Intro to HIV Flashcards
outline the NICE HIV testing guidance
- in areas of high prevalence, offer and recommend HIV testing on admission to hospital to everyone who hasn’t been previously diagnosed with HIV and who is undergoing blood tests for another reason
- in general practice offer and recommend HIV testing to everyone wo has not previously been diagnosed with HIV and who: registers with the practice or is undergoing blood tests for another reason and has not had a HIV test in the previous year
what are the recommendations for the public
- everyone should know their hIV status
- all men who have ever had sex with another man should have a HIV test
- Gay, bisexual and other MSM should have a HIV test at least annually, or 3 monthly if having UPSI with new or casual partners
- people born in countries where HIV is common, should have an HIV test and repeat annually if UPSI with new or casual partners
- anyone who is diagnosed with HIV should accept the clinical recommendation that they start treatment immediately
Give examples of places where prevalence >1%
africa, south America, Asia
what does stigma lead to
discourages people from testing and accessing care
what are the different types of antiretroviral drugs
- fixed dose combinations
- nucleoside or nucleotide reverse transcriptase inhibitors
- non nucleotide reverse transcriptase inhibitors
- integrase inhibitors
- CCR5 inhibitors- entry inhibitor
- b/PI- boosted protease inhibitor
- pharmacokinetic boosters
give examples of fixed dose combination antiretroviral drugs
- atripla
- biktarvy
- eviplera
- odefsey
- trimmeq
- genvoya
- stribild
- symtuza
- delstrigo
- Novato
- juluca
give examples of NRTI antiretrovirals
- tenofovir DF + emtricitabine (truvada)
- TAF + emtricitabine (descovy)
- abacavir + lamivudine (kivexa)
give examples of NNRTI antiretrovirals
- efavirenz
- nevirapine
- etravirine
- rilpirivine
- doravirine
give examples of INI retrovirals
- raltegravir
- dolutegravir
give examples of CCR5 inhibitors
- maraviroc
give examples of b/PI boosted protease inhibitors
- atazanavir
- darunavir
- darunavir/cobicistat
give examples of pharmacokinetic booster antiretrovirals
- cobicistat
- ritonavir
what are the main points of action of ART classes
- entry inhibitors- fusion inhibitors and CCR5 inhibitors
- Reverse transcriptase inhibitors- nucleoside analogues and non nucleoside analogues
- protease inhibitors
- integrase inhibitors
describe the function of CCR5
- co receptor
- for HIV to infect host CD4 cell, has to attach to CCR5, then bind CD4 receptor and fuse to the cell membrane and inject 2 RNA copies into host cell
what is the function of HIV reverse transcriptase
facilitates copying 2 viral sRNA strands into dsDNA
what is the function of integrase inhibitors
integrate viral dsDNA into host DNA
what is the function of protease inhibitors
viral protease chop up long proteins, making newly assembled viral particle ready for action
what other research can be used apart from ARV to control HIV
- vaccines
- microbicides
- eradicating latency in dormant cells
- HIV immunotherapy- cell miutations leading to HIV resistance/eradication
- gene therapy
give examples of combination prevention of HIV
- use condoms wherever possible
- post exposure prophylaxis- prevents acquisition following potential exposure
- treatment as prevention- prevents transmission
- immediate ART now standard HIV care - pre exposure prophylaxis- prevents acquisition before exposure
- expand HIV testing
give examples of intervention HIV prevention strategies
behavioural strategies:
- education and public health campaigns
- condom skills education
- motivational interviewing
circumcision- reduces male to female sexual transmission
what is HIV
human immunodeficiency virus
- attacks immune system, specifically CD4 T cells
- virus replicates inside these cells
- overtime it kills CD4 cells, leading to weaker immune system and reduces ability to recognise infection
- if uncontrolled HIV, body can’t fight serious opportunistic infections (TB, pneumonia) which can be fatal
- no cure, but ARVs stops virus from replicating and damaging immune system
what is the aim of effective treatment of HIV
suppresses virus to low levels so can’t harm patient and can’t pass it on
- low viral load leads to better natural defences and body better equipped to fight infection
when is ART started
immediately after positive HIV test
- increases lifespan
- reduces risk of transmission to others
what is AIDS
- set of symptoms and illnesses due to immune damage by HIV
- also called late stage HIV
how can HIV be passed on
- can’t be passed on by touching, kissing, sharing cutlery
- transmitted by unprotected sex if patient is not on effective ART (most common)
- second most common by sharing needles
- low chance of getting HIV from oral sex but advised to use condoms/dental days to prevent STIs
- higher risk if you have open sores, bleeding gums - HIV absent in sweat- not passed by skin to skin contact
