I - HIV Flashcards
How many people have AIDS worldwide
37 million
How many ppl have died of aids
39 million
How is HIV transmitted
Sexual
Infected blood
Vertical - mother to child
What type of virus is HIV
RNA retrovirus
What type of cell does HIV target as a host
Cd4 t helper cells mainly
Also cd4+ monocytes and dendritic cells
How does HIV replicate in host cell
Reverse transcriptase converts RNA to DNA to integrate in host genes
What is the receptor for HIV
Cd4 molecule
How does the virus bind to cd4+ cells (2 steps)
Gp120 - initial binding
Gp41 - conformational change
What coreceptors are used by hiv to bind to cd4 cells and on what cells are the found
Ccr5 and cxcr4 chemokine receptors (on macrophages)
What protein is the intrastructural support for HIV
Gag protein
Describe innate response to HIV
Activation of macrophages, nk cells and complement
Stimulation of dendritic cells via TLR
Release of cytokines and chemokines
Describe adaptive response to hiv
Neutralising & non neutralising ABs
Cd8+ T cells prevent HIV entry via chemokine production
Neutralising ABs to HIV
anti gp120 and anti gp41
Non neutralising AB to HIV
anti p24 gag IgG
What chemokines do cd8+ T cells produce to prevent hiv entry
Mip-1a
Mip-1b
RANTES
How does HIV damage the immune response
Activated infected cd4+ helper T cells are killed by cd8+ T cells / are anergised (disabled)
—> cd4 T cell memory lost and can’t activate memory cytotoxic T lymphs —> monocytes / dendritic cells not activated by cd4+ cells —> can’t prime naive cd8+ cyctoxic T lymphs
How does reverse transcriptase helps HIV evade immune response
It is error prone, so quasi species are produced which escape detection
Is HIV infectious when AB coated
YES
What are 2 key ingredients for effective HIV immunity
ABs to prevent infection and neutralise virus
Sufficient cytotoxic T lymphs to eliminate latent infected cells
Median time from HIV infection to AIDS
8 to 10 years
What is the median time from HIV infection to AIDS in rapid progressions
2-3 years
What are long term non progressors of HIV
Stable cd4 count and no symptoms after 10 years
% of HIV patients who are rapid progressors ? Long term non progressors ?
Rapid 10%
Long term non <5%
What predicts disease progression in HIV
initial viral burden
How is HIV screened for
ELISA detects anti HIV ABs
How is HIV diagnosed
Western blot to detect AB
How long does it take after infection for a person to test positive for HIV via western blot & why
10 weeks
- western blot requires patient to have SEROCONVERTED (start to produce AB), which happens after 10 week incubation period
How is viral load of HIV determined
PCR - detects viral RNA
How is CD4 count determined
FACS - flow cytometry
What is cd4 count used for in HIV Mx
Course of disease
Onset of AIDS (reduction in cd4 T cells)
Define the cd4 count of aids
<200 cells / uL blood
How is resistance to antiretrovirals tested
Phenotypic - viral replication is measured in cell cultures under increased concentrations of the drug then compared to wild type
Genotypic - mutations observed by sequencing of amplified HIV genome
When should treatment be started after diagnosis of HIV
IMMEDIATELY (used to only be if Sx or low cd4)
What is the mainstay of treatment for HIV & what does this consist of
HAART - highly active anti retroviral therapy
2 NRTIs (nucleoside reverse transcriptase inhibitors) and PI (protease inhibitor) (or NNRTI - nonNRTI)
3 benefits of HAART
substantial control of viral replication
Increase in cd4 count
Decline in opportunistic infection and deaths
Give an example of HAART regime
Emtricitabine + tenofovir + efavirenz
(Available as one pill - atripla)
HAART regime in preg for mother & baby (drug, route & when)
Zidovudine
Antenatal PO, delivery IV
PO to baby for 6 weeks to reduce transmission
Limitations of HAART (7)
doesn’t eradicate latent HIV
Doesn’t restore HIV specific T cell response
Toxicities
High pill burden / Adherence
Threat of drug resistance
QoL
Cost
Describe HIV lifecycle
Attachment /entry
Reverse transcription and DNA synthesis
Integration to host DNA
Viral transcription
Viral protein synthesis
Assembly & budding
Which part of HIV lifecycle do attachment / fusion inhibitors target
Attachment and entry
Which part of HIV lifecycle do integrate inhibitors target
Integration to host DNA
Which part of HIV lifecycle do protease inhibitors target
Assembly and budding
Which part of HIV lifecycle do reverse transcriptase inhibitors target
Reverse transcription and DNA synth
Which part of HIV lifecycle do NRTI / NNRTI target
DNA synthesis
Example drug of fusion inhibitors
Enfuvirtide
Side effects of fusion inhibitors
Injection reactions
Drug example of attachment inhibitors
Maraviroc
Examples of NRTIs
Zidovudine
Didanosine
Stavudine
Lamivudine
Zalcitabine
Abacavir
Emtricitabine
Epzicom
Combivir
Trizivir
Side effects of NRTIs
Rare
Fever, GI issues
Specific side effect of zalcitabine / stavudine
Peripheral neuropathy
Which NRTI gives mitochondrial toxicity
Stavudine
Side effect of abacavir
Hypersensitivity
Example of nucleotide RTI
Tenofovir
Side effect of tenofovir
Bone and renal toxicity
Examples of NNRTIs
Nevirapine
Delavirdine
Efavirenz
Side effects of NNRTIs
Hepatitis and rash
CNS effects
Example of integration inhibitors
Raltegravir
Elvitegravir
Examples of protease inhibitors
Indinavir
Nelfinavir
Ritonavir
Amprenavir
Fosamorenavir
Lopinavir
Atazanavir
Saquinavir
Side effects of protease inhibitors
Hyperlipidaemia
Fat redistribution
T2DM
