HIV Symposium Flashcards
How many new HIV infections per day?
4000
How many living with HIV in 2021?
~38.4 million
Which age group do 50% of all new infections occur in?
15-24 year olds
What is the UNAIDS 90/90/90 global target? and which country achieved this in 2018?
- 90% people with HIV diagnosed
- 90% diagnosed on ART
- 90% viral suppression for those on ART
UK
What are fast-track cities?
Global partnership between network of HIV burdened cities - affected communities and officals work together to accelerate local HIV responses.
What routes can HIV be transmitted by?
Blood
Sexual
Verticle (parent-child)
What constitutes as high risk behaviours/groups for HIV?
- sexual contact with people from high prevalence groups (eg. MSM, Sub-Saharan Africa)
- multiple sexual partners
- rape
What are the main symptoms of HIV? (6)
- acute generalised rash
- dry cough/SOB/glandular fever
- indicators of immune dysfunction
- unexplained weight loss
- night sweats
- recurrent bacterial infections
What are the prevention methods for HIV?
- male circumcision
- treatment of STIs
- microbicides and condoms
- pre-exposire prohylaxis (PrEP)
Why does male circumcision help prevent HIV?
reduces HIV’s ability to penetrate due to keratinisation
When is HIV not transmittable?
When it is undetectable - if ART and undetectable viral load
What is PrEP?
drugs taken before sex either daily or on demand to prevent HIV transmission
What are the benefits of knowing HIV status?
- access appropriate treatment
- reduction in morbidity and mortality
- reduction in transmission
- beneficial to public health and cost effective
How does early diagnosis of HIV help with costs?
saves on social care, lost working days, benefits claimed, further onward transmission costs
What groups of people should be screened for HIV?
- high risk
- antenatal
- patient-initiated request
- diagnostic
What type of virus is HIV?
Small RNA Lentivirus - member of retrovirus family
What is a lentivirus?
characterised by long incubation period
What is a retrovirus?
uses reverse transcriptase to make DNA copies of itself
Why is HIV hard to recognise?
Not many spike projections and heavily glycosylated so makes it difficult for antibodies to bind
Why does HIV mutate and evolve rapidly?
error-prone replication and large population sizes
What is the mechanism of a virus infecting a cell?
- attachment - of virus to receptors/glycoproteins
- cell entry - ONLY viral core with nucleic acids and some proteins enters host cell
- interaction with host cell - uses host materials to replicate and subvert host cell defence mechanisms
- replication - in nucleus and/or cytoplasm
- assembly - in nucelus/cytoplasm/cell membrane
- release - burst open OR exocytosis over a period of time
How does HIV replicate? (long process)
attachment and entry –> uncoating –> reverse transcriptase RNA to DNA –> genome integration of viral DNA using integrase –> transcription of viral RNA –> mRNA spliced and translated into proteins –> new virions assemble –> budding of immature virus –> maturation protein cut by protease into individual proteins that combine into working virus
What is the main type of T cell that HIV infects?
CD4+
What is gp120?
envelope glycoprotein
What is the result of CD4 and gp120 binding?
produces conformational change in gp120
What makes up the structure of the CD4-gp120 co-binding site?
conserved bridging sheet and amino acids in V3 loop
How does HIV gradually damage immune system?
Depletes CD4 T cells
Why is HIV a lifelong disease?
Once viral integration has occured, infection persists in reservoir of latently infected cells
HIV symptoms at CD4 count of 200-500?
- vaginal/oral candidasis
- skin disease
- fatigue
- bacterial pneumonia
- herpes zoster
- fever/diarrhoea/weight loss
HIV symptoms at CD4 count of 50-200?
- kaposi’s sarcoma, non-hodgkins lymphoma
- pneumocystis carinii pneumonia
- toxoplasmosis, oesophageal candidiasis, cryptococcosis
- CNS lymphoma
HIV symtpoms at <50 CD4 count?
CMV and mycobacterium avium complex
What does Pol gene encode?
reverse transcriptase, protease, integrase
What does Env gene encode?
envelope proteins, eg. gp120
What does Nef gene increase?
infectivity
What does Tat gene contribute to?
viral replication, production of host transcription factors
What does Gag gene encode?
structural proteins, polyproteins
What does Rev gene bind to and allow?
binds to viral RNA and allows exit from nucleus. also regulates splicing
What is the consequence of HIV being able to pass directly from cell-to-cell?
inaccessible to antibodies in blood
When and where is the loss of CD4 cells the biggest in HIV infection?
Early acute HIV in lymphoid tissue in the gut
What is the consequence of loss of CD4 cells in the gut?
Makes gut mucosa leaky, so bacteria can pass through and stimulate immune cells. Leads to chronic immune activation that exhausts immune system
What other factors contribute to immune activation?
directly through inflammatory cell death and co-infections
Why can’t the HIV strains be neutralised quickly enough?
key responses (CD4 T cell) are infected by HIV first
What do CD8 cells use to control viral replication?
