HIV Flashcards
(70 cards)
1
Q
What does ‘natural history of HIV infection’ mean?
hallmark of disease progression
A
The course of the disease process in the absence of tx
- CD4+ T cell depletion
- cellular immunity impairment
- susceptibility to opportunistic infections
2
Q
HIV enter and time to spread across body
A
Retrovirus of lentivirus family
virus particles enter via genital mucosa/directly into bloodstream -> to lymph nodes in CD4+ T cells -> body spread in 3-5 days
3
Q
HIV viral replication cycle
A
- binding = CD4+ T cells, CD4 molecules, co-receptors (CCR5/CXCR4). CD4 also on monocytes/macrophages, DCs, eosinophils, microglial cells
- fusion
- reverse transcription
- integration
- protein synthesis, processing and assembly
- budding
4
Q
three issues with HIV
A
Destruction of infected CD4+ T cells
- early in infection -> regeneration and re-establishes -> immune function preserved for many years
- chronic immune activation, immune dysregulation, ongoing direct viral killing of CD4 cells -> CD4 cells gradual decline -> fall below threshold -> opportunistic infections occur
Rapid HIV mutation
- new generation every 1.5 days
- no proof-reading mechanism so mutation very quick
- -> genetical diverse virus pool, some evade detection by the immun system
Reservoirs of latent infection
- HIV replication requires CD4+ cell activation
- some CD4+ cells infection with HIV are resting, and persist as latently infected cells if they are not killed
- even with viral replication is suppressed by antiretroviral drugs, this infection reservoir persists for many years -> why HIV infection cannot be eradicated with current tx
5
Q
3 clincial stages of HIV infection: primary/acute infection
A
- primary/acute infection
- asymptomatic chronic infection
- symptomatic disease, including AIDS
Primary infection
- 1-4 wks after virus inquisition until production of sufficient HIV antibodies to be detected by an HIV antibody test
- sx’s 40-90% individuals, lasts 7-10 days = fever, malaise, arthralgia, loss of appetite, rash, myalgia, pharyngitis, oral ulcers, weight loss >2.5 kgs aka anorexia
- neuro sx (high viral loads in CSF) = headache, menignism (photphobia, neck stiffness/nuchal rigidity, seizures, kernigs and brudzinksi’s sign), CN palsies, transient hemiplegia/dysarthria
- DDx = often missed (ddx infectious mononucleosis/EBV/VMW, influenza, malaria, acute hep B/C, 2o syphilis, rubella, drug reaction e.g. to ART in PEP for HIV), always consider when presentation is unexplained fever,
- Dx = clincial suspicion, p24 antigen or viral load
- viral load = 100 million RNA copies per ml of blood, massive CD4+ depletion in gut-associated lymphoid tissue, CD4+ count in seurm may fall, high viral load in blood and genital fluids increases the risk of onwards transmission
*
6
Q
- asymptomatic chronic disease
A
Lasts 5-10 years
HIV viral load falls and then plateaus
stable HIV viral load ‘set point’ = rises as ‘AIDS’ develops
CD4 count usually recovered but not usually to baseline levels
- STILL functional deficiencies in CD4+ T cell responses
CD4 count gradually falls overt ime
7
Q
Symptomatic disease progression
A
First manifestions
- frequent minor infections e.g. viral infections, recurrent vaginal/oral candidiasis (agular cheilitis sign around mouth in candida)
- derm (dry skin, seborrhoeic dermatitis, psoriasis)
- haem (anaemia, thrombocytopaenia)
- systemic (fatigue, weight loss, night sweats, diarrheoa)
unusual infections
- oral hairy leukoplakia
- multidermatomal shingles
AIDS-defining syndromes, infections and malignancies (represents severe immunosuppresion)
- rare above CD4 >200
- CMV retinits unusual until CD4<50
- candidiasis of oes, bronchi, trachea, or lungs
- herpes simplex of oes, bronchi, trachea, or lungs
- cryptococcosis
- cytomegalovirus disease
- HIV encephalopathy
- Kaposi’s sarcoma (HHV8, KSHV)
- Lymphoma: Burhkitt’s, immunoblastic, primary cerebral
- Mycobacterium avium complex, TB, or other species
- PCP
- Progressive multifocal leukoencephalopathy (JC virus)
- toxoplasmosis, cerbral
8
Q
Opportunistic and not opportunistic infections
