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HIV Flashcards

1
Q

Diarrhoea in HIV, probably going to be…

A

Cryptosporidium
Red cysts in stools- do acid fast staining
Treatment supportive

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2
Q

What factors increase risk of transmission of HIV

A 
Gernital ulceration
High viral load
Not being circumcised in heterosexual transmission
HLA-B concordant couple
Not CCR5 D32 homozygote
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3
Q

What are the main proteins of the virion

A

GP120 is the receptor surface protein
GP41 attaches GP120 to the cell membrane
P24 is core protein around the two ss of RNA

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4
Q

Binding process for HIV?

A 
CD4  binds GP120 
then
 there is coreceptor binding between GP120 and CCR5 or CXCR4
then 
fusion
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5
Q

Where are most of the CD4 cells killed?

A

The gut

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6
Q

What factors affect the rate of disease progression?

A

Coinfection with CMV accelerates
CCR5 using viruses progress faster initially
High HIV neutralising Ab titre slows
Extremes of age are worse
There are intracellular factors that supress replication eg TRIMSalpha, APOBEC3, SAMHDI

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7
Q

What are the five classes of ARV drugs?

A 
Nucleoside/tide RTI
Non nucleoside RTI
Protease inhibitors
Integrase inhibitors
Entry inhibitors
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8
Q

Why do we screen for HLA B5701?

A

To predict occurrence of abacavir hypersensitivity syndrome

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9
Q

Abacavir

A

Nucleoside RTI

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10
Q

Zidovudine

A

Nucleoside RTI

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11
Q

Lamivudine

A

Nucleoside RTI

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12
Q

Emtricitabine

A

Nucleoside RTI

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13
Q

Tenofovir

A

Nucleotide RTI

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14
Q

Efairenz

A

NNRTI

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15
Q

Nevirapine

A

NNRTI

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16
Q

Rilpivirine

A

NNRTI

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17
Q

Raltegravie

A

Integrase Inhibitor

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18
Q

Dolutegravir

A

Integrase inhibitor

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19
Q

Elvitegravir/cobicistat

A

Integrase inhibitor with p450 inhibitor

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20
Q

Lopinavir/Ritonavir

A

Protease inhibitor/P450 inhibitor

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21
Q

Maraviroc

A

Entry inhibitor- CCR5 inhibitor

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22
Q

Virologic supression

A

RNA below detection limit of assay

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23
Q

Virologic failure

A

either incomplete virological response : 24 weeks on ART and RNA over 200

or

virologic rebound: repeated detection of HIV RNA over 200 on several occasions after viral supression

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24
Q

Immunologic failure

A

CD4 drops below baseline on therapy
or
CD4 increase less than 25-50 cells in 12 months

Switching drugs does not work

25
Q

clinical failure

A

HIV related event after three months on therapy, excluding immune reconstitution

26
Q

When is it safe to switch drugs over

A

When viral load undetectable, free to switch one or two

27
Q

When do you do HIV genotype testing

A

Whilst person is taking the failing regimen or has been off for under 4 weeks. Usually need viral load over 1000

Pregnant

New diagnosis, even if not planning to start ART

28
Q

Tenofovir toxicities (3)

A

Fanconi syndrome
Reduce GFR even without fanconi
Reduced BMD

(rare, can still provoke lipoatrophy)

29
Q

Abacavir toxicities (3)

A

3-5% will have an allergic reaction that strongly associated with HLAB5701- may happen any time but often in first 6 weeks of treatment. GI sx, malaise, rash, cough, leukopaenia

Some trials say increase risk MIs but inconsistent

Can still see lipoatrophy but rare

30
Q

Efavirenz toxicities

A

40% CNS- vivid dreams, sleep change, headache

Rash

Teratogenic

Induces AND inhibits

31
Q

Nevirapine toxicities

A

Rash 5-10% usually mild but can be SJS

Enzyme inducer

32
Q

Atazanapine toxicities

A

Hyperbilirubinaemia

Kidney stones

33
Q

Which statin should you use in HIV?

A

Pravastatin has the least P450 interaction but is not very strong

Atorvastatin and Rosuvastatin are suggested but can reach very high levels with protease inhibitors

Avoid simvastatin and lovastatin as –>RHABDO

If TGs are the issue, give gemfibrozil

34
Q

Which protease inhibitors are the best in terms of lipid profile?

