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Flashcards in HIV Deck (59)
1

Diarrhoea in HIV, probably going to be...

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

2

What factors increase risk of transmission of HIV

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

3

What are the main proteins of the virion

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

4

Binding process for HIV?

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

5

Where are most of the CD4 cells killed?

The gut

6

What factors affect the rate of disease progression?

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

7

What are the five classes of ARV drugs?

Nucleoside/tide RTI
Non nucleoside RTI
Protease inhibitors
Integrase inhibitors
Entry inhibitors

8

Why do we screen for HLA B5701?

To predict occurrence of abacavir hypersensitivity syndrome

9

Abacavir

Nucleoside RTI

10

Zidovudine

Nucleoside RTI

11

Lamivudine

Nucleoside RTI

12

Emtricitabine

Nucleoside RTI

13

Tenofovir

Nucleotide RTI

14

Efairenz

NNRTI

15

Nevirapine

NNRTI

16

Rilpivirine

NNRTI

17

Raltegravie

Integrase Inhibitor

18

Dolutegravir

Integrase inhibitor

19

Elvitegravir/cobicistat

Integrase inhibitor with p450 inhibitor

20

Lopinavir/Ritonavir

Protease inhibitor/P450 inhibitor

21

Maraviroc

Entry inhibitor- CCR5 inhibitor

22

Virologic supression

RNA below detection limit of assay

23

Virologic failure

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

24

Immunologic failure

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

Switching drugs does not work

25

clinical failure

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

26

When is it safe to switch drugs over

When viral load undetectable, free to switch one or two

27

When do you do HIV genotype testing

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

Tenofovir toxicities (3)

Fanconi syndrome
Reduce GFR even without fanconi
Reduced BMD

(rare, can still provoke lipoatrophy)

29

Abacavir toxicities (3)

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

Efavirenz toxicities

40% CNS- vivid dreams, sleep change, headache

Rash

Teratogenic

Induces AND inhibits

31

Nevirapine toxicities

Rash 5-10% usually mild but can be SJS
Enzyme inducer

32

Atazanapine toxicities

Hyperbilirubinaemia
Kidney stones

33

Which statin should you use in HIV?

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

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

Darunavir and Atazanavir

35

What is the problem with Nevirapine and methadone?

Induces P450 so can cause methadone withdrawl if started

36

Which agents have minimal/minor P450 activity?

Raltegrivir and Dolutegravir have minor P450 activity

37

Inhaled steroids and HIV treatment?

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

38

In general, protease inhibitors do what with drug metabolism?

CYP 3A4 inhibitors

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

39

Which ART drugs are CYP 3A4 inducers?

efavirenz
nevirapine,

40

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

HSV
Pneumococcal pneumonia
Oral candida
TB

41

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

PCP plus cancers plus brain things

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

42

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

disseminated MAC
CMV retinitis
Cryptosporidiosis

43

What are the strong indications to start ART?

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

44

What is immune restoration disease?

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

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

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

Treatment for cerebral toxoplasmosis?

Sulfadiazine and pyrimethamine

47

Zidovudine toxicities? (3)

MYOPATHY
black nails
anaemia

48

Early after HIV probably caught, what can you test?

p24 Ag

49

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

78% vs 2%

50

Which ART gives you nephrolithiasis?

Indinavir

51

How does a Jarich-Herxheimer reaction occur?

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

52

what happens with HIV affecting cells in infectionq

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

How does aspergillus cause cancer!?

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

54

What does zidovudine myelopathy look like

proximal muscle weakness and tenderness

55

CMV vs HIV myelopathy

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

Which drug causes pancreatitis?

Didanosine

57

Nevirapine feared side effect?

SJS

58

Lipoatrophy worst

NRTIs thymidine analogue

-zidovudine and stavudine

59

How do you judge successful treatment of syphilis?

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