A
9
Q
malignancies associated with viral infections
A
10
Q
the role of HIV in non-AIDS-defining clinical disease
A
renal
- post-infectious glomerulonephritis
- HIV-associated neuropathy (HIVAN) = more common in black ethnic groups, men and injecting drug users
cardiovascular
- increased rates of atherosclerosis
- HIV-associated dilated cardiomyopathy
- pericarditis and pericardial effusions
- pulmonary hypertension
hepatic
- fast progression of cirrhosis in those with Hep B and C infection
- higher rate sof NASH
bone
- ostopaenia, osteoporosis
- high rates of vit D deficiency and osteomalacia
- osteonecrosis
neuro
- peripheral neuropathy
- bell’s palsy
- mononeuritis multiplex
- vauolar myelopathy
- cognitive impairment
11
Q
LTNPs
A
long term non-progressors 5% of HIV patients = maintain low viral laods and good CD4 counts over many years (over 20 years in some cases)
12
Q
Disease progression = host and viral factors
A
Disease progression is faster in those who have a symptomatic primary infection, particularly in those who have a severe and prolonged seroconversion illness.
Host factors
- CCR5 (good), HLA I alleles (B27, B57)
- CD8+ HIV-specific TY cells destory HIV-infected CD4+ cells by MHC I-restricted cytolysis/indirectly via cytokines and chemokines. Host cellular transcription factors.
Viral fitness
- HIV mutations that = evolve to evade the immune response, develop under pressure of AR’s (and confer drug resistance)
13
Q
life expectancy
A
variable
atients in Europe and North America who start antiretroviral therapy and whose CD4 counts rise to above 350 at 1 year after treatment initiation have an estimated life expectancy approaching that of the general populatiom
Recent improvements in survival with HIV probably reflect transition to less toxic antiretroviral drugs, improved adherence, prophylactic measures, and management of comorbidity
14
Q
HIV-2
A
1 = from chimpanzee
2 = sooty mangabey monkeys in West Africa (spread to Portugal and their former colonies)
- less transmissible, less pathogenic
- viral loads lower
- disease progression is slower
15
Q
routine monitoring of people living with HIV
A
All HIV+ adults
Pre-ART initiation
Immediately post-ART initiation
Established ART
Not current wanting ART
16
Q
HIV hx
A
17
Q
sexual hx in HIV
A
- unprotected sex in last 72 hours (vaginal/anal) -> to offer post-exposure prophylaxis to partners
- hx from all sexual partners since the last negative HIV test, or lifetime aprtners if never tested before -> contacted and offered testing
- advice on safer sex, contraception and pre-conception (try to conceive with least risk to their partner)
- women not on ART/without an undetectable viral load -> self-insemination
- men not on ART/without an undetectable viral load -> fertility clinics to arrange sperm washing
18
Q
HIV physical exam
A
general = skin, oropharynx, lymph nodes, heart, lungs, abdominal (hepatosplenomegaly), MSK, neuro, anogenital, cognitie function testing
measure weight, height, BMI, waist circumference, BP
In CD4 <50/ul = dilated fundoscopy or retinal photography to look for CMV retinitis
19
Q
HIV Ix’s
A
- HIV-1/2 status = serology, HIV avidity assays
- CD4 cell count and CD4% =
- HIV viral load = measure RNA in plasma (time since last test, known time of exposure, sx of seroconversion illness, test for 1o HIV infection, CD4 count). Steady state after around 4 months
- resistance and HLA-B*57:01 testing = HLA one for Abacavir therapy as +ve can mean abacavir hypersensitivity reaction
- biochemistry and haematology = metabolic problems (insulin resistance, lipid dysregulation, renal/liver/bone/disease) -> renal/liver/bone profile, HbA1c, dipstick urinalysis + urine protein/creatinine ratio if dipstick +ve for protein, FBC
- other infections and immunity = hep B and C serology, immunity to hep A/measles/varicella, full STI screen including syphilis serology, IGRA
- women = cervical cytology 25-65 (and not done in last 12 months), rubella immunity in women of child-bearing age
- over 40s = QRISK2, FRAX tool (over 50s)
20
Q
routine monitoring for HIV+ not on ART
A
21
Q