- passed through blood, breastmilk, seminal, pre seminal and anal fluids
- insect bites can’t transmit HIV
- if ARTs started during pregnancy, baby risk of contracting HIV is less than 1%, but without treatment risk is 25%
what is a dental dam
thin sheet of plastic, provides protection during oral sex
give examples of ways to prevent HIV
- getting regularly tested if sexually active
- taking PrEP or PEP
- Using condoms
- never sharing needles
- taking medication as prescribed if living with HIV
who is PrEP given to
people who are HIV negative to reduce the chance of getting HIV
- used where not able to practice safer sex
what is PrEP and how is it taken
- short course ART
- stops exposure to HIV becoming lifelong infection
- prevents acquisition before exposure where potentially at risk of acquiring hiv
- isn’t always available and shouldn’t be used as regular form of protection
why is it important for patients to adhere to HIV treatment
- patients should take at same time every day
- adherence reduces levels of HIV and reduces resistance to antiretrovirals
- regularly missed doses means HIV acquires resistance to ART
when is hIV considered undetectable
- when treatment effectively reduces viral load so low that it can’t be detected in tests
- <40 copies/ml= undetectable - as long as HIV is undetectable, can’t be transmitted to others
- key to have viral load monitored
why is it important to diagnose early
want to diagnose when CD4 count is higher, to reduce risk of death or AIDs diagnoses in first year after diagnosis
describe the Properties of HIV
- retrovirus- back to front
- stores genetic info using RNA instead of DNA
- need to make DNA when enters host to replicate - causes disease slowly
- can’t replicate on its own- infects CD4 cells of immune system and uses host machinery in these cells to replicate
- overtime HIV kills CD4 cells, reducing ability to recognise and fight infection
- if not controlled by treatment, loss of cd4 cells leads to opportunistic infections
- experiencing a collection of these infections is most advanced stage of HIV (AIDS)
describe the structure of HIV
- spherical virus
- outer shell- envelope covered in spikes of glycoproteins gp120 and gp41
- glycoproteins allow HIV to interact with CD4 receptor on T cells - inside virus= matrix
- core of virus is nucleus enclosed in capsid containing reverse transcriptase and integrase
- contains 2 strands of RNA- holds genetic material of hIV
- HIV RNA composed of 9 genes- contains instructions to make new viruses
outline the first step in the HIV lifecycle
attachment and entry (binding):
1. process of HIV gaining entry into a cell through 2 steps: attachment, then fusion
2. hiv infects immune cells with a surface CD4 receptor
3. gp120 spikes on surface of HIV cell locks onto cd4 receptor and another co receptor (CCR5)
4. gp41 protein fuses HIV envelope with host cell wall
5. fusion allows HIV capsid to enter host cd4 cell
give examples of cd4 receptor cells
T lymphocytes, monocytes, macrophages, dendritic cells
what are cd4 receptors used for
used to signal to other immune components and highlight presence of antigens
give examples of ARDs that may block stages of attachment and entry
- CCR5 inhibitors
- attachment inhibitors
- fusi9on inhibitors
what can be used as a target for vaccines in hiv
gp41 and gp120 proteins on surface of virus
outline the second step of the HIV lifecycle
reverse transcription:
1. hiv RNA must be reverse transcribed in the host cell into proviral DNA
2. once proviral dna is created, it is integrated into DNA of host
3. hiv uses viral reverse transcriptase to connect RNA to proviral dna
what types of ARD stop the action of viral reverse transcriptase enzymes
- NRTIs
- NtRTIs
- block HIV replication by inserting a nucleoside/nucleotide into chain of hiv dna which terminates chain
- NNRTIs- block HIV production by directly binding to reverse transcriptase enzyme
what is the 3rd step of the HIV lifecycle
Integration:
1. after HIV RNA is converted to DNA, hiv integrase enzymes attach to end of proviral dna strand and enters host cell nucleus
2. proviral dna then binds to host dna and integrates into host dna
3. hiv integrase inhibitor drugs block transfer of hiv RNA into host dna
4. after proviral dna integrated into host dna, hiv remains dormant in cell
- cell is latently infected
- difficult to detect latently infected cells, even with high sensitivity tests
what is the 4th step of the HIV lifecycle
transcription and translation:
1. cell produces hiv RNA if it recieves a signal to become active
2. cd4 cells activated when encounter an infective agent (antigen)
3. when cd4 cell is activated, hiv uses host RNA polymerase enzymes to make mRNA
4. mRNA provides instructions to make long viral polyproteins (inactive)
5. long chains of hiv proteins cut into smaller chains by hiv proteases which activates them
what is the final step of the HIV lifecycle
assembly and budding:
