HIV Flashcards
What three genes define a retrovirus?
Gag
Pol
**
Primary Infection cell entry?
Virus targets CD4 cells, macrophages and dendritic cells
Can also invade mucosa
GP120 binds to CD4 receptor and appropriate co-receptor CXCR4 or CCR5
GP41 promotes fusion of viral and cellular membranes
How does HIV integrate genetic material?
Reverse transcriptase copies viral RNA into double stranded DNA
This is site of action for NRTI (AZT, 3TC, D4T etc) and NNRTI (NVP, EFZ)
CDNA enters cell nucleus and integrates into human DNA- this is site of action for integrate inhibitors
What is transcription?
When an infected cell is activated, viral replication begins
Tat and rev genes get activates
Tat amplifies transcription of RNA
Rev promotes RNA transport to cytoplasm
What is translation?
Other viral proteins are translated and new viral particles assembled
Protease inhibitors act at this level
What is defined as AIDS?
When CD4 <200 or <14%
What is the reservoir for HIV?
Lymphoid tissue
95% of plasma detectable virus is derided from the activated infected cells
ARV cannot eradicate all infected cells
Who is screened for HIV?
High risk groups: prisoners, IVDU, MSM, sex workers
Healthcare workers
What is ELISA of HIV?
ELISAs now on 4th generation
Capacity to detect Ag (p24) and antibodies simultaneously
Can now detect HIV in acute symptomatic phase
When can you detect viral load?
11-12 days
When can you do an ELISA?
in 3-4 weeks
When do you do RNA testing?
To differentiate between HIV-1 or HIV-2
What % women or girls make up people living with HIV globally?
54%
What countries of world are women disproportionately affected?
Eastern and Southern africa, but problem globally
How many cases of HIV in children are due to transmission vertically?
> 90%
How is HIV transmitted maternal to child?
In utero: likely due to disruption of placental integrity and placental inflammation also genital tract infections
Intrapartum: Exposure of neonatal membranes to viremic body fluids, microtransfusions and any VD with instruments
Postpartum: Not fully understood, likely earlier in breastfeeding
When does HIV vertical transmission commonly occur?
Mostly in third trimester and during delivery
Main risk factors for vertical transmission?
Mainly maternal HIV viral load
New maternal HIV infection during pregnancy, likely related to higher plasma viral load levels
Other risk factors include; maternal STIs, Anaemia etc
How to prevent vertical transmission?
ALL pregnant women need HIV, Syphillis and HBsAg in first trimester
High burden settings, women should get testing in 3rd trimester and consider Postpartum period testing
Can offer Prep to serodicordant couples during pregnancy and/or postpartum.
This typically is Tenofovir disproxil fumerate (TDF) or dapivrine ring
How much do you want to reduce maternal viral load to reduce risk of vertical transmission?
You want <1000 copies/ml
Ideally lower viral load before pregnant
ART can reduce vertical transmission to <1%
What is choice of ART to prevent vertical transmission?
2 x NRTI and 1x Integrase Inhibitor
Dolutegravir, Tenofovir, lamivudine or emtricitabine
You can keep women on their orginial ART combo
Risk of using Dolutegravir in pregnancy
Neural Tube defects, but this is minimal
Benefit far outweighs the risk and is preferential over efavirenz
Do you alter mode of delivