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Unit 9 > Week 2: Introduction to HIV/AIDs > Flashcards

Week 2: Introduction to HIV/AIDs Flashcards

1
Q

What is the supposed origin of HIV1/2?

A

Sporadically spread from non-human primates to primates.
Particularly, gorillas and chimpanzees for HIV1 and the sooty mangabey for HIV2

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2
Q

What are the different lineages of HIV1?

A

Four distinct lineages M-P, each lineage will have following variants and mutants
M has the most distinct variants
Each lineage is more common in certain geographic regions

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3
Q

What are the different lineages of HIV2?

A

Eight different lineageas A-H, each with following variants and mutants
Each lineage is more common in certain geographical regions

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4
Q

How are HIV1 and 2 related?

A

Share a common ancestor - similarities
Also have differences in evolutionary origin resulting in distinct features

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5
Q

What are the main differences between HIV1 and HIV2?

A

HIV1 is more common over 90% of cases, whilst HIV2 is rare and mainly only present in West Africa and India
HIV-2 has a lower transmissibility, less likely to cause AIDs mainly due to lower plasma viral loads so less infection of CD4+ cells
Immune response against HIV2 is stronger - higher levels of IL-2 and humoral responses including neutralisation.

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6
Q

What are the main similarities between HIV1 and 2?

A

Same modes of transmission
Same intracellular replication process
Same clinical features

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7
Q

Where is the majority of the HIV burden felt?

A

Sub-saharan Africa (considered endemic)
White homosexual males
Black heterosexual females and children

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8
Q

Give an overview of the biology of HIV/AIDs?

A

HIV infects mainly CD4+ T cells, resulting in progressive loss of T helper cells and immunodeficiency develops.
Patient develops characteristic cancers and infections
Leads to death over approximately ten years if left untreated.
In some individuals disease may be eliminated but treatment mainly slows the progression of disease

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9
Q

Describe how treatment of HIV has changed over time?

A

1994 - zidovudine prevent mother child transmission
1996 - ART blocks replication of HIV
2004 - global plans to roll out ART and reduce AIDS develops
2009 - HIV vaccine provides partial protection to selected individuals and stem cell transplants cure an infected HIV patient

(low importance)

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10
Q

Describe how the diagnosis of HIV has changed over time?

A

1959 - first document HIV case (not known at time)
1981 - immunodeficiency in homosexual men noted
1983 - HIC linked to AIDs
1984 - HIV antibody assay developed
1995 - HIV latency described

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11
Q

What is the prevalence of HIV like in UK?

A

white gay/bi men
Black african heterosexuals (more women)
1 in 3 living with HIV are aged above 50yrs (longer life expectancy and delay before diagnosis)
Majority are diagnosed between 35 and 49

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12
Q

Describe the structure of a HIV virus

A

Lipid envelope (with gp120) and matrix
Capsid - containing p24
Has two identical copies of SS viral RNA - often dimerised together to increase stability and more effective for RNA replication
Contains reverse transcriptase, integrase and protease enzyme

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13
Q

What receptors are needed for HIV invasion and replication in a host cell?

A

Primarily - CD4+
Co-receptors - CCR5 and CXCR4

Binds to HIV attachment proteins gp120

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14
Q

How do the receptors HIV requires for infection link to the tropism of the virus?

A

CD4+ on T helper cells (effector and memory), macrophages and dendritic cells
CCR5 (most common co-receptor in initial infection 0 - T cells, GALT, Macrophages and DC
CXCR4 - mainly only on T cells (late stage infection)

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15
Q

How does the stage of HIV infection affect the co-receptor used?

A

Initial infections - typically CCR5
Late infections - typically CXCR4

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16
Q

Describe the replication process of HIV within the cell?

A

gp120 on lipid envelope binds to primary receptor CD4 on T helper cells (MC and DCs)
second gp120 binds to co-receptor CCR5 (CXCR4)
Causes fusion with cell membrane, releases content into host cytoplasm, capsid fuses releasing viral RNA and proteins
Protease - hydrolysis protease bond in pre-cursor proteins to create functional proteins
Reverse transcriptase - creates pro-viral DNA from RNA
pro-viral DNA enters the nuclease and is inserted into the host genome by integrase
Host machinery produces new viral RNA and used to make viral proteins
Viral proteins move to cell surface and assemble to form new viral particles, which are released surrounded by part of the host cell membrane.
Cleaves glycoprotein forming a mature virus

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17
Q

How does the immune response against HIV actually aid the progression of the virus?

