HIV Flashcards
Origins of HIV
When was it rife
evolved from SIV, simian immunodeficiency virus, from apes in Africa, jumped to humans around 1920
1980s massive global spread (air traffic accessible to all)
peak epidemic 2004
to date over 40 million deaths
HIV is what type of virus and what is that/ how work briefly
HIV is a retrovirus, has RNA genome
uses reverse transcriptase to convert viral RNA to DNA
viral DNA is integrated into host cell’s DNA, allowing retrovirus to replicate
may endogenous or exogenous
endogenous vs exogenous retrovirus
endogenous:
- stably integrated into human genome, forms normal genetic elements
- transmit vertically like a mendelian gene
exogenous
- transmit horizontally, human to human
structure of HIV
external lipid bilayer and glycoprotein envelope
internal protein core
Gp120
Gp41
what is Gp120 on HIV
Gp120 has docking glycoprotein function
for binding to host cell receptors
what is Gp41 on HIV
Gp41 has transmembrane protein function
mediates fusion process
Gp120 binds to what type of receptors
Gp120 binds to CD4 receptors
mostly on lymphocytes, also on monocytes, macrophages, any cell with CD4 receptors
how does HIV infect target cell? brief
- Gp120 binds to CD4 receptors
- Gp41 virus-cell fusion
- virus loses membrane within cell, viral genome free in cell
- reverse transcriptase into single stranded proviral DNA, then double stranded
- HIV integrase integrates proviral DNA into host DNA, programmes to make copies of virus (replication
- viral assembly, facilitates by HIV protease
- released from cell via budding
how does HIV infect target cell? more detail
Gp120 binds to CD4 receptor on host cell
(ie T helper cell)
Gp41 enables virus-cell fusion
virus loses its membrane once within cell (capsid and matrix digested), genetic material now free in cytoplasm
reverse transcriptase transcribes 1 SS viral RNA to SS proviral DNA, reverse transciptase turns to double stranded proviral DNA
HIV integrase integrates proviral DNA into host DNA
host cell programmed to make copies of viral genome, replication
viral assembly- viral genome packaged into mature virion with a membrane, facilitated by HIV protease
once mature released from cell via budding into blood to infect other
name enzymes involved in HIV infecting target cells, what do they do
reverse transcriptase- transcribes viral RNA into proviral DNA and single to double stranded
HIV integrase- integrates proviral DNA into host DNA
HIV protease- facilitates viral assembly
what happens to the cell once virus has infected, been replicated and left cell
host cell death, usually by apoptosis or CD8+ may recognise virus being expressed alongside MHC class 2 and kill the T helper cell, destroying immune function
what cell population does HIV infection affect most, what do we see in this population after infection
HIV causes progressive decline in CD4+ T helper cells
what is normal range for CD4+ count?
at what point see signs immunosuppression
at what point serious opportunistic infctions
at what point severe immunosuppression
what unit is this
normal range CD4+ count >500-1500
<350 signs of immunosuppression
<200 serious opportunistic infections
<50 severe immunosuppression
cells per mm3
timeline of HIV infection
HIV copies vs CD4+ copies
when first infected (first 12 weeks or so):
CD4 plummets, recovers as body makes more
viral load rises lots and rapidly, highly infectious
clinical latency period:
CD4 count slowly decreases, see progressive decline
viral load stable, slowly rises towards end as CD4 reduces
immunological exhaustion:
CD4+ cells ran into ground, HIV copies rocket
see opportunistic diseases, eventually death
when are the most infectious periods/ when most likely transmitwhen someone has HIV
when first infected when CD4 plummets and HIV rockets. Person has no/ few symptoms so likely time of transmission
immunological exhaustion very infectious but very weak so unlikely to transmit
how long does it take to get from HIV to AIDS if no treatment
could be 3-5 years, could be 20 years
in HIV, what does risk of opportunistic infection depend on
CD4 count
what are the most common opportunistic infections in HIV
herpes salmonella cerebral toxoplasmosis (protozoal infection, presents like a stroke) candidiasis varicella zoster kapose sarcoma
what is the leading cause of HIV+ death worldwide
TB
How is HIV contracted
sexual transmission (unprotected sex)
- facilitates by co-existing STDs
- risk incr by number partners
- most common method transmission
contact with infected blood/ bodily fluids
- dirty needles, bad blood transfusion
