HIV Flashcards
Types of HIV
HIV1 (M responsible for epidemic)
HIV2
Geographical variation - recombinant
Surface antigens and receptors that bind HIV to host cell
GP120 and GP41
CC45 and CD4
How does HIV infect and then dissemninate virus?
Infection of mucosal CD4+ cell (Langerhans and Dendritic cells)
Transport to regional lymph nodes and into gut lymphoid tissue
Infection established within 3 days of entry
Dissemination of virus
Why is neuro disease common in HIV?
Microglial cells have CDD4+ on surface which is target site for the virus
How does HIV infection affect immune response?
Reduced circulating CD4+ cells
Reduced proliferation of CD4+ cells
Reduction CD8+ (cytotoxic) T cell activation
- Dysregulated expression of cytokines
Reduction in antibody class switching
- Reduced affinity of antibodies produced
Chronic Immune Activation (microbial translocation)
Susceptible to: viral, fungal, parasitic, mycobacterial, infection rel cancer
WHich immune response do HIV+ pts retain?
Antibacterial response
(unless severely immunocompromised)
When are people at highest risk of opportunistic infections?
CD4+ Th cells <200 cells/mm3
How long do HIV+ people live without tretament?
Avg 9-11 years post-diagnosis
Most common pres of HIV
Onset average 2-4 weeks after infection (up to 3 months)]
Looks like non-specific viral infection
Combination of:
Fever
Rash (maculopapular)
Myalgia
Pharyngitis
Headache/aseptic meningitis
High risk of this transmission at this point
Features of asymptomatic HIV
Ongoing viral replication
Ongoing CD4 count depletion
Ongoing immune activation
Risk of onward transmission
Define opportunistic infection
infection caused by a pathogen that does not normally produce disease in a healthy individual
e.g. mycobacterium TB, CMVr, cerebral toxo, pneumocystic jiv
Clinical presentation of PCP
Symptoms:
Insidious onset
SOB
Dry cough
Signs:
exercise oxygen desaturation
might be normal chest/ diffuse crackles
Features of PCP on CXR
CXR:
May be normal
Interstitial infiltrates
Reticulonodular markings
Looks a bit like HF except HF normal size
Diag and management of PCP
Diagnosis: BAL and immunofluorescence +/- PCR
Treatment: high dose co-trimoxazole (+/- steroid)
Prophylaxis: low dose co-trimoxazole
WHat TB infections are HIV pts mor likely to get?
Reactivation of latent
Symptomatic primary infection
Drug resistance
Extra-pulmonary
etc etc
Clinical pres of cerebral toxo
CD4 threshold: <150
Reactivation of latent infection
→ multiple cerebral abscess
→ (Chorioretinitis)
Presentation:
Headache
Fever
Focal neurology
Seizures
Reduced consciousness
Raised ICP
Ring enhancing lesions in a pt with HIV?
