Session 7: Blood Borne Viruses: HIV Flashcards
4 important viral structures and behaviours to consider concerning viruses.
Genome (RNA or DNA + single stranded or double stranded)
Capsid (Protein shell that protects the genome - is it helical or icosahedral)
Lipid envelope (Present or absent)
Replication strategy
Explain HIV with the viral structure and behaviours in mind.
HIV is a retrovirus meaning it goes from ssRNA -> DNA -> ssRNA
It infects cells with CD4 surface receptors
It replicates inside the cells and destroys them. They cause inflammation and spread to infect more cells.
HIV infects cells with CD4+ surface receptors. Which cells then?
Mainly T helper cells but also monocytes/macrophages.
Explain HIV’s process in a host cell. (Replication)
The free virus binds to a CD4 molecule and one coreceptor. The virus will then fuse with the cell expressing the CD4 molecule.
The virus then penetrates the cell and the contents of the virus is emptied into the cell.
Reverse transcription begins where the ssRNA from the HIV is converted into double stranded DNA by reverse transcriptase enzyme.
The viral DNA is now combined with the host cell’s own DNA by integrase enzyme.
When the infected cell divides the viral DNA will also be read and proteins will be made.
Viralproteins (which are cleaved and become functional) come together and via budding the viral proteins are exocytosed within a vesicle. Non-functional proteins which are not cleaved do not come together.
The new virus although immature breaks free from the infected cell and matures. The viral protein chains will make up ssRNA again. This is why it’s called retrovirus.
Transmission of HIV.
Sexual contact
Transfusion
Contaminated needles (IV drug users mainly)
Perinatal transmission (infected birth canal, transplacental, ingestion of breast milk carrying virus).
Medical procedures such as skin grafts and organ donation as well.
When is HIV most infectious?
After a couple of months of the primary infection. You might not be symptomatic however.
What are the stages of HIV infection.
Primary HIV infection Stage I Stage II Stage III Stage IV or AIDS
Explain primary HIV infection.
Asymptomatic or Seroconversion illness
CD4 count is normal or a temporary drop.
Explain Stage I
Asymptomatic
CD4 count >500
Explain Stage II
Mild symptoms
CD4 count <500
Explain Stage III
Advanced symptoms
CD4 count <350
Explain Stage IV or AIDS.
Severe symptoms or AIDS defining symptoms.
CD4 count <200
Main symptoms/signs of acute HIV infection.
Fever Weight loss Sores in mouth + candidiasis Sores in oesophagus Myalgia Splenomegaly Hepatomegaly Malaise, headache and neuropathy Lymphadenopathy Rash Nausea and vomiting
HIV starts off with the acute symptoms such as lymphadenopathy and thrombocytopenia. As the disease progresses the symptoms will get worse according to CD4 count.
Try to create a timeline of symptoms/signs.
At around 500 you will start getting bacterial skin infections.
400 - Kaposi’s Sarcoma
300 - Hairy leukoplakia and tuberculosis
200 - PCP, Cryptococcis and toxoplasmosis
100 - CMV and Lymphoma
Conditions associated with severe HIV.
Give one for each area affected: Brain Eyes Mouth and throat Blood Lungs Bone Heart Liver Stomach Rep. system Body
Brain:
Meningitis
Toxoplasmosis
Eyes:
CMV
Mouth and throat:
Cold sores and ulcers
Oral candidiasis
Blood:
Hyperglycaemia
Dyslipidaemia
Lungs:
Histoplasmosis
PCP
TB
Bone:
Osteoporosis
Heart:
Heart disease and stroke
Liver:
HCV
Stomach:
MAC
Rep. system: Genital ulcers HPV Cervical cancer PID Menstrual problems Candidiasis
Body:
HIV wasting syndrome
Factors affecting HIV transmission.
Type of exposure like what kind of sexual act.
Transfusion vs. needles tick vs mucous membrane.
Viral load in blood. The transmission is unlikely if undetectable viral load.
Condom use
Breaks in skin or mucous during sexual act (sexual assault can be more likely to cause transmission)
3 most infectious ways of contracting HIV. (Doesn’t have to be the most common ways)
1 - Blood transfusion (90 - 100%)
2 - Receptive anal intercourse (1.11 %)
3 - Sharing needles (0.67%)
Life expectancy in UK in general pop vs HIV.
Gen pop - 80 yrs
HIV - 78 yrs
What makes out a good prognosis of someone who is HIV positive?
Early detection with good CD4.
Regular treatment
Adherence
Healthy living
The later you detect it the worse the prognosis.
Diagnostic tests of HIV.
Blood tests (Serology)
HIV antigen (Ag) - viral protein HIV antibody (Ab) - immunoglobulin
Current tests carried out today detects both Ag and Ab.
However it can give a false negative result. Result on same day.
PCR (polymerase chain reaction. To detect HIV nucleic acid. This is highly sensitive and can detect very early infection. However it is expensive and the result is slow.
There are even more rapid tests to test for HIV that produce a result in less than an hour.
Explain them and why they might be advantageous/disadvantageous.
Usually detect HIV antibody
Can be finger-prick or saliva.
If it is negative it is highly accurate.
However you can get a false positive result. If you get a positive result you need to confirm with serology.
Who should be tested for HIV?
Bacterial pneumonia / TB Meningitis/dementia Sever psoriasis Chronic diarrhoea Unexplain blood abnormality Lymphoma and anal cancer CIN Any STI/Hep B or Hep C
This is in a population where the HIV rate is over 2/1000.
What is used to treat and reduce prevalence of HIV?
Main group
Anti-retroviral drugs (ARVs)
What are the aims of HIV treatment?
To reduce the HIV viral load to an undetectable level.
To increase the CD4 count to a normal level.
Reduce general inflammation to reduce risk of cancer as well
Reduce risk of transmission
Good quality of life
Normalise life span
Referencing back to the HIV replication, where would drugs be suitable to inhibit the replication?
The binding to the CD4 receptors and fusing with the cell. (CCR5 inhibitor)
Inhibiting reverse transcriptase to inhibit the ssRNA to become DNA. (Nucleoside reverse transcriptase inhibitors and non-nucleoside reverse transcriptase inhibitors)
Inhibiting integrase enzyme where the viral DNA is combined with the host cell’s DNA. (Integrase inhibitors)
Inhibiting proteases from cleaving the viral proteins to functional proteins to become a new virus. (Protease inhibitors)
When should you start treatment?
Up until very recently it was when CD4 count got below <350. However now you treat everyone as soon as possible regardless of CD4 count.
What kind of ARVs exist? (Main groups)
Nucleoside reverse transcriptase inhibitors (NRTI)
Non-nucleoside reverse transcriptase inhibitors (NNRTI)
Integrase inhibitors
CCR5 entry inhibitors
Protease inhibitors
Which ARVs would you give in HIV?
In almost all cases give two NRTIs and one additional from another group.
So 3 in total.
Why do you give 3 ARVs?
Because there are millions of rounds of viral replications a day.
The virus also mutates every 2-3 rounds
This means that resistance develops very quickly so if you only have one drug the resistance can develop quickly but with 3 drugs its harder for the virus to develop resistance.
It is important that the patient keeps taking the drugs.
What strategies would you use to treat and reduce the prevalence of HIV?
Increase condom usage Prevention of mother-to-child transmission ARV treatment as prevention Medical circumcision Post-exposure prophylaxis Pre-exposure prophylaxis
Ethical dilemmas in HIV.
Psychological impact of diagnosis Dealing with stigma from lay people Patient confidential vs. Health of mother Health of unborn child Health of sexual contact Health of older child Risk to patients and staff at workplace
