HIV virology Flashcards

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1
Q

When was HIV first reported in the UK?

A

December 1981 - 2 cases

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2
Q

What were the first reported cases of HIV in the UK?

A

49 year old homosexual male with PCP and CMV infection

29 year old homosexual male with Kaposi’s sarcoma, CMV and cryptococcal pneuomnia

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3
Q

What are the names of the two distinct HIV viruses?

A

Human immunodeficiency virus 1 and 2

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4
Q

Where did HIV 1 originate from?

A

Related to viruses called Simian immunodeficiency virus (SIV) found in chimpanzees and gorillas in West Africa

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5
Q

Where did HIV 2 originate from?

A

Closely related to SIV found in the Sooty Mangabey

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6
Q

When were the HIV viruses thought to cross species?

A

Crossed from primates to humans in Africa in the late 19th century or early 20th century.

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7
Q

How did the virus jump species?

A

Bush meat theory - a hunter was bitten or cut while butchering an animal
- it isn’t known how SIV transformed into HIV and became capable of replicating in humans

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8
Q

Which factors triggered and epidemic of transmission?

A

Social changes
Urbanisation
Unsterile injections - vaccines, antibiotics, sleeping sickness
Genital ulcer diseases and sexual promiscuity

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9
Q

What was the first confirmed case of HIV in Africa?

A

1959 Congolese man

  • HIV-1 infection detected in blood sample from a man in Kinshasa
  • unknown whether he developed AIDS or not
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10
Q

How did HIV spread from Africa?

A
Spread to Haiti by an unknown person who contracted it in the Democratic Republic of the Congo
A miniepidemic (1969) followed and HIV came from Haiti to the USA
- that single person caused most AIDS cases outside of Sub-Saharan Africa.
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11
Q

Why does HIV spread most quickly though the male gay community?

A

Combination of sexual promiscuity and high transmission rates associated with anal intercourse

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12
Q

When was the first reported case of AIDS?

A

1981 - when prevalence of HIV infections in some communities was around 5%

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13
Q

What are the most at risk groups for developing an HIV infection?

A
Men who have sex with men
Black African Women
Black African Men
Other women
Other men
IVDU
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14
Q

How is HIV transmitted?

A

HIV enters the body through open cuts, sores or breaks in the skin, through mucous membranes such as those inside the anus or vagina, or through direct injection.

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15
Q

What activities allow HIV transmission?

A
Anal or vaginal intercourse (not oral)
Injecting drugs and sharing equipment 
Mother to child
Transmission in health care settings
Via donated blood or blood clotting factors
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16
Q

Which cells does HIV affect?

A

HIV cells infect cells in the immune system such as T-helper cells, macrophages and dendritic cells - as all of these cells carry CD4 receptors which allow HIV entry

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17
Q

How does an HIV infection cause depletion of CD4 T helper cells?

A

Direct viral killing of cell
Apoptosis of uninfected bystander cells
CD8+ cytotoxic T cell killing of infected CD4+ cells
Abnormal B cell activation resulting in excess/inappropriate immunoglobulin production

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18
Q

When is a person at most at risk when they have an HIV infection?

A

Once CD4+ cells fall below a critical level (less than 200) the person is a risk of opportunistic infections and some cancers.

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19
Q

What is the genetic contents of a HIV virus?

A

Two copies of single stranded RNA enclosed by a conical capsid composed of 2000 copies of the viral protein p24
The RNA is tighly bound to nucleocapsid proteins and the enzymes needed for the development of the virion.
A matrix composed of the viralprotein p17 surrouds the capsid ensuring integrity

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20
Q

What are the enzymes with the conical capsid containing the viral RNA?

A

Reverse transcriptase
Proteases
Ribonucleases
Inegrase

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21
Q

Describe the viral envelope for the HIV virus?

A

Two layers of phospholipids taken from the membrane of the human cell when a newly formed virus buds from the cell.
Embedded in the envelope are proteins from the host cell and about 70 copies of a complex HIV protein that protrudes through the surface of the virus

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22
Q

Describe the HIV protein that is embedded in the viral envelope and protrudes through the surface of the virus?

A

Env

  • this consists of a cap made of three molecules (glycoprotein 120)
  • a stem consisting of three gp41 molecules that anchor the structure into the viral envelope
23
Q

What is the function of the Env protein?

A

The glycoprotein complex enables the virus to attach to and fuse with target cells
- often targeted in treatment

24
Q

Where are the possible targets in an HIV lifecycle?

A

Fusion - when the virus fuses to the cell and dumps its contents
Conversion of viral RNA to DNA - so the virus can insert its genetic code into the host cell
Integration - where the viral DNA is inserted into the host DNA
Budding - when the vius buds off from the host cell and goes to infect another

25
Q

What is viral HIV latency?

A

The long asymptomatic period between intial infection and advanced HIV (AIDS)
HIV still replicates actively in this time

26
Q

Can HIV be cured?

A

Once HIV genetic material is incorporated into host DNA, there is no way to remove it

27
Q

Can HIV be resistant to drugs?

