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)
