HIV - epidemiology and treatments Flashcards
1981 was the first incidences of an increase of men dying from which 2 main things?
pneumonia from the p. jirovecii yeast like fungus
generalised lymphadenopathy - enlargement of lymph nodes
Due to the low CD4 + count
describe the features/quick facts about HIV
retrovirus with a 9kb genome
uses the host rna polymerase to replicate new viral RNA and can even use host cell lipid envelope
has a long incubation period
> it is a lentivirus, a subtype/GENUS of retrovirus that can infect mitotically active+inactive cells (neurons, blood, myocardial cells)
name the three main gene groups that make up a HIV protein. What proteins do they encode?
gag/group specific antigen genes: transmembrane glycoproteins, surface proteins
env/viral envelope genes: capsid, capsid protein, matrix protein, histone like proteins
pol/polymerase genes : reverse transcriptase, proteases, integrases
discuss the gene structure of a HIV virus
encodes 3 genes that each encode different viral long proteins. these viral long proteins then get processed to form a functioning protein
how does HIV infect host cell ~ process
- attachment - viral glycoprotein initially binds to CD4 receptor and secondary binds to the chemokine receptor CCR5 with high affinity
- fusion - viral capsid is internalized and rt and integrase activity creates a ds viral DNA copy that is integrated into host chromosome
- transcription+ translation - Tat and Rev transactivators switched on and viral mRNA is processed and protein processing assembly occurs
- assembly + release - cell membrane buds as the new viral particles leave the cell and host cell is destroyed as a result
> or cell can become latent
what are the indicators/ symptoms of HIV infection
LOW cd4 count
> as cd4 cells underpin the adaptive immune response, through recruitment of other immune cells and stimulators of antibody production, without them individuals are highly susceptible to diseases
recurrent bacterial and yeast infections (TB, candidiasis), pneumonia and more at risk of cancers (lymphoma, kaposis sarcoma)
how would one go about diagnosing HIV? what distinguishes this from AIDs?
AIDs is late stage HIV infection following the latency period
Look at serum levels of CD4+ cells, viral count and antibodies against HIV envelope proteins
> during initial infection, high viral count but this lowers during latency period
> during late stage/AIDS, viral count increases and CD4+ diminishes
why does the CD4+ count change over the course of HIV infection?
initially, as the viral count (viremia) is so high, more CD4+ cells are dying so the cell count decreases
but during the latency period, the viral count decrease and the CD4+ count can recover and even rise before diminishing rapidly during late stage/ AIDS infections
what aspect(s) of HIV makes it hard for the bodies adaptive immune system to effectively combat the disease? /// What makes HIV so difficult to find a cure?
As the virus can hijack the host cells own lipid membranes, the virus is not recognized as foreign by the immune system so the antibodies produced against HIV are not neutralizing
its latency means it can evade the immune system
the mucosal linings are most affected and they lack neutralising antibodies in the first case
HIV also has a high sequence diversity/ high mutation rate so constant drug development is needed
what is a quick diagnostic test for HIV
you can use the ELISA test to detect antibodies against HIV even 4-8 weeks after an initial infection so great for early diagnosis!
there are also rapid tests that can detect the HIV antigen
quick facts about HIV// global aspect of it
4th greatest casue of death, patiucalrly in central africa where 10M affected by HIV2 variant
HIV1 common variant
its a worldwide disease
what dies HIV mean
human immunodeficiency virus
its an aqquired immunodeficiency syndrome
how can HIV be transmitted. Name some risk factors for HIV
bodily fluids - sexual, blood (infections), more at risk if you have multiple sexual partners
medical procedures - infected needles (as seen in hemophiliacs who need to inject VitK clotting factors and generally unsterile equipment
what is a good range of CD4 count to have in cells
healthy indiviuals have above 1000 per ml of blood
lower than 500 per ml is during initial infection
what nature of the viral life cycle makes it hard to cure HIV?
Rt of Viral genome and recombination into host DNA is error prone as it the DNA replication process =
therefore new varients of HIV can form which can be drug resistant
> better to develop multiple drug therapies as seen in PrEP therapy
also using the host lipid membrane means it can evade the immune system
are only T-helper cells affected/destroyed by HIV virus?
All CD4+ positive cells such as T helper cells, macrophages, dendritic cells and astrocytes are susceptible to HIV.
> hence why its called immunodeficiency virus :0
describe the general mechanisms surrounding the HIV drugs developed in the early 80s onwards
the different drugs act to block different aspects of the viral replication cycle
can you name some examples of HIV drugs
rt inhibitors (nucleoside analoges) such as Azidothymidinde 1987 which helped to prevent permanent viral integration
protease inhibitors prevented the protein processing
integrase inhibitors
fusion inhibitors blocking the virus from fusing with the cell membrane
entry inhibitors that block the CCR5 chemokine receptor so prevent internalisation of the virus
> drug development is a continuous process as the virus can become resistant to previous drugs
what is HIV PrEP
it is Pre-exposure Prophylaxis which is a combination of 2 rtInhibitors Emtricitabine and Tenofovir. Aimed to reduce the risk of getting HIV so its a preventative drug
can increase risky behaviors as individuals can think they are protected and its expensive so not accessible to all
what is HIV ART
antiretroviral therapy: uses a cycle of different drugs to keep viral count low and prevent the progression of AIDS so keep within the latency period of below 4530 RNA/mL
As the viral load is low, the transmission rate should also be low too!
» as there are cycles of drugs used, it prevents HIV drug resistance
how can we quantify when someone has a low or high viral count?
we can use MOLECULAR DIAGNOSTIC TESTING to do this
viral load assays (VLA) quantify the number of RNA genomes in the blood
> below 4530 RNA/mL is latent. abov e 36000 RNA/mL is rapid disease progression -> early AIDs onset
discuss the epidemiological origins of HIV virus
Epidemiologic and phylogenetic analyses imply that HIV was introduced into the human population around 1920 to 1940. Likely evolved from the Simian immunodeficiency virus from the great apes
likely this zoonosis occured during the bush meat trade and transmisision through infected blood
> very likely to have been in D.R.Congo Kinshasa 1920 which was a central transportation hub to the bush meat trade and the sex trade
name the different HIV subgroups
On the basis of phylogenetic analysis, HIV1 is divided into subtypes M, N, O
M is the main contributor to the HIV pandemic whilst N and O have remained endemic to African continent
what are bNAbs?
broadly neutralising antibodies
shown in some people with longterm HIV infection who dont go onto to develop aids and shown to improve immunity in these individuals
they are able to keep the viral count low!
so creating a synthetic version of these bNAbs and made them trispecific to target 3 antigens - the envelope, gp120 and gp41 proteins which are found on 99% of all HIV
what is patient compliance and adherence? how has the pandemic affected HIV adhernece?
compliance - do they take the medicine or not
adherence - are they taking the correct amounts/dosages of the medicine
the pandemic has resulted in HIV treatment disruptions, especially for ART treatments.
marginalized and economically disadvantaged groups most affected with people running out of ART tablets at some point within the pandemic.
stockpiling has allowed patient adherence to remain unchanged but this is not sustainable
> also need to take tablets with food so this brings into the issues of food insecurity
what cell type does HIV target?
HIV taegets CD4+ T-cells
this impairs cell-mediated immunity so indiviuals are more at risk at developing cancers and having oppurtunistic infectiosn
how can HIV be transmitted?
sexual intercourse
mother to baby trasmission
in the blood