A

Yes

  • a person can be infected with a drug resistant strain
  • or the virus can mutate in the body and become resistant
28
Q

How can a person reduced risk of drug resistance?

A

Drug-resistant testing - identification of which HIV medications will be effective against the HIV so am appropriate treatment regimen can begin
Medication adherence

29
Q

What are the clinical markers of HIV

A

CD4+ cell count - assess risk of mortality and morbidity

HIV-1 plasma RNA (viral load test) - how much HIV is present in the blood (infection risk)

30
Q

How many CD4+ cells indicates clinical HIV?

A

HIV negative - 600-1200 per mm3
Therapy starts ideally at counts above 300/mm3
Risk of opportunistic infection increases sharply below 200/mm3

31
Q

Once infected, how long do you have to prevent clinical HIV?

A

It takes 3 days for the virus to reach the RES system, and HIV prophylaxis can be used in this time to prevent integration

32
Q

What is primary infection?

A

Acute HIV syndrome caused by wide dissemination of the virus

  • causes flu like symptoms (sweats, rash, weight loss and fever)
  • occurs within 3/6 weeks of infection
33
Q

How long does clinical latency last and why is it dangerous?

A

It lasts for 2-10 years
The patient normally has a normal CD4+ cell count during this time, and they have no symptoms
- so they don’t know they are infected

34
Q

What happens once the clinical latency period is over?

A

Once the clinical latency period is over, there is increased CD4+ cell death which leads to constitutional symptoms (again) and opportunistic diseases

35
Q

What normally kills a person with advanced HIV?

A

Opportunistic diseases that infect them due to their inhibited immune system

36
Q

What constitutes a high viral load.

A

Below 10,000 is low and above 100,000 is high
Generally - the lower the better
Some people can control the virus better and have undetectable levels (below 40 copies/ml)

37
Q

As CD4+ levels drop, what opportunistic infections may occur?

A
Thrush
Oral hairy leukoplakia
TB
Histoplasmosis
Cryptococcosis
Toxoplasmosis 
Atypical herpes simplex 
Cytomegalovirus disease
38
Q

What are the main symptoms of an cute HIV infection?

A
Fever, weight loss
Sores, thrush
Pharyngitis 
Headache, neuropathy and malaise
Lymphadenopathy 
Maculopapular rash
Nausea, vomiting 
Splenomeagly/hepatomeagly 
Myalgia
39
Q

What are the possible differential diagnoses for an acute HIV infection?

A

Secondary syphilis
Mono
Drug rash
Viral infections - CMV, rubella, influenza, parvovirus

40
Q

Which indicators prompt an HIV test?

A

When any of the acute symptoms are present, even if you are sure it’s not HIV

  • normalise testing and reduce stigma
  • make it a routine medical investigation
41
Q

Currently, when is a person with HIV eligible for anti-reteroviral therapy?

A
If they have a CD4+ count of 500 or less
OR/AND
Serodiscordant couples
Pregnant women
Children under the age of 5
42
Q

What is HAART?

A

Highly active anti-reteroviral treatment

  • triple therapy
  • 2 nucleosdies and 1 drug from another class
  • aims to make viral load undetectable
  • CD4+ recovery
43
Q

What are nucleosides in relation to HIV treatment?

A

Drugs that prevent the action of reverse transcriptase - so RNA can’t be converted to DNA
- NARTIs or NRTIs

44
Q

What are the challenges with anti-reteroviral therapy?

A
Good adherence is essential
Psychological impact
Short-term side effects
Drug-drug interactions
Emerging longer term toxicities
45
Q

What are the possible short-term toxicity side effects of ART.

A

Rash
Hypersensitivty (Abacavir and Nevirapine)
CNA side effects (Efavirenz) - sleep distrubance, vivid dreams and mood changes
GI side effects
Renal Hepatic

46
Q

Which drugs are known to interact with ART?

A

PPIs
Statins
Antipsychotics - QTc

47
Q

What are the possible long term toxicity side effects of ART?

A
Body shape chnages - lipatrophy or lipodystrophy 
Renal (Tenofovir)
Hepatic
Lipid
Bone
48
Q

How is mother to child HIV transmission prevented?

A

Treat the mother during pregnancy
Treat the baby early on
Universal antenatal HIV screening

49
Q

Are HIV+ mothers allowed to breastfeed?

A

Yes - provided the mother and baby are being treated effectively, then there is minimal risk

50
Q

Given that HIV is treatable long-term, why do people still have so many complications?

A

Asymptomatic for many years

  • most are diagnosed late
  • 25% of people with HIV don’t know they have it
51
Q

When should you offer an HIV test?

A

Any possible symptoms present
Patient is part of a high risk group
- but even if they’re not, don’t let that put you off a test

52
Q

What is the overall prevalence of HIV in Glasgow in the MSM population between the ages of 16 and 59?

A

4.5%

53
Q

What is the prevalence of HIV in Glasgow in the people of African descent population between the ages of 16 and 59?

A

Overall - 3.2%
Females - 4.6%
Males - 1.9%
Highest in West Dumbartonshire