HIV: Pathophysiology and Presentation Flashcards
what type of virus is HIV?
retrovirus
- when it makes DNA it uses reverse transcriptase (instead of transcriptase)
2 types of HIV?
HIV-1 = from central/west afrivan chimps, transferred to humans and main cause of infection and global pandemic in 80s
HIV-2 = from west african sootey mangabey, not as significant
main target of HIV?
CD4+ receptors
- glycoprotein found on surface of T helper cells (CD4 cells), dendritic cells, macrophages and microglial cells
what do CD4 T helper cells do?
essential for induction of adaptive immune response
- recognition of MHC2 antigen-presenting cell
- activation of B cells
- activation of cytotoxic T-cells (CD8)
- cytokine release
how does HIV affect immune response?
sequestration of cells in lymphoid tissues
- reduced CD4 cells
reduced proliferation of CD4 cells
reduction of CD8 (cytotoxic) T cell activation
- dysregulated expression of cytokines
- increasing susceptibility to viral infections (including HIV)
reduction in antibody class switching
- reduced affinity of antibodies produced
chronic immune activation (microbial translocation)
effect of reduced immune response?
susceptibility to viral, fungal and mycobacterial infection and infection induced cancers
normal and risky CD4 cell parameters?
normal = 500-1600 cells/mm3
risk of opportunistic infection = <200 cells/mm3
how fast does HIV replicate?
rapid replication in very early and very late infection
new generation every 6-12 hours
how does CD4 cell count and rate of HIV RNA copies made per hour progress?
CD4 count
- drops dramatically over first 6 weeks, then recovers slightly over next few weeks, then declined at a lower rate over following years (asymptomatic infection)
HIV RNA
- increases rapidly up to 6 weeks, then decreases a bit over next 3 weeks, then gradually increase over following years, increase rapidly again over final years of life
initial infection of HIV?
infection of mucosal CD4 cell (langerhans and dendritic cells)
transport to regional lymph nodes
infection established within 3 days of entry
after 3 days, virus disseminates to all tissues
post exposure time window where you can prevent the virus with treatment?
3 days
features of primary HIV infection?
onset 2-4 weeks after infection fever rash (maculopapular) myalgia pharyngitis headache/aseptic meningitis - basically flu like illness very high risk of transmission at this stage
asymptomatic phase of HIV infection?
after primary infection when CD4 cell count has recovered slightly
asymptomatic but not latent
ongoing viral replication and CD4 count depletion
ongoing imune activation
risk of onward transmission if remains undiagnosed
what is the definition of apportunisitic infection?
an infection caused by a pathogen that does not normally produce disease in a health individual
infection only occurs in a weakened immune system
what organism causes pneumocystis pneumonia (PCP)?
pneumocystis jiroveci
CD4 threshold in PCP?
<200
symptoms of PCP?
insidious onset
SOB
dry cough
exercise desaturation (become tachycardic and sats plummet after 5 mins exercise)
CXR findings in PCP?
may be normal
interstitial infiltrates, reticulonodular shadowing
can resemble heart failure more than a pneumonia
diagnosis of PCP?
BAL and immunoflourescence +/- PCR
how is PCP managed?
high dose co-trimoxazole +/- steroid
PCP prophylaxis?
low dose co-trimoxazole
relationship between TB and HIV?
epidemiological synergy
features of TB which are more common in HIV sufferers?
symptomatic primary infection reactivation of latent TB lymphadenopathy miliary TB extrapulmonary TB multi-drug resistant TB immune reconstitution syndrome (immune system wakes up and goes on the attack)
what is cerebral toxoplasmosis?
reactivation of latent infection causing multiple cerebral abscess (chorioretinitis)
what causes cerebral toxoplasmosis?
toxoplasma gondii
in people with CD4 < 150
symptoms of cerebral toxoplasmosis?
headache fever focal neurology seizures reduced consciousness raised ICP
what causes cytomegalovirus in HIV?
reactivation of latent infection in CD4<50
can be retinitis, colitis, oesophagitis
symptoms of CMV in HIV?
reduced visual acuity
floaters
abdo pain
PR bleeding
what skin infections are common in HIV?
herpes zoster (recurrent and multidermatomal)
herpes simplex (extensive, hypertorpic and aciclovir resistant)
HPV (extensive, recalcitrant and dysplastic)
wierd things like penicillosis and histoplasmosis
features of HIV associated neurocognitive impairment?