HLA class 1 molecules
What is the function HLA class 1 molecules?
present peptides with different characteristics that can come from any part of the pathogen (can include conserved structural and functinal internal proteins).
What does HLA 1 recognition trigger?
release of soluble anti-viral factors and the death of the infected cells
There are critical parts of the viral envelope which are needed to enter CD4 cells. Where are these located?
deep pockets overhung by sugar molecules - only reveald when virus docks onto CD4
What can change without affecting virus function?
the envelope (gp120) proteins
What is the role of cytotoxic T lymphocytes in response to HIV infection?
appear early and exert pressure on the virus so variants emerge which can escape recognition and cause rise in viral road
What is the differene between HLA A/B and C expression?
A/B are down-regulated to undermine CTL killing of infected cells, but C are maintained to prevent NK cell killing
Why is life expectancy still reduced in people with HIV despite medication?
- issues of adherence, side effects, and drug resistance
- increase in non-AIDS defining illness, eg. lung and CVD
- reservoir of latently infected cells persist even with ART
What does life expectancy relate to?
- size of latent HIV reservoir
- persistent immune activation
- co-infection
Who is most at risk of HIV?
MSM, heterozexual women, injecting drug users, commercial sex workers, heterosexual men, truck drivers, migrant workers
What requirements would you have to meet to be cured from HIV?
- absence of viral replication without ART
- viral load remains below detection
- no CD4 decline
- no risk of onward transmission
How does male circumcision reduce HIV transmission?
reduces ability of HIV to penetrate due to keratinisation. foreskin also contains langerhans cells which are prime targets for HIV and can also have abrasion/inflammation which would facillitate passage of HIV
What are the 2025 <10% targets?
- < 10% of people living with HIV and key populations experiencing stigma and discrimination
- < 10% of people living with HIV and women/girls experiencing gender-based inequalities or violence
- < 10% of countries having punitive laws and policies
What are the 2025 > 95% targets?
- 95% of people at risk using combination prevention
- 95/95/95 HIV testing, treatment, and viral suppression
- 95% of women access sexual health services
- 95% coverage of services for eliminating verticle transmission
- 90% of those with HIV receiving TB prevention treatment
- 90% with HIV and those at risk linked to other integrated health services
What global factor has big impact on containment and spread of HIV?
poverty and socio-political factors
Why can HIV affect both high risk groups and general population?
epidemic at different stages in different regions
Why are people with HIV 30-50% more likely to die from covid?
covid vaccine doesn’t reach countries with highest HIV prevalence
WHat percentage of people in sub-Saharan Africa do not know HIV status?
~20%
What are consequences of high HIV prevalence in sub-Saharan Africa?
significant impact on life expectancy and distortion of healthcare spending
What are the 3 routes of transmission in paediatric HIV infection?
- in utero - transplacental
- intra partum - exposure to maternal blood/secretions in delivery
- breast milk - ingestion of contaminated milk
Why is untreated HIV infection particularly aggressive in African infants?
- abundance of HIV target cells
- immaturity of immune system
- genetic similarity to virus donor
- high incidence of co-infections
What kinds of comorbidities can children with delayed diagnosis of perinatal HIV experience?
heart muscle abnormalities, chronic lung disease, growth failure, osteoporosis
Which two markers are used to monitor HIV infection?
- CD4 cell count
- HIV viral load
A patient comes in with fever, rash, and other non-specfic symptoms. What should you ask about?
sexual history and HIV seroconversion
What 3 signs should you test for HIV for?
- unexpected patient with common problem
- no clear underlying cause
- recurrent infections
What type of rash is HIV?
symmetrical maculopapular rash that can involve the whole body
What is a differential diagnosis for HIV rash?
syphilis
When do symptoms usually begin in acute HIV?
2-4 weeks then undergo period of clincal latency which is usually asymptomatic.
What are the main non-specific symptoms of HIV?
- mouth ulcers and sore throat
- fever and headache
- lymphadenopathy
- myalgia
- vomiting/diarrhoea
- weight loss
What infections should prompt a HIV test?
shingles, thrush, oral leucoplakia (caused by EBV), molluscum contagiosum
At what CD4 count are you diagnosed with AIDS?
CD4 <200
What is the most common AIDS defining illness/opportunistic infection?
pneumocystis pneumonia (PCP)
What are the symptoms of PCP?
fever, SOB, dry cough, pleuritic chest pain, drop in o2 sats
What is PCP treated with?
co-trimoxazole (and prednisolone if hypoxic)
What cancers are increased in risk with HIV?
Kaposi’s sarcoma, lymphomas, cervical/penile/anal, hepatocellular carcinoma
What CNS presentations can occur with HIV?
- TB
- CNS lymphoma
- cytomegalobirus retinitis
- ocular toxoplasmosis
- cryptococcal meningitis
What is there a low threshold for in patients with HIV and a headache?
lumbar puncture
What is HAART?
highly active antiretroviral therapy, usually 3+ drugs that act on different points in viral replication cycle
Why is good adherence and avoiding drug interactions key in HIV prognosis?
- suppresses replication
- avoids drug resistance
