Term
| Describe the structure of the HIV virus. |
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Definition
lentivirus from retrovirus family
ssRN
reverse transcriptase
gycoproetin envelope - gp120/gp41 |
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Term
| What are the 2 types of HIV virus? |
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Definition
HIV 1
Maj subtypes = 10 subtypes - B common in europe
Outliers - highly divergent, confined to cameroons
HIV 2
less virulent
confined to west africa |
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Term
| Descirbe the pathogenesis of HIV |
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Definition
- gp120 recognised by CD4 cells
- Interaction of gp120 and CD4 + co-stimulation from gp41 = receptor fusion
- Entry of HIV into host cell
- ssRNA relased into cytoplasm and Rev transcriptase makes ssDNA
- Cellular polymerase created dsDNA = converted into host genome
- Replication of viral DNA uses host mechanisms
- budding of new viruses
- destruction of host cell |
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Term
| Why is the infection of macrophages clinically important in HIV? |
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Definition
Infection of macrophages creates a protected virus factory as cannot be destoryed by host mechanisms.
Macrophages can also migrate and spread virus
CNS invasion = damage by cytokine production and microglia have CD4 so get infected. |
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Term
| What are the routes of transmission of HIV? |
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Definition
1. SEXUAL INTERCOURSE
- vaginal/anal/oral
- males to females most common
-spread enhanced by STDs (ulceration)
2. VERTICAL TRANSMISSION
- from mother during pregnancy/labour/breastfeeding (20%)
- inc risk if: high maternal viral load/premature rupture of membranes
3. CONTAMINATED BLOOD/B.PRODUCTS/ORGANS
- in countries where screening is poor
- in uk pre 1985
4. CONTAMINATED NEEDLES
- needle stick injury (0.3% risk)
- IVDA's sharing needles |
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Term
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Definition
1. Detection of Anti-HIV antibodies
2. Direct identification of virus material
=ELISA then Western Blot if +ve |
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Term
| What is important to consider when testing for HIV? |
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Definition
| Can take 3wks-3month for viral antibodies to be detected (Seroconversion) but patient is still infected as has high viral load and can still infect others. |
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Term
| What markers are used to monitor HIV infection? |
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Definition
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Term
| What are the 4 clinical stages of HIV infection |
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Definition
1.Infection/seroconversion
2.Assymptomatic/clinical latency
3.Symptomatic disease
4.AIDS |
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Term
| Describe the 1st stage of HIV infection |
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Definition
INCUBATION/SEROCONVERSION
rapid viral replication in all organs
immune response = increased CD8
50% assymp
50% generalised lymphadenopathy/malaise/headache/sore throat. self limiting - clears within 3 weeks. |
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Term
| Describe the 2nd phase of HIV infection |
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Definition
ASSYMPTOMATIC/CLINICAL LATENCY
virus replication continues
antibodies seen
can persist for up to 10yrs
persistant generalised lymphadenopathy
cd8 inc
cd4 compensated for initally, then declines |
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Term
| Describe the 3rd phase of HIV infection. |
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Definition
Think "SPOON XC"
Seborrhoeic dermatitis
Persistant Generalised Lymphadenopathy
Oral hairy leukoplakia (EBV)
Oesophageal candidiasis
Night Sweats
Xeroderma
Cotton wool spots on retina (HIV ab-AG deposition) |
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Term
| Describe the 4th stage of HIV infection |
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Definition
AIDS
terminal phase
get aids defining conditions
pheumocystis canarii pneumonia
toxoplasmosis of brain
CMV retinitis
kaposis sarcoma
burkitts lymphoma
mycobacterium tuberculosis/avium infection |
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Term
| How can HIV be prevented? |
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Definition
Safe sex
dont share needles/needle exchange
ARV's to HIV mums
screen blood products
partner notification |
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Term
| What class of medications are used to treat HIV? Are there any problems with these? |
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Definition
HAART = Highly active antiretroviral therapy.
Aims to significantly suppress viral replication for as long as possible.
BUT
-does not eradicate (pt still infectious)
-if dtop, get rebound inc in viral load |
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Term
| What are the 2 classes of drugs that make up HAART? |
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Definition
1. Reverse transcriptase inhibitors
2. Protease inhibitors |
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Term
| How do reverse transcriptase inhibitors work? |
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Definition
1. NUCLEOSIDE ANALOGUES
bind to viral RNA and act as DNA chain terminators
2. NON-NUCLEOSIDE RTI's
bind directly to enzyme and interfere with action
-skin rash
-liver disturbance
3. NUCLEOTIDE ANALOGUES
-not yet in uk
-competitve inhibitors of RT
-no liver effects |
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Term
| How do prtoease inhibitors work? |
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Definition
act on HIV aspartyl protease
-involved in production of viral proteins
= distrbed viral maturation
BUT - disturbed fat metabolism and alter CYP450 |
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Term
| Why is adherance to drug therapy important? |
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Definition
Otherwise get resistance to drug
resistance to multiple classes |
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Term
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Definition
= Post Exposure Prophylaxis
=2 nucleoside analaogues and a protease inhibitor for 4 weeks.
do serum save |
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