mother to baby
- birth and breastmilk
- can give baby short course ART before birth to prevent transmission, use formula
HIV prevelance worldwide
70% of world HIV+ population sub saharan africa
low in EU, USA
do some people have natural immunity to HIV
yes, most prevelant in EU population as mutation arose during black plague
mutation in CCR5 gene, a co-receptor for HIV
if both alleles have mutation, cannot be infected with HIV
if 1 mutated allele have delayed disease progression
HIV UK epidemiology, risk groups
highest risk groups:
MSM
black african
IV drug users
40% are late diagnosed
20 LAs with >5/1000 people HIV=
- highest HIV prevelance London, 18/20
- Manchester
- Brighton
when to offer HIV test
if have risk factors:
- have a blood borne virus eg hep b and c
- has an opportunistic infection
if an emergency admission in a high prevelance area
exposed
what do HIV blood tests look for
HIV antibody presence indicated infection
4th gen tests test for HIV antibody and p24 antigen, shorter window period
3rd gen tests just HIV antibody
why window period HIV
takes time to make antibodies, up to 3 months, so may be too soon to detect
at 4 weeks 95% will have antibodies
at 3 months 99.9% have antibodies
how long after exposure is HIV testing offered
test at 4-6 weeks with 4th gen, repeat at 12 weeks
if test positive for HIV, what else is tested
HIV viral load count
CD4+ count
HIV drug resistance test
is there a chance of transmitted resistance to HIV drugs
yes, 10-20% chance
an opportunistic infection?
only affects those with impaired immune system. Healthy people wouldn’t be affected
pneumocystis pneumonia is?
an opportunistic fungal infection
seen in HIV pts off ARTs, w CD4 under 200/ml
symptoms:
increasing SOB, hypozaemia, fever, dry cough
progresses over time, can die from resp failure
inflamm, damage, failure due to inflamed cells and inflamm debris
give oral steroid course
How do ARTs work
antiretroviral drugs. suppress HIV replication, preventing CD4+ cell death and immunological exhaustion, allows for immune reconstitution
drugs that block every step of retrovirus lifecycle
- fusion/entry inhibitors
- reverse transcriptase inhibitors
- integrase inhibitors
- protease inhibitors
give AT LEAST 3 drugs in combi
why is it important to give at least 3 types of ART in combi
to prevent replication
if only 1/2 types of ART virus mutates and drugs become ineffective, viral resistance
nb mixing other meds with ART
ART can inhibit/ induce an enzyme in liver (cytochrome P450)
this leads to toxic or sub-therapeutic levels of co-administered meds, must always check drug interactions so not to reduce their efficacy
eg statins, oral contraceptives, older anti epileptics
after 6 months ART onwards
irrespective of CD4 count, :
not at risk for HIV assoc opportunistic infections
CANNOT TRANSMIT to sex partner
as long as not diagnosed late have same life expectancy as HIV-
U=U
undetectable= untransmissable
HIV disclosure to partner etc against consent
no legal obligation, but GMC allows and ethically should
if cannot convince HIV+ to disclose and are NOT undetectable on ART, not taking ART, unsafe sex, the partner is at high risk of serious communicable disease. then disclose
procedure for disclosing HIV status to partner without consent
encourage PLHIV, allow time
make them aware of the law on this area
tell them you will inform
what is the law on reckless transmission of HIV
reckless transmission= knowingly infecting another is a criminal offence
in England and Wales, transmission must occur
in Scotland, only risk of transmission needed
could end up being GBH
discrimination and stigma HIV today
2010 equality act protects HIV+
1 in 3 PLHIV fear being rejected by partner
1 in 5 have been
1 in 5 have been excluded from family events
only 45% of public can correctly identify how it is transmitted
for gay men, fear and shame seeps over from past
prevention measures HIV
safe sex- condom and lube
PrEP
PEP
how do LGBT foundation help w condoms
free postal delivery condoms and lube
distributed to barbers, clubs etc in gay village
also do loads to support and inform
PrEP
used by HIV- at risk of HIV+ to prevent getting
86% effective
can be bought online, recently made NHS
dosage depends on method of sex
need full -ve screen first and full STD screenings regularly
PEP
post exposure prophylaxis
must be started within 72 hours
28 day course
available GUM and A+E
what is HIV wasting syndrome
seen in late HIV
over 10% unintentional weight loss
malabsorptionm weakness, deficiencies, diarrhoea, fever
exacerbates illness, incr risk death