A

1.HIV pro-viral DNA inserted into host genome. Cytokine receptors activated on host T cell - triggers replication of genome including HIV gene leading to higher levels of HIV in the cell - cell death

  1. HIV infects DC, migrates to lymph node - abundant supply of host cells to infect
  2. Proliferation of activated T cells in the periphery increases the target number of Cells for HIV.
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18
Q

What are the different phases of HIV infection?
When?

A

Eclipse phase: 0-3 weeks
Acute phase: 3 to 9 weeks
Chronic phase: 4 to 6 months onwards

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19
Q

What are the features of the eclipse stage of HIV infection?

A

Infects intial cells - may replicate in local tissue - struggles to avoid eradication and achieve amplification/spread
May trigger an antiviral interferon response
Spreads systemically via lymph nodes.
Establishes reservoirs of infection
Invades GALT

20
Q

What are the features of the acute phase of HIV infection?

A

First detection in blood
Flu like symptoms
Antibodies against HIV produced
May have a CD8+ response against HIV
HIV replicates rapidly and spreads throughout the body
High plasma HIV - detectable on test s- high risk of transmission.

21
Q

What are the features of chronic phase of HIV infection?

A

Viral set point established
Progressive CD4+ loss and increase in HIV numbers
Chronic inflammation
Progression to AIDs

22
Q

Describe the relationship between HIV virus levels and amount of CD4+ over the course of infection.

A

Initial rapid increase in HIV and decrease in CD4+ as HIV invades and replicates, is transported in DC to GALT and lymph nodes
50% reduction in HIV and 50% increase in CD4+, activated CD4+ against HIV proliferate, some CD8+ and other antiviral responses decrease proliferation of HIV, depleted number of CD4+ for HIV to infect
A slow rise in HIV and drop in CD4+ as CD4+ restored more targets for HIV so it is able to replicate, combined with less CD4+ create immunodeficiency so less barrier to replication.

23
Q

What are the main transmission routes of HIV?

A

Unprotectes sexual intercourse - most common
Vertical transmission in utero, delivery or breast milk from mother to child
Injection drug use or blood transfusion

24
Q

What sources have a higher risk of HIV acquisition when exposed to the source?

A

Blood transfusions
Vertical transmission

25
Q

How does HIV affect memory CD4+?

A

Can infect directly
Causes depletion of CD27+ CD4+
CD27 consists of alpha chain of IL-7R. HIV infection interferes with IL7 signalling.
Prevents the progression of effector T cell in T memory cell.

26
Q

What are the main ways to diagnose HIV?

A

Measure viral load and target CD4+ cell levels via full and differential blood cell count

27
Q

What are the different HIV testing options?

A

At-home tests: Measures HIV antibodies in blood takes 20 mins to 24hrs
Rapid point of care - finger prick blood sample to measure antigen and antibodies - 20 minutes
Standard point of cate - peripheral blood sample tested for antibodies takes 5-10 days
Nucleic acid test - Measures HIV RNA provides result in a few days, used for high risk exposure to early symptoms

28
Q

What are the NICE HIV testing guidelines in area of higher prevalence?

A

Test all new GP registrants (not diagnosed)
Test all specialist sexual health clients
Test all hospital admission who are already having a blood test
very high areas - test everyone in ED.

29
Q

How does the CD4+ count link to the stage of HIV infection?

A

Below 500 per mm3 is abnormal
Below 350 per mm3 indicates risk for more serious infectious including TB
Below 200 per mm3 indicates AIDs, serious opportunist infectious including pneumonia and oesophageal cadidasis
Below 100 per mm3 - risk of HIV wasting syndrome cancers, cardiovascular, neurological and GIT affects

30
Q

What are the chronic co-morbidities associated with HIV/AIDS?

A

Invasive cervical cancer
Kaposci sarcoma
Lymphoma
HIV wasting syndrome
PPE (itching skin disease)
Leukoencephalopathy (damage to myelin sheath in white matter of brain)
Cardiovascular, GIT and neurovascular problems (glia cells CD4+) due to accelerated ageing conditions

31
Q

What are some common co-infections in HIV?

A

TB
Eosphageal candidiasis
HSV
Penuomina
Salmonella
Cryptococcosis

32
Q

What are some preventative treatments of HIV?