pre-ART routine monitoring
A
22
Q
immediately post-ART routine monitoring
A
23
Q
established ART routine monitoring
A
hx:
- adherence to ART
- medications
- contraception and plans for conception
- symptoms
24
Q
what things should you consider on top of routine monitoring
A
25
test recommended in all new HIV diagnosis
26
routine monitoring summary
27
ituations where ART should be commenced regardless of CD4 if ART at all CD4 is not commissioned routinely:
AIDs event
Non-AIDS conditions (HIV associated neprhopathy, peripheral neuropathy, chronic fatigue, non-AIDS malignancies requirign chemotherapy or radiotherapy)
PHI
OFFERED TO ALL = prevention of onward transmission
Hep B or C co-infection
28
PHI
HIV infection within max 6 months from estimated time of HIV transmsision
\>100k viral load copies/mL
ART for PHI criteria:
* neuro involvement
* any AIDs-defining illness
* PHI diagnosed within 12 weeks of a previous -ve test
29
ART first line + alternatives, and third agents
truvada (prefered) = truvada and emctricitabine
Kivexa (alternative) = abacavir and lamivudine
3rd agents = NNRTI, integrase inhibitors, protease inhibitors
* NNRTI low risk GI side effects/low pill burdens
30
efavirenz side effects
psychiatric effects including dizziness, abnormal dreams and insomnia, typically more pronounced in the first 1-2 weeks of treatment. Some patients report significant levels of side effects which persist beyond this induction period, necessitating switching off efavirenz.
used with caution in patients with current or previous history of psychiatric disorders, including depression, anxiety and suicidal ideation.
31
comparing PIs, NNRTIs, INIs
32
most important adverse effect of abacavir
symptoms of this
T3 MHC I Hypersensitivity reaction (HSR). This syndrome consists of multisystem presentation, usually 1-4 weeks after starting abacavir.
Symptoms are fever, rash, abdominal pain, cough, shortness of breath and hypotension. Often symptoms are mild when they start but, with each dose, escalation in severity occurs. The most serious problems, including shock and death, occur in those who continue treatment despite the development of hypersensitivity, or in those who stop the drug and are then challenged with abacavir.
33
other abacavir issues
abacavir use and increased risk of cardiovascular disease
* most significant in those patients who already have a moderate to high cardiovascular risk.
commencing abacavir based combinations in patients with high viral loads (\>100 000 copies/ml)
34
Tenofovir disoproxil fumarate (TDF) side effects
TDF may be associated with a small decline in estimated glomerular filtration rate (eGFR)
* renal monitoring (eGFR and proteinuria
small drope in BMD
35
3rd agents
36
which genotype resistance to medication is not really tested?
integrase
37
co-infections and co-morbidites and lifestyle for use of ARVs in different patient groups
co-infections = hep b and c
co-morbidities = tenofovir df (pre-existing renal disease, bmd), efavirenz (psych)
38
virologicals suppression definition
VL level \<50 copies/ml is achieved and maintained
Durable and maximal plasma viral load (VL) suppression \<50 copies/ml (Fig 1) is the desired outcome in both antiretroviral-naïve and experienced patients. This is 'undetectable', i.e. below the limit of assay detection. In newer assays, 'undetectable' may be lower (e.g. \<20 copies/ml)
Treatment failure should be identified and managed promptly in order to achieve this outcome
39
3 types of ARV tx failure
virological failure
* incomplete virological response after commencing treatment or evidence of confirmed virological rebound (as defined below)
incomplete virological response
* Two consecutive VL \>200 copies/mL after 24 weeks without ever achieving VL \<50 copies/mL
virological rebound
* failure to maintain a VL below the limit of detection (ordinarily \<40–50 copies/mL) on two or more consecutive occasions
* Patients who are developing virological rebound would show further increases in viral load on subsequent testing whereas those with a viral blip should revert back to undetectable.