A

Darunavir and Atazanavir

35
Q

What is the problem with Nevirapine and methadone?

A

Induces P450 so can cause methadone withdrawl if started

36
Q

Which agents have minimal/minor P450 activity?

A

Raltegrivir and Dolutegravir have minor P450 activity

37
Q

Inhaled steroids and HIV treatment?

A

Inhaled fluticasone (not beclamethasone) can cause cushings, AVN, osteoporosis in setting of P450 3A4 inhibition

38
Q

In general, protease inhibitors do what with drug metabolism?

A

CYP 3A4 inhibitors

PIs (in order of potency:
ritonavir, indinavir, nelfinavir,
amprenavir, atazanavir,
saquinavir)

39
Q

Which ART drugs are CYP 3A4 inducers?

A

efavirenz

nevirapine,

40
Q

CD4 count 200-500 : what infections are you worried about?

A

HSV
Pneumococcal pneumonia
Oral candida
TB

41
Q

CD4 50-200 : what infections are you worried about?

A

PCP plus cancers plus brain things

PCP
CNS toxoplasmosis
cryptococcus
K's sarcoma
NHL
Primary CNS lymphoma
42
Q

Under 50 CD4 cells: what infections are you worried about?

A

disseminated MAC
CMV retinitis
Cryptosporidiosis

43
Q

What are the strong indications to start ART?

A 
history of aids defining illness
CD4 under 500
Any CD4 and pregnancy
Any CD4 and HBV needing treatment
HIV associated nephropathy
44
Q

What is immune restoration disease?

A

Worsening symptoms of previously diagnosed opportunistic infection (paradoxical IRD), or new opportunistic infection (unmasking IRD).

Due to enhanced immune recognition of intercurrent pathogens/antigens

45
Q

If someone presents with an opportunistic infection and not on ART…when to start?

A

Treat OI and start ART 2-4 weeks later in general TO PREVENT OVERLAP TOXICITY
TB and cell count over 50- do not start for 4-8 weeks TO MINIMISE IRIS
TB and CD4 under 50- 2-4 weeks TB tx TO MINIMISE AIDS PROGRESSION AND DEATH

46
Q

Treatment for cerebral toxoplasmosis?

A

Sulfadiazine and pyrimethamine

47
Q

Zidovudine toxicities? (3)

A

MYOPATHY
black nails
anaemia

48
Q

Early after HIV probably caught, what can you test?

A

p24 Ag

49
Q

What proportion of people with abacavir hypersensitivity have HLA B5701 compared with people who can tolerate abacavir?

A

78% vs 2%

50
Q

Which ART gives you nephrolithiasis?

A

Indinavir

51
Q

How does a Jarich-Herxheimer reaction occur?

A

Release of endotoxins with first dose of abx- within a few hours see rash, fever, tachy

52
Q

what happens with HIV affecting cells in infectionq

A

impaired production CD34 progenitor cells in BM
reduce proliferation thymocytes–>reduced naive CD4
direct infection memory CD4 but low frequency
depletion of mucosal CD4 by infection of dendritic, macrophages, CCR5 positive and negative cells
hihg levels of immune activation that increase proliferation and death of both CD4 and 8 cells
T cells are retained in the LN

53
Q

How does aspergillus cause cancer!?

A

aflatoxins produced which are assoc with high rates of p53 mutation and HCC

54
Q

What does zidovudine myelopathy look like

A

proximal muscle weakness and tenderness

55
Q

CMV vs HIV myelopathy

A

CMV get CSF PCR and neutrophilic pleocytosis
HIV myelop looks similar but CSF ok- degen posterior and lateral spinal cord tracts

HIV dementia- fine motor, urine incontinence

56
Q

Which drug causes pancreatitis?

A

Didanosine

57
Q

Nevirapine feared side effect?

A

SJS

58
Q

Lipoatrophy worst

A

NRTIs thymidine analogue

-zidovudine and stavudine

59
Q

How do you judge successful treatment of syphilis?

A

RPR and VDRL falls 4 fold in 6-12 months
=cure

treat contacts within last 3 months empirically as serology might not be positive yet

ID (14 decks)

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