caused by HIV1 and reduced CD4
causes reduced short term memory +/ motor dysfunction
what is progressive multifocal leukoencephalopathy?
reactivation of latent JC virus (john cunningham virus)
causes rapidly progressing focal neurology and confusion and personality change (in frontal lobe involvement)
occurs when CD4 < 100
other neurological presentations in HIV?
distal sensory polyneuropathy mononeuritis multiplex vascular myelopathy aseptic meningitis GBS viral meningitis cryptococcal meningitis neurosyphilis
what causes wasting in HIV?
metabolic (chronic immune activation)
anorexia
malabsorption/dairrhoea (gut gets leaky)
hypogonadism
AIDS related cancers?
kaposi’s sarcoma
non-hodgkins lymphoma
cervical cancer
how is kaposi’s sarcoma managed?
HAART (if just cutaneous)
local therapies
systemic chemo (if visceral)
features of kaposi’s sarcoma?
- vascular tumour caused by human herpes virus
- can be cutaneous, mucosal or visceral (pulmonary, GI)
features of non-hodgkins lymphoma?
caused by EBV usually more advanced at presentation B symptoms bone marrow involvement extranodal disease increased CNS involvement
how is non-hidgkins lymphoma managed?
same as in non HIV
add HAART
features of cervical cancer?
due to HPV
rapid progression to severe dysplasia and invasive disease
non infectious features of HIV?
mucosal candidiasis (thrush) seborrhoeic dermatitis diarrhoea fatigue worsening psoriasis lymphadenopathy parotitis epidemiologically linked conditions (STIs, hepatitis B/C)
haematological manifestations of HIV?
caused by the HIV virus, infections, AIDs malignancies and HIV drugs and reduced CD4
cause anaemia and thrombocytopaenia (ITP)
modes of transmission of HIV?
sexual transmission (95%) - more common transmission in anal sex, trauma, genital ulceration and concurrent STI
parenteral transmission (IV drug use, blood products, iatrogenic)
mother to child (in utero, delivery or breast feeding)
4 senarios for HIV testing?
universal testing in high prevelence areas (not available in many places)
opt out testing in certian clinical settings (sexual health clinic, drug services etc)
screen high risk groups
test in presence of clinical indicators
where is opt out HIV testing done?
abortion services GUM clinics drug dependency services antenatal services assisted conception services
high risk groups who may be screened?
homosexual men
female partners of bisexual men
IV drug users
people from endemic areas
when is testing done on clinical grounds?
whenever HIV falls within differentials a test should be done regardless of risk factors (e.g psoriasis not getting any better with treatment)
how is consent obtained for HIV test?
explain that theyre being tested for HIV and why
what the benefits of testing are
how and when they get results
reassure confidetiality
process of taking an HIV test in a patient?
document consent or refusal
obtain venous sample for serology
request via ICE (accelerate is clinically indicated)
ensure pathway in place for retrieving and communicating result
process of testing if patient is incapacitated?
only test if in patient’s best interest
consent from relative not needed
if its safe, wait until patient regains capacity
obtain support from HIV team if needed
which HIV markers are used in testing?
viral RNA
antigen (p24)
antibody
how does viral load, p24 and antibody change over time?
viral load and p24 have same pattern but viral load higher
- rapidly increase then decrease over first 3 months
- then very gradually decrease over following years
- then both increase in last years of life
antibody increases very rapidly around 3 month mark, remains high for duration of disease then decreases at end of life
describe 3rd generation HIV antibody test
measures HIV1 and HIV2 antibody
detects IgM and IgG
very sensitive/specific in established infection
20-25 day window period
describe 4th generation HIV test
combined antibody and antigen (p24)
shortens window
variation in quoted window (14-28 days)
significance of window period?
negative test during window period (e.g 4th gen test at 14 days) doesnt rule out infection but negative test at 4 weeks does rule it out
what is POCT?
rapid HIV test
fingerprick blood specimen or saliva
results within 20-30 mins
3rd or 4th generation
advantages of POCT?
simple no lab required no venepuncture needed no anxious wait reduce follow up good sensitivity
disadvantages of POCT?
expensive (£10 per test)
quality control
poor positive predictive value in low prevalence settings
not suitable for high volume or early infection
