HIV virology Flashcards
When was HIV first reported in the UK?
December 1981 - 2 cases
What were the first reported cases of HIV in the UK?
49 year old homosexual male with PCP and CMV infection
29 year old homosexual male with Kaposi’s sarcoma, CMV and cryptococcal pneuomnia
What are the names of the two distinct HIV viruses?
Human immunodeficiency virus 1 and 2
Where did HIV 1 originate from?
Related to viruses called Simian immunodeficiency virus (SIV) found in chimpanzees and gorillas in West Africa
Where did HIV 2 originate from?
Closely related to SIV found in the Sooty Mangabey
When were the HIV viruses thought to cross species?
Crossed from primates to humans in Africa in the late 19th century or early 20th century.
How did the virus jump species?
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
Which factors triggered and epidemic of transmission?
Social changes
Urbanisation
Unsterile injections - vaccines, antibiotics, sleeping sickness
Genital ulcer diseases and sexual promiscuity
What was the first confirmed case of HIV in Africa?
1959 Congolese man
- HIV-1 infection detected in blood sample from a man in Kinshasa
- unknown whether he developed AIDS or not
How did HIV spread from Africa?
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.
Why does HIV spread most quickly though the male gay community?
Combination of sexual promiscuity and high transmission rates associated with anal intercourse
When was the first reported case of AIDS?
1981 - when prevalence of HIV infections in some communities was around 5%
What are the most at risk groups for developing an HIV infection?
Men who have sex with men Black African Women Black African Men Other women Other men IVDU
How is HIV transmitted?
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.
What activities allow HIV transmission?
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
Which cells does HIV affect?
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
How does an HIV infection cause depletion of CD4 T helper cells?
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
When is a person at most at risk when they have an HIV infection?
Once CD4+ cells fall below a critical level (less than 200) the person is a risk of opportunistic infections and some cancers.
What is the genetic contents of a HIV virus?
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
What are the enzymes with the conical capsid containing the viral RNA?
Reverse transcriptase
Proteases
Ribonucleases
Inegrase
Describe the viral envelope for the HIV virus?
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
Describe the HIV protein that is embedded in the viral envelope and protrudes through the surface of the virus?
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
What is the function of the Env protein?
The glycoprotein complex enables the virus to attach to and fuse with target cells
- often targeted in treatment
Where are the possible targets in an HIV lifecycle?
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
What is viral HIV latency?
The long asymptomatic period between intial infection and advanced HIV (AIDS)
HIV still replicates actively in this time
Can HIV be cured?
Once HIV genetic material is incorporated into host DNA, there is no way to remove it
Can HIV be resistant to drugs?
Yes
- a person can be infected with a drug resistant strain
- or the virus can mutate in the body and become resistant
How can a person reduced risk of drug resistance?
Drug-resistant testing - identification of which HIV medications will be effective against the HIV so am appropriate treatment regimen can begin
Medication adherence
What are the clinical markers of HIV
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)
How many CD4+ cells indicates clinical HIV?
HIV negative - 600-1200 per mm3
Therapy starts ideally at counts above 300/mm3
Risk of opportunistic infection increases sharply below 200/mm3
Once infected, how long do you have to prevent clinical HIV?
It takes 3 days for the virus to reach the RES system, and HIV prophylaxis can be used in this time to prevent integration
What is primary infection?
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
How long does clinical latency last and why is it dangerous?
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
What happens once the clinical latency period is over?
Once the clinical latency period is over, there is increased CD4+ cell death which leads to constitutional symptoms (again) and opportunistic diseases
What normally kills a person with advanced HIV?
Opportunistic diseases that infect them due to their inhibited immune system
What constitutes a high viral load.
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)
As CD4+ levels drop, what opportunistic infections may occur?
Thrush Oral hairy leukoplakia TB Histoplasmosis Cryptococcosis Toxoplasmosis Atypical herpes simplex Cytomegalovirus disease
What are the main symptoms of an cute HIV infection?
Fever, weight loss Sores, thrush Pharyngitis Headache, neuropathy and malaise Lymphadenopathy Maculopapular rash Nausea, vomiting Splenomeagly/hepatomeagly Myalgia
What are the possible differential diagnoses for an acute HIV infection?
Secondary syphilis
Mono
Drug rash
Viral infections - CMV, rubella, influenza, parvovirus
Which indicators prompt an HIV test?
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
Currently, when is a person with HIV eligible for anti-reteroviral therapy?
If they have a CD4+ count of 500 or less OR/AND Serodiscordant couples Pregnant women Children under the age of 5
What is HAART?
Highly active anti-reteroviral treatment
- triple therapy
- 2 nucleosdies and 1 drug from another class
- aims to make viral load undetectable
- CD4+ recovery
What are nucleosides in relation to HIV treatment?
Drugs that prevent the action of reverse transcriptase - so RNA can’t be converted to DNA
- NARTIs or NRTIs
What are the challenges with anti-reteroviral therapy?
Good adherence is essential Psychological impact Short-term side effects Drug-drug interactions Emerging longer term toxicities
What are the possible short-term toxicity side effects of ART.
Rash
Hypersensitivty (Abacavir and Nevirapine)
CNA side effects (Efavirenz) - sleep distrubance, vivid dreams and mood changes
GI side effects
Renal Hepatic
Which drugs are known to interact with ART?
PPIs
Statins
Antipsychotics - QTc
What are the possible long term toxicity side effects of ART?
Body shape chnages - lipatrophy or lipodystrophy Renal (Tenofovir) Hepatic Lipid Bone
How is mother to child HIV transmission prevented?
Treat the mother during pregnancy
Treat the baby early on
Universal antenatal HIV screening
Are HIV+ mothers allowed to breastfeed?
Yes - provided the mother and baby are being treated effectively, then there is minimal risk
Given that HIV is treatable long-term, why do people still have so many complications?
Asymptomatic for many years
- most are diagnosed late
- 25% of people with HIV don’t know they have it
When should you offer an HIV test?
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
What is the overall prevalence of HIV in Glasgow in the MSM population between the ages of 16 and 59?
4.5%
What is the prevalence of HIV in Glasgow in the people of African descent population between the ages of 16 and 59?
Overall - 3.2%
Females - 4.6%
Males - 1.9%
Highest in West Dumbartonshire
