HIV - Part 2 Flashcards
How many people have acquired HIV-1 in the last 40 years?
75 million
HIV is a member of the which family?
Lentivirus family
Double stranded RNA virus
How does the HIV get in?
Binds to CD4 then to the chemokine co-receptor CCR5 and CXCR4
CCR5 more common
How does the retrovirus replicate?
Retroviral transcriptase
Viral enzyme integrase
see lecture slide
How many lineages of HIV? Where did they come form? When was the initial transmission? Which lineage is the current pandemic?
4 - MNOP
MNO - chimpanzees
OP - gorillas
Initial transmission of M subtype to humans occured in SE Cameroon between South east Cameroon - 1910
M is the pandemic
How long is the acute phase?
3-6 months
What happens after the 6 month acute phase? What happens to the risk of transmission during this asymptomatic phase?
Asymptomatic phase - risk of transmission is low
Heterosexual cases
With the progression of disease, you have enormous viral diversity as the viral load increases, as HIV is very bad at replicating itself accurately. Hence the need for combination therapy.
Viral quasi species
Viral mutation -
Integration of HIV provirus within CD4 cells within 72 hours leads to lifelong memory???
From the POV of the T cell
Describe CD4+ T cell response to HIV
In tissues, the mucosal CD4 t cells have a profound drop during the acute phase and do not recover afterwards
The CD 4 T cell in teh blood counts in the blood drop, then recover, then drop again over teh asympatomatic period
IgM is created in the acute phase
Neutralising antibodies is created late, by which point the strain of HIV has diversified
A good b-cell response
Complements bring down the viral load
Features of untreated HIV immunology
CD4 t cell depletion
Chronic immune activation
Impairment of CD4 and CD8 T cell function
Disruption of lymph node archtecture and impaired ability to generate protective T
Which antigens are detected
assays detect p24 antigen, gp41 from HIV1 group O
gp160 - HIV-1 M and gp36 HIV2
What comorbidities would you check for when someone is diagnosed with HIV-1?
TB
GORD
DM
BP
Hepatitis B and C
Anxiety
Depression
Baseline investigations
FBC
tb
cxr????????
HIV-1
HIV-1 genotype to look for drug resistance
HIV-1 tropism to confirm co-receptor use in
When do we use anti-retroviral therapy?
Test and treat
to prevent infection - offer to seronegative partners
In pregnancy to prevent transmission to fetus
PreP or PEP
Combination of ART
non-nucleotide reverse transcriptors
ART
prevents new cells becoming infected but cannot eliminate infection once the HIV has integrated itself into host DNA
If ART is stopped, when can HIV be detectable in the blood?
2-3 weeks as
new subcut drugs
Capsid inhibitor lenacapavir
Attachment inhibitor - fostemavir
Monitoring on ART
monitor liver, kidneys, bone and lipid toxicity
If CD4 cell counts less than 300, what kind of TB do you get?
Pulmonary if over 300
Less than 300 - Milliary