A

Prophalylaxis condoms
Prophalylaxis ART (PrEP)
Post exposure Prophalylaxis (PEP) - given within 72hours of a high risk exposure, typically tenofovir disoproxyl andr raltegravir
Neutralising antibodies - binds to virus and prevents infecting host cells
Male circumcision - removes foreskin sqaoumous epithelium that is very vulnerable to HIV infection
Vaccines

33
Q

What is the key HIV management goal?

A

Reduce viral load to prevent development of AIDs

34
Q

What are the main goals of a HIV vaccine?

A

Are no current vaccines
Are under current clinical trials
Aims to create CD4+ T helper and NK memory against HIV antigens
Focusing on developing mRNA vaccines to express HIV antigens on host cells, identifying adjuvants that may be needed, also looking at designing a vaccine that results in the production of bnAbs (broadly neutralising antibodies) that would be protective against many HIV strains.

35
Q

What are the different classes of Antiretrovital chemotherapy against HIV?

A

Reverse transcriptase inhibitors (NRTIs or NNTRIs)
Fusion/entry inhibitors
Integrase inhibitors
Protease inhibitors
Capsid inhibitors

36
Q

What is a emtricitabine against HIV?

A

Is an nucleotide reverse transcriptase inhibitors
Are prodrugs, so is in vivo modified to an active form
Is a structural analogue of cytidine
When reverse transcriptase is acting on RNA, NRTI can be inserted into the growing DNA chain, however, structural differences in the NRTI prevent further naturally occurring nucleotides from being inserted into the chain resulting in chain termination and inhibition of further action of reverse transcriptase
This inhibits pro-viral DNA production.

37
Q

What is rilprivirine against HIV?

A

Is a non-nucleoside reverse transcriptase inhibitor
Binds directly to the reverse transcriptase and inhibits production of pro-viral DNA from RNA.

38
Q

What are integrase inhibitors in HIV treatment?

A

Example Raltegravir
Inhibits the insertion of proviral DNA into the host genome

39
Q

What are fusion/entry inhibitors in HIV treatment?

A

Examples: maraviroc and enfuvitide
maraviroc : CCR5 co-receptor antagonist
Prevents interactions with HIV gp120 - prevents from entering the host cell
Enfuvitide: binds to lipid envelop subunit, prevents conformational change required to fuse with host cell membrane.

40
Q

What is atazanabir as a HIV drug?

A

Is a protease inhibitor, binds to protease active site
Inhibits HIV protease from creating functional smaller proteins from larger viral proteins produced from proviral DNA.
results in immature and non-infectious HIV particles

41
Q

What is the use of Lenacapavir as an anti-HIV drug?

A

Is a capsid inhibit: interfers with viral uptake, assembly and release
Binds directly to viral capsid
- inhibits capsid mediated transported of viral pro-DNA to host DNA via the nuclear envelope
- inhibits capsid disassembly in the nucleus - so viral DNA can not be inserted into host genome
- reduces capsid protein sub-unit production inhibiting new viral formation

42
Q

What is the use of tenofovir as an anti-HIV drug?

A

Is a pro-drug
Is activated by bi-phosphorylation
Acts as an anti-viral acyclic nucleoside phosphonate
Typically acts as a reverse transcriptase inhibitor

43
Q

What are the principle sites for HIV reservoirs within the body?

A

Lymph nodes
Spleen
Lymphoid aggregates/ GALT

44
Q

Why are lymph nodes typically good reservoirs for HIV?

A

Infects Tfh cells and Follicular DCs, that are found in lymphoid follicles.
ART can reduce T cell activation and reduce inflammatory mediators - producing immunoprivledged areas
ARV drug penetrance into these sites is heterogenous, in times of low penetrance low level viral replication may still occur

45
Q

How are women affected by HIV?

A

HIV incidence tends to be higher in heterosexual women, as semen tends to have a higher viral load than vaginal fluids (so easier to catch from men)
Women have lower viral set point - but infection progresses at the same rate
Women tend to have more adverse effects from drugs and higher risk of cardiovascular complications from HIV?AIDs

46
Q

How are children affected by HIV?

A

Most infected children are in sub-saharan Africa
Diagnosis in children is delayed as maternal HIV antibodies persist for 18-24months - can induce false positive
WHO recommends rapid and violent ART treatment for all children with low CD4+ counts
As infected for longer course of lifespan greater risk fo cardiovascular, neuro and bone complications

47
Q

Why is there inequalities in medicine availability?

A

Degree of government funding - typically less funding in developing/ low income countries (slow development for malaria and TB)
HIV - lots of profit potential as life-long drugs so great consumer market.
Set to change as climate change alters malaria patterns

Unit 9 (15 decks)

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