HIV Flashcards
Diarrhoea in HIV, probably going to be…
Cryptosporidium
Red cysts in stools- do acid fast staining
Treatment supportive
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
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
Binding process for HIV?
CD4 binds GP120 then there is coreceptor binding between GP120 and CCR5 or CXCR4 then fusion
Where are most of the CD4 cells killed?
The gut
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
What are the five classes of ARV drugs?
Nucleoside/tide RTI Non nucleoside RTI Protease inhibitors Integrase inhibitors Entry inhibitors
Why do we screen for HLA B5701?
To predict occurrence of abacavir hypersensitivity syndrome
Abacavir
Nucleoside RTI
Zidovudine
Nucleoside RTI
Lamivudine
Nucleoside RTI
Emtricitabine
Nucleoside RTI
Tenofovir
Nucleotide RTI
Efairenz
NNRTI
Nevirapine
NNRTI
Rilpivirine
NNRTI
Raltegravie
Integrase Inhibitor
Dolutegravir
Integrase inhibitor
Elvitegravir/cobicistat
Integrase inhibitor with p450 inhibitor
Lopinavir/Ritonavir
Protease inhibitor/P450 inhibitor
Maraviroc
Entry inhibitor- CCR5 inhibitor
Virologic supression
RNA below detection limit of assay
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
Immunologic failure
CD4 drops below baseline on therapy
or
CD4 increase less than 25-50 cells in 12 months
Switching drugs does not work
clinical failure
HIV related event after three months on therapy, excluding immune reconstitution
When is it safe to switch drugs over
When viral load undetectable, free to switch one or two
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
Tenofovir toxicities (3)
Fanconi syndrome
Reduce GFR even without fanconi
Reduced BMD
(rare, can still provoke lipoatrophy)
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
Efavirenz toxicities
40% CNS- vivid dreams, sleep change, headache
Rash
Teratogenic
Induces AND inhibits
Nevirapine toxicities
Rash 5-10% usually mild but can be SJS
Enzyme inducer
Atazanapine toxicities
Hyperbilirubinaemia
Kidney stones
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
Which protease inhibitors are the best in terms of lipid profile?
Darunavir and Atazanavir
What is the problem with Nevirapine and methadone?
Induces P450 so can cause methadone withdrawl if started
Which agents have minimal/minor P450 activity?
Raltegrivir and Dolutegravir have minor P450 activity
Inhaled steroids and HIV treatment?
Inhaled fluticasone (not beclamethasone) can cause cushings, AVN, osteoporosis in setting of P450 3A4 inhibition
In general, protease inhibitors do what with drug metabolism?
CYP 3A4 inhibitors
PIs (in order of potency:
ritonavir, indinavir, nelfinavir,
amprenavir, atazanavir,
saquinavir)
Which ART drugs are CYP 3A4 inducers?
efavirenz
nevirapine,
CD4 count 200-500 : what infections are you worried about?
HSV
Pneumococcal pneumonia
Oral candida
TB
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
Under 50 CD4 cells: what infections are you worried about?
disseminated MAC
CMV retinitis
Cryptosporidiosis
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
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
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
Treatment for cerebral toxoplasmosis?
Sulfadiazine and pyrimethamine
Zidovudine toxicities? (3)
MYOPATHY
black nails
anaemia
Early after HIV probably caught, what can you test?
p24 Ag
What proportion of people with abacavir hypersensitivity have HLA B5701 compared with people who can tolerate abacavir?
78% vs 2%
Which ART gives you nephrolithiasis?
Indinavir
How does a Jarich-Herxheimer reaction occur?
Release of endotoxins with first dose of abx- within a few hours see rash, fever, tachy
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
How does aspergillus cause cancer!?
aflatoxins produced which are assoc with high rates of p53 mutation and HCC
What does zidovudine myelopathy look like
proximal muscle weakness and tenderness
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
Which drug causes pancreatitis?
Didanosine
Nevirapine feared side effect?
SJS
Lipoatrophy worst
NRTIs thymidine analogue
-zidovudine and stavudine
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
