HIV (example virus) Flashcards
what family of virus is the HIV virus from and why ?
retrovirus family
because it uses reverse transcriptase (RT) to make a DNA copy that becomes integrated into the DNA of the infected cell
is a RNA virus
HIV is a small retrovirus
which genus of retroviruses does HIV belong to ? and why ?
HIV is a lentivirus
lentiviruses cause chronic diseases and are characterised by long incubation periods (slow viruses)
Replication of HIV mechanism
- attachement
how does the HIV attach to the host cell?
step 1 = attachment
Glycoproteins on the HIV molecule allow it to dock and fuse onto the CD4 and then CCR5 receptors of host cell
Replication of HIV mechanism
- what happens after the HIV attaches to the host cell?
step 2 = entry + uncoating
The viral capsid the enters the cell and enzymes and nucleic acid are released
Replication of HIV mechanism
- reverse transcription
what happens after the virus has entered the cell and released its DNA ?
step 3 = Reverse transcription
Using reverse transcriptase single stranded RNA is converted into double stranded DNA
Replication of HIV mechanism
- what happens after the formation of the double stranded viral DNA inside the host cell
step 4 = Genome integration
Viral DNA then is integrated into the cell’s own DNA (in nucleus) by integrase enzyme
Replication of HIV mechanism
- transcription of viral RNA
what’s involved in this stage
step5 = Transcription of viral RNA
When the infected cell divides the viral DNA is read and long chains of viral proteins are made
the mRNA is splices and translated into proteins
Replication of HIV mechanism
- what happens after the viral DNA has been translated into proteins within the host cell
step 6 = Assembly of new virions
Assembly the viral protein chains are cleaved and reassembled
Replication of HIV mechanism
- what is the final step (after the assembling of new virions)
step 7 = Budding
immature virus pushes out of the cell taking with it some cell membrane
Immature virus breaks free to undergo more maturation
Maturation protein chains in the new viral particle are cut by the protease enzyme into individual proteins that combine to form a working virus
what is the primary receptor for HIV on host cells?
CD4
HIV infects cells that express CD4 a
which glycoprotein on the HIV cell envelope binds to CD4 receptor on host cell, triggering a conformational change ?
gp120
Where/when are the targets during the HIV replication cycle for antiretroviral therapy?
antiretroviral therapy drugs are mostly integrase inhibitors
they prevent step 4 genome integration
ie. prevent virus from integrating into host DNA,
HIV-1 has the ability to rapidly mutate (evolve)
how does it do this?
Has Error-prone replication (the enzyme reverse transcriptase makes at least 1 error in every replication cycle)
Has Rapid viral replication (generation time ~2.5 days)
v Large population sizes (~1010 new virus particles produced each day)
what is AHI ?
Acute HIV-1 infection
early stage HIV characterised by high viral load
what symptoms present during AHI?
“Glandular fever” like illness (non-specific symptoms)
Fever, lymphadenopathy
Sore throat, oral ulcers
Skin rash (upper trunk)
May include neurological features
HIV infects CD4-expressing cells
give examples of these
helper T cells aka. CD4 cells
other T cells
dendritic cells
macrophages
summarise the immune response to HIV
- initial vigorous immune response but no demonstratable protective immunity
- HIV infects CD4+ T helper cells early on, decreasing the immune response and immune exhaustion sets in
- Immunological dysfunction
- but ongoing viral replication, leading to clinical manifestations of immunodeficiency. virus rises when CD4 levels drop
- Takes too long to make antibodies → by the time they are generated, the pathogen has mutated and they are no longer useful
OVEARLL: HIV results in gradual damage to the immune system mainly through depletion of CD4 T-cells
why do we struggle to generate effective antibodies to HIV?
HIV-1 virion only has small number of spikes on its envelope which are heavily glycosylated. Makes it hard for human antibodies to bind to them
The envelope proteins can change
Evolves fast to avoid antibody recognition
what are some problems with ART?
