HIV Flashcards
what does HIV use to bind to CD4?
gp120 initial binding
gp41 confromational change
what co-receptors does HIV bind to, to allow entry to the CD4+ cell?
CCR5
CXCR4
which protein provides intrastructural support to HIV?
Gag protein
Innate response to HIV involves:
non-specific activation of macrophages, NK cells, and complement
stimulation of dendritic cells via TLR
release of cytokines and chemokines
Adaptive response: neutralising abs
anti-gp120, anti-gp41
Adaptive response: non-neutralising abs
anti-p24
anti-Gag
chemokines produced by CD8+ to prevent HIV entry into cells
RANTES
MiP a/b
Mechanisms by which HIV damages immune response
- not neutralised by abs
- kills CD4 cells, or causes them to be killed by CTLs leading to failure of Ig/CD4 memory formation and signalling to continue immune response
- loss of interactions with CD8, monocytes, dendritic cells, B cells
- infected monocytes and dendritic cells are also killed so there is no means of presenting antigens, therefore no memory
- variation and mutation
Main test used in screening for HIV
ELISA ab test - looks for antibodies in the serum to HIV
other tests for HIV - useful if screening is positive
- antigen-ab tests: Western blot, looks for p24 viral capsid protein, and HIV-ab
- being fast superseded by NAATs - looks for HIV viral RNA/DNA in the blood - can be positive 7-28 days after infection. Used in high risk pts and in pts with early sx
How long does it take for a person to seroconvert (making HIV-abs - positive ELISA)
3-12 weeks, on avg 10 weeks post infection
tests not positive before this (3m)
2 tests used in monitoring HIV
1) viral load - via PCR
2) CD4+ count
Two methods of resistance testing in antiretroviral use
- Phenotypic: viral replication is measured in cell cultures under increasing amounts of antiretrovirals. compared to wild type.
- Genotypic: mutations are determined by direct sequencing, compared to wild type.
When to start treatment in HIV
CD4<350
OR symptomatic
HAART antiretroviral therapy usually consists of:
2 NNRTI
+ 1 PI/NRTI
ART in pregnancy
Zidovudine:
- antepartum PO
- delivery IV
ART in newborns born to HIV+ mothers
Zidovudine 6 weeks PO
reduces transmission from 26% to 8%
Raltegravir, Elvitegravir
GRAvir = InteGRAtion inhibitors
Ritonavir, Indinavir, Nelfinavir, Atazanavir, Amprenavir
NAVIR = Protease inhibitors
Enfuvirtide
Fusion inhibitor
enFU
Tenofovir, Abacavir, Trizirvir, Zidovudine, Lamivudine
NRTI
Targets for NRTI/NNRTI
Reverse transcriptase - interrupt transcription of viral DNA
Target for fusion inhibitors
gp120/gp41
tagets for protease inhibitors
viral Protease - prevent release and budding of viral proteins
Targets for integrase inhibitors
viral Integrase - prevent viral DNA being inserted into host DNA.