1. protein chains assemble into new viruses at host cell wall
2. hiv protease inhibitors block activity of hiv protease enzymes
3. as virus buds from cell wall, genome is enclosed in a capsid (produced by hiv gag protein)
4. after new virus is assembled, this leaves out by pushing through cell wall
5. to leave host cell completely and become infectious, virus must take lipids from cell wall and make surface glycoproteins
6. maturation inhibitor drugs being developed to block cutting of gag protein needed to produce mature virus
what is the first clinical stage of infection
- primary (acute) HIV infection- hiv enters body by infecting cd4 cells of mucous membrane of vagina or rectum, or by direct infection of cd4 T cells in bloodstream
- at this stage, PrEP can prevent hiv infection if taken consistently
when can post exposure prophylaxis be used
used with a 3 drug ARD combination
- can prevent hiv up to 72 hours post exposure
describe the role of dendritic cells in hiv
- first cells to encounter hiv
- transport infectious agents to lymph nodes
- when hiv arrives in lymph nodes (24-48 hours post exposure), it activates other immune cells like cd4 T cells
- hiv replicates in lymph nodes
how is hiv detected in lymph nodes
- not detectable in blood by viral blood testing or antibody testing
- only detectable by taking a biopsy of lymph node tissue
- 3 drug ARD initiated in this stage of hiv infection to restrict spread of hiv to cells of immune system which can form a reservoir of hiv
when is hiv not detectable in blood
7-21 days
- several weeks after infection, hiv is detectable in blood by viral load testing
- this is when people may experience symptoms such as fever, body rash, swollen glands
what is the most common symptom of acute hiv infection
fever and rash
- may last up to 2 weeks
- viral load reaches its peak at this time and cd4 cell levels fall
when is hiv antigen (p24) detectable
around 3-4 weeks after infection
- using 4th generation antibody/antigen tests which combine detection of hiv antibodies and hiv antigens and show a positive result
- further 4-8 days- hiv antibody only tests using blood show a positive result
- hiv levels begin to fall and cd4 levels begin to rise
what occurs after 6 months
viral load and cd4 levels stabilise at a level known as set point
what occurs in chronic HIV infection
- hiv gradually reduces number of cd4 cells until cd4 count falls below 200 cells/mm3
- below this, risk of developing AIDS related infections increases
what is the asymptomatic phase
period where hiv doesn’t cause illness
- lasts 10 years on average
- length depends on how quickly cd4 cell count declines
- if very high viral load (>100,000 copies/ml), cd4 cells are lost quicker
what is the role of ART
- suppresses hiv to undetectable levels, restores cd4 count to normal levels and prevents disease if started at any time during asymptomatic phase
- taken daily
- guidelines recommend start taking treatment soon after diagnosis
what monitors progression of hiv disease during asymptomatic phase
cd4 cell counts and viral load tests
where are reservoirs of latently infected cells established
in lymph nodes, spleen and gut
- latently infected cells can proliferate without activation but are not recognised as pathogenic
what is iBASE
community led charity, supporting people living with hiv by providing treatment information
- work closely with hiv specialists
what are needle exchange schemes used for
reduces blood borne virus transmission
- doesn’t encourage drug use but safer drug use for people who are going to use drugs anyway
- hiv more easily transmitted in presence of other STIs
describe the use of treatment as prevention
- prevents transmission u=u
- undetectable= untransmissable - immediate ART now standard hIV care
- if someone is hiv positive and has partner who is hiv negative
describe the use of post exposure prophylaxis
- used for sexual and occupational exposure (needlestick injury)
- within 72 hours of exposure but ideally sooner
- one month course of 3 ARTs- high success rate of preventing conversion
- prevents acquisition following potential exposure
what are the benefits of hiv testing
- improves quality of life of people with hiv by enabling early treatment
- reduces transmission
- can have asymptomatic hiv- testing is only way to know status
- knowing status allows people to get treatment and not pass virus on
- people aged over 16 can order a free hiv test
what is the test and treat programme
- aim for 90% of new diagnoses to be taking ARVsby 30 days
-aim for 98-100% PLWH to be taking effective treatment - aim for 100% PLWH have undetectable viral loads
describe how HIV testing can be expanded to get towards zero undiagnosed HIV infection
- annual testing and increase awareness of testing
- increase availability of tests for targeted populations
- self tests
- pharmacies, primary care - sign post using social media
- use anti stigma campaign/PrEP to further boost testing