(antiretroviral therapy that HIV-infected people live on)
Issues of adherence, side-effects, drug resistance
can’t afford to miss tablets due to the big latent HIV reservoir
what is AIDS?
acquired immune deficiency syndrome
describes a number of potentially life-threatening infections and illnesses that happen when your immune system has been severely damaged by the HIV virus.
ie. AIDS is a list of conditions caused by HIV
what Two markers are used to monitor HIV infection and make prognosis
CD4 cell count – a CD4 count of under 200 is AIDS
HIV viral load – if you can detect a viral load, how high it is
what CD4 count is considered a late diagnosis ?
CD4 count of under 350,
when there has been multiple missed opportunities to diagnose
HIV Epidemiology - global
where are majority of new HIV infections?
over half of new infections are in sub-Saharan Africa
HIV Epidemiology - global
is the new infection rate of HIV going up or down? why?
new infection rate is going down mainly because
- Better access to healthcare
- More effective treatments that prevent infection
HIV Epidemiology - global
is the life expectancy increasing or decreasing for people with HIV?
People are now living long lives with HIV
HIV Epidemiology - global
how is the majority of new HIV infections spread?
heretosexual transmission
HIV Epidemiology - global
what was the UNAIDS goal (targets for 2020) ?
UNAIDS 90/90/90 goals to eliminate pandemic – global target of:
90% of people living with HIV being diagnosed
90% diagnosed on ART (antiretroviral therapy)
90% viral suppression for those on ART by 2020
HIV Epidemiology - global
what was the fast track cities initiative?
global partnership between a network of over 90 high HIV burden cities,
where political leaders, affected communities, city health officials, clinical and service providers, and other stakeholders
work together to accelerate their local HIV responses
Instead of 90-90-90, want 95-95-95 globally
HIV Epidemiology - UK
has the UK achieved the 90-90-90 target?
UK achieved 90-90-90 target in 2018
New HIV diagnosis in decline
Ageing population with HIV, new territory
what are the 3 transmission routes of HIV?
Blood
Sexual
Vertical → ie. mother to child transmission (not called this because implies blame to mum)
Prevention of HIV via sexual transmission:
list some methods
Voluntary medical male circumcision (HIV like the cells in foreskin)
Treatment of STIs (esp ones that breach epithelium)
condoms
HIV counselling and testing
PEP and PrEP
what is the U=U campaign?
Undetectable = Untransmittable
signifies that those who receive effective antiretroviral therapy and have achieved and maintained an undetectable viral load cannot transmit the virus to a sexual partner.
What it has done/aims to do:
REMOVING the fear of sexual transmission
Dismantling HIV stigma
Encouraging people living with HIV to start and stay on treatment
Encouraging people to get tested
what is PrEP treatment ?
Oral pre exposure prophylaxis
highly effective preventative measure GAME CHANGER
take just before sex or daily
eg. used by people who have a partner with HIV
what is PEP treatment?
Post exposure prophylaxis
28 days Combination Antiretroviral Therapy –must be started within 72 hours
Not as effective as PreP
if viral load is undetectable, what does this show?
undetectable viral load = there is viral suppression
the viral is not transmittable
Benefits of being on treatment for HIV (Prep or pep)
Can have healthy baby without HIV
Can have vaginal delivery
Cant spread to partner
Can live normal life span
benefits of testing
early diagnosis is key –>
get access to appropriate treatment and care
Reduction in morbidity and mortality
Reduction in mother-to-child-transmission (MTCT)
Reduction of sexual transmission
Early diagnosis is cost effective – savings on social care, lost working days, benefits claimed, costs associated with further onward transmission
When and why people get tested - what scenarios ?
Patient presents to a clinician with indicators of immunosuppressive disease/seroconversion
Routine screening in high prevalence places eg. sub saharan africa
Antenatal screening - to eliminate vertical transmission
Screening in high risk groups
Patient initiated requests for testing
issues in the UK - why dont doctors test enough?
Underestimate the risk of HIV in their patients eg. in the elderly, in the married
Fear of offending the patient
They don’t think of HIV
Patient presentations that might involve HIV
examples
Does the patient have an unexplained/severe recurrent medical condition?
acute generalised rash (seen on palms)
glandular fever like symptoms
Unexplained wt loss or diarrhoea, night sweats
how do screening tests for HIV work?
Venous blood sample
Window period = 7 weeks post exposure
P24 antigen, will detect the vast majority of infections at 4 weeks
High specificity and sensitivity
what is the more rapid way of testing HIV?