Cerebral toxo
Clinical pres of CMV in HIV
CD4 threshold: <50
Reactivation of latent infection
→ retinitis, colitis, oesophagitis
Presentation:
Reduced visual acuity
Floaters
Abdo pain, diarrhoea, PR bleeding
Screened ophtho with CD4+ <50
Clinical pres of HIV assoc neurocog impairment (AIDS rel dementia)
CD4 threshold: ↑ incidence with ↓CD4 (incr with longer disease presence)
Presentation:
Reduced short term memory
+/- motor dysfunction
Brain atrophy on MRI
Clin pres of PML
Caused by JC virus
CD4 threshold: <100
Presentation:
Rapidly progressing
Focal neurology
Confusion
Personality/behaviour change
3 main skin infections assoc with HIV
Extensive, treatment resistent, hypertrophic, dysplastic versions of each virus:
Herpes zoster
HSV
HPV (also assoc cervical cancer)
Clinical pres of HIV wasting/Slim’s disease
Severe cachexia
Metabolic (chronic immune activation)
Anorexia (multifactorial)
Malabsorption/diarrhoea
Hypogonadism
Clinical pres of Kaposi’s sarcoma
Caused by HSV
Pathology: vascular tumour in viscera/skin
CD4 threshold: Any. ↑ incidence with ↑ immunosuppression
Presentation:
Cutaneous
Mucosal
Visceral – pulmonary, GI
Management of Kaposi’s
Anti-retrovirals
Local therapies
Systemic chemotherapy if visceral
Clinical pres of non-Hodgkins in HIV
CD4 threshold: ↑ incidence with ↑ immunosuppression
Presentation:
More advanced B symptoms
Bone marrow involvement
Extranodal disease
↑ CNS involvement
Non-AIDS symptoms of HIV
Mucosal candidiasis
Seborrhoeic dermatitis
Diarrhoea
Fatigue
Worsening psoriasis (CD8 rel)
Improvement of RA (CD4 rel)
Lymphadenopathy
Parotitis
Epidemiologically linked conditions (STIs and heps)
Also neuro manifesttations e.g. polyneuropathy
Haem manifestations in HIV
Leuko/lymphopenias (due to ↓ CD4)
Thrombocytopenia (HIV infects megakaryocytes)
Factors incr transmission risk in sex
Anoreceptive sex
Trauma
Genital ulceration
Concurrent STI e.g. rectal chlamydia
Types of parenteral transmission
Injection drug use (not v common anymore)
Infected blood products
Iatrogenic
Features of vertical MtC transmission
May be:
In utero/trans-placental
Delivery
Breast-feeding
If no management:
1 in 4 babies infected
more likely if mother seroconverts while pregnant
Who should be tested for HIV?
Universal testing in high prevalence areas
Opt-out testing in certain clinical settings
Screening of high risk groups
Testing in the presence of “clinical indicators”
Where is HIV testing opt out?
TOP
Sexual health
Addiction/subs misuse
Antenatal
Assisted conception
High risk groups in HIV
MSM
Female partners of MSM
People from endemic areas >1%
Incarcerated people
Trans women
PWID
Partners of HIV+
Which markers are tested in HIV?
Viral RNA (pcr is expensive)
p24 (comes positive after RNA)
Antibody (only pos after 3 months/seroconversion)
When are most HIV cases tested best?
4th generation Ab/Ag laboratory test 99% sensitive at 45 days
What is a rapid HIV test?
Fingerprick blood specimen or saliva
Results within 20-30 minutes
3rd generation (Ab only) or 4th generation (Ab/Ag)
When do you treat HIV+ people?
Immediately
Don’t wait for low CD4
Define HAART
a combination of 3 drugs from at least 2 drug classes to which the virus is susceptible
test for resistnace initially
function
Reduce viral load to undetectable levels
Restore immunocompetence
Reduce morbidity and mortality
Prevets onward transmission
Rifampicin in HIV?
NO
What’s the main solution to ARV resistance?
ARV adherence
Prognosis of HIV
Young people started on HAART with CD4 >500 may have a longer life expectancy than HIV negative counterparts
Though if poorly managed people have fewer good health years
DD interactions of HIV drugs
Protease inhibitors are generally potent liver enzyme inhibitors
Some drugs require pharmacological boosting (with potent liver enzyme inhibitors)
NNRTIs are generally potent liver enzyme inducers
Some ARVs are victim to DDIs
When is someone HIV+ unable to transmit the virus?
CD4+ under 200 (lab says 30)
How do people tend to take PrEP?
Usually everyday
If sex event e.g. use in lead up and afterwards
Features of PEP
Within 72h of sexual/occ exposure
Combination ART taken for 4 weeks
Unlicensed
Prevention of vertical transmission
HAART during pregnancy
Vaginal delivery if undetected viral load
Caesarean section if detected viral load
2-4/52 PEP for neonate
Exclusive formula feeding though there are some mothers breastfeeding in Tayside under caution
What is the risk of MTCT/vertical transmission?
<1% risk of MTCT in UK/Ireland
<0.1% risk of MTCT if VL undetected at delivery
