicated concurrent use with PPIs).

Additional SE: hyperbilirubinemia, prolong QT interval, skin rash

49
Q

what are the fusion inhibitor drugs? include route and freq

A

enfuvirtide IM BD

50
Q

what is the adverse effect of enfuvirtide

A

Injection site reaction (erythema/induration, nodules/cyst, pruritis, ecchymosis in 98%),

rare hypersensitivity reaction reported (fever, rash, chills, decrBP).

Increased bacterial pneumonia.

51
Q

what are the CCR5 antagonist drugs?

A

maraviroc

52
Q

when and how should maraviroc be used?

A

used only in people whose strain of HIV uses the CCR5 receptor to enter the CD4 cells.

Need co-receptor tropism assay before initiation

53
Q

what is the adverse effect of maraviroc

A

ADR-Abdominal pain, cough, dizziness, musculoskeletal symptoms, pyrexia, rash, upper respiratory tract infections, hepatotoxicity, orthostatic hypotension.

cyp3a4

54
Q

what are the strategies to improve adherence to ARTs?

A

Establish readiness to start therapy

Provide education on medication dosing

Review potential side effects

Anticipate and treat side effects

Utilize educational aids including pictures, pillboxes, and calendars

Engage family, friends

Simplify regimens, dosing, and food requirements (taking ARV with or without food)

Utilize team approach with nurses, pharmacists, and peer counselors

Provide accessible, trusting health care team 37

55
Q

which NRTI does not need renal dose adjustment?

A

ABACAVIR

56
Q

which NRTI can be used in pregnancy

A

Zidovudine

57
Q

special properties of ritonavir

A

is used as a pk enhancer along with cobicistat to increase the concentration of ARV (PIs, elvitegravir)
- p450 3a inhibitors

PR3151 (cleefy) (12 decks)

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