40
LLV
persistent VL between 50-200 copies/ml (Fig 1)
When compared to virological suppression (\<50 copies/ml), LLV is associated with an increased risk of virological failure and resistance.
41
switching a failing treatment regimen:
42
SBA
43
What will be the effect of administering a drug which is a substrate for hepatic enzymes together with an inhibitor?
This will reduce not only the clearance of the drug but also the variability of the exposure. This might alter the frequency of dosing recommended.
44
enzyme inducers and inhibitors for ARVS
45
Natural history of HIV
normal = 500-1500
late presenter = \<350 cd4
advanced status = \<200 OR AIDS-defining condition
46
HIV infection time
47
Skin and mucosal infections
Bacterial
* folliculitis
* abscesses
* impetigo
Fungal
* seborrhoeic ermatitis
* candidiasis
viral
* cold sores (HSV)
* shingles (VZV)
* oral hairy leukoplakia (EBV)
* molluscum (poxvirus)
* warts (HPV)
48
VZV (herpes zoster virus/chickenpox)
herpes zoster reaction frequent immunodeficiency
can present in more than one dermatome
dx clinical/PCR (VZV DNA)
49
Herpes simplex virus 1 and 2
more severe in persistent in HIV+ with advanced disease
chronic ulcers (\>1 month) or bronchitis, pneumonitis, or oesophitis = AIDS-defining
Lesions can be atypical/superinfected
Dx clinical/ PCR (HSV DNA)
50
Kaposi Sarcoma
cancer of blood vessels associated with HHV8
purplish-red oval-shaped pathces which become raised
AIDS-defining
can affect internal organs (visceral KS)
* oral lesions are proxy for enteric lesions
* Dx histopathology
Dx clinical/histology
51
Candida albicans
oesophageal = AIDS-defining
painful swallowing -\> can lead to severe wasting
Dx clinical/OGD/microscopuy
52
CMV ('big cell')
CD4 \<50/mcl
AID-defining
**colitis/oesophagitis: bloody diarrhoea, dysphagia**
Dx: endoscopies/histopathology (nuclear inclusion bodies)/CMV PCR (serum/tissue)
53
Cryptosporidiosis, microsporidiosis, cyystoisopsoriasis
CD4 \<50/mcl
persistent disease, watery diarrhoea, malabsorption, weight loss
Dx stool microscopy (special stains)/histology
54
Non-tubercular mycobacteria
MAC
patients with CD4+ \<50
disseminate, multi-organ infection with hepatosplenomegaly, lymphadenopathy and laboratory abnormalities, often GUT involvement
fever, night sweats, weight loss, fatigue, diarrhoea, and abdominal pain
Dx microbiology (AFBs smear/culture + PCR, blood cultures) and histopathology
55
Wasting syndrome
involuntary loss of more than 10% of body weight + at least 30 days of either diarrhoea or weakness and fever
AIDS-defining
chronic inflammation, mucosal alteration and bacterial translocation
56
PJP
fungla infection
progressive SoB and fatigue
AIDS defining
Dx = clinical (desaturation at exertion), imaging, micro-PCR (pJP DNA and BDGlucan serum/induced sputum/BAL)
57
TB in advanced HIV
CD4 \<200 -\> atypical presentation
lower/middle lobe infiltrates, disseminate TB, intrathoracic adenopathy
feveer, cough, sweats, weight loss
Dx micro (sputum AFB + culture, TB PCR, histopathology)
58
Neurotoxoplasmosis
commonest cause of mass lesions in immcomp HIV+
reactivtion of toxoplasma gondii cysts (protozoa)
headaches, personality changes, altered mental status, seizures, hemiparesis/focal weakness
Dx = imaging (CT/MRI), LP, toxoplasma serology, brain biopsy (gold definitive standard)
empiric tx with re-assessment at 2 wks
59
progressive multifocal leukocencephalopathy
demyleinating disease of CNS 2o to JC Virus
insidious onset and steady progression of focal sx: behavioural, speech, cognitive, motor and visual impairment
Dx MRI (asymmetric, subcortical, focal changes)/CSF (JCV DNA+)
no specific tx
poor prognosis
60
primary cerebral lymphoma
rare
cd4+ \<50
EBV+ associated
extremely poor prognosis
Dx imaging, CSF (EBV DNA++), histopathology
61
cryptococcal meningitis
fungal disease, **cryptococcus neoformans** = ubiquitous yeast
most common menigitis in areas with high HIV prevalence
in severe hiv+ immsup cd4\<50
subacute menginitis (headache, fever, photophobia, increased ICP), meningism often abset
raised ICP -\> therapeutic LPs
Dx = CSF (cryptococcal antigen+ culture)
serious condition
62
TB meningitis and tuberculomas
HIV+ increased risk of extrapulmonary disease, including meningitis and CNS tuberculomas
meningitis can present acutely/subacutely/chronically (altered level of consciousness)
Dx = CSF (AFB culture, PCR), lymphocytic pleocytosis, highproteins, low CSF glucose (disproportionate to cellularity in CSF), imaging (MRI - enhancement of meningitis, basal +++)
poor prognosis, high mortality
63
CMV NS infection and retinitis
ventriculitis/encephalitis
myelitis
polyradiculopathy
retinitis = perivasucular haemorrhage
Dx = imaging (MRI), CMV DNA (blood/CSF)
64
HIV encephalopathy and dementia
2o to ongoing, uncontrolled viral replication in brain, CD4\<200
ADC (AIDS Dementia Complex) = cognitive, motor, behavioural features
prognosis is poor without ARVs = response to tx varies
65
AIDS-related lymphomas
NHL of high grade B cell
* systemic NHL(DLBCL, plasmabalstic,Burkitt)
* priamry CNS lymphomas
* primary effusion (body cavity) lymphoma
many related EBV+ infection
**B-symptoms (weight loss, fevers, sweats), lymphadenopathy, hepatosplenomegaly**
Dx clincial, imaging (CT and PET), histopathology
66
Invasive cervical cancer
most common cancer in women living with HIV
presents at younger age, HPV+ associated
risk icnreased with decrease in CD4+
Dx cervical smear, colposcopy
preventable and curable if diagnosed and treated early
(HPV vaccine, regular bscreening)
67
Why diagnose the undiagnosed?
higher rates of transmission
increased complications
increased cost to health service
68
BHIVA/BASHH/BIA UK National Guidelines for HIV Testing
1. **targeted screening**: risk groups
2. **targeted screening:** indicator diseases
3. **routine screening in general medical settings** when local diagnosed HIV prevalence \>0.2%
69
HIV testing
HIV testing is the gateway to HIV tx and HIV prevention
Any trained healthcare worker can offer an HIV test
NO need for lengthy pre-test discussion
It is ALWAYS in person's best interest to know their HIV status
Explain:
* risk vs benefit
* what the various results mean
* how the patient will receive their results
* understand the window period
70
HIV tests
HIV tests usually test for immune responses to HIV (antibodies)
samples may be whole blood, capillary blood (fingerprick) or oral fluid
some tests (4th and 5th generation) may test for components of the virus itself
after infection, it may take some time for both the virus and latterly the antibodies, to be reliably detected - the 'window peiod'
a 4th/5th generation blood test has a window period of 45 days