Point of care tests
Finger prick blood
Get Immediate result
But Lower sensitivity and specificity
Can get False positive and negative results
Longer incubation period
however is a way to outreach in to a community and can lead to earlier diagnosis in a non-healthcare seeking individual
what happens if you get a negative result from a HIV test
repeat the test if within window period (eg. negative at 4 weeks, repeat at 7 weeks)
what happens if you get a positive or unclear result from a HIV test
Phone Sexual Health for advice and we’ll arrange an appointment within 48 hours, Explain test “reactive” and needs further investigation
risk factors for HIV
Sexual contact with people from high prevalence groups – MSM, sub-Saharan African/ Thailand
Multiple sexual partners
Rape in high prevalence localities
HIV Epidemiology - global
who is most at risk of HIV?
Men who have sex with men
Heterosexual women
Injecting drug users
Commercial sex workers
Heterosexual men
Truck drivers
Migrant workers
HIV Epidemiology - global
50% of all new infections occurring world-wide are in which age group ?
15-24 year olds
HIV Epidemiology - global
what region is seeing the most rapid rise in new HIV infections?
Eastern europe and central asia
what are the 3 routes of transmission of HIV to children ?
In utero: transplacental, mostly during the third trimester
intrapartum: exposure to maternal blood and genital secretions during delivery
Breast milk: ingestion of large amounts of contaminated milk
what are the 3 routes of transmission of HIV to children ?
In utero: transplacental, mostly during the third trimester
intrapartum: exposure to maternal blood and genital secretions during delivery
Breast milk: ingestion of large amounts of contaminated milk
In a patient with fever, rash and non-specific symptoms:
-Ask about sexual history
-Think of HIV seroconversion
Think about doing a HIV test when faced with a common problem that is:
in an unexpected patient
Is recussing
Has no clear underlying cause
what is the most common opportunistic infection and AIDS defining illness?
PCP
pneumocystis pneumonia (fungal)
what is meant by Seroconversion?
The transition from infection with HIV to the detectable presence of HIV antibodies in the blood.
what is meant by Seroconversion?
The transition from infection with HIV to the detectable presence of HIV antibodies in the blood.
during HIV latency, patient won’t have symptoms
what signs might they have?
Might have persistent generalised lymphadenopathy (enlarged lymph nodes)
symptoms of PCP
Fevers
SOB
Dry cough
Pleuritic chest pain
Extertial drop in oxygen saturations = key feature
how to diagnose and treat PCP
Diagnose with an induced sputum (send for PCP)
Can treat with co-trimoxazole antibiotic (even though it’s a fungus)
aside from PCP, what are other AIDs defining illnesses?
Oesophageal candida
Kaposi’s Sarcom
Wastings syndrome
TB
TB and HIV
is TB in HIV aids defining ?
yes
All patient with TB require a HIV test
TB in HIV at any CD4 count is aids defining
TB and HIV
is TB in HIV aids defining ?
yes
All patient with TB require a HIV test
TB in HIV at any CD4 count is aids defining
what is the formal criteria of AIDS?
CD4<200
OR
AIDS defining illness
HIV increases the risk of any cancer that is associated with a virus
example: which cancer caused by human herpesvirus 8 is usually associated with HIV?
Kaposi’s sarcoma
single or multiple lesions on the skin
Treated with HAART and chemo/radiotherapy
Usually indicates underlying HIV infection
HAART (highly active antiretroviral therapy ) uses how many antiretroviral drugs at once?
3 or more
Aim to reduce viral load to undetectable levels and increase CD4 count
why is using 3 or more different antiretroviral drugs at once effective?
ie. why use triple therapy?
They act on different points in the replication cycle to suppress viral replication
reduced risk of resistance forming to the drugs - - the chances of all the mutations for three drugs arising in a single virion simultaneously by chance are effectively zero.
- Thus so long as three drugs are in the system, resistance will not occur.
how does HIV resistance to drugs develop?
- non adherence (missing doses, spontaneous mutations can occur)
- drug-drug interactions (other drugs interact with antiretrovirals and decrease their effect eg. steroids or recreational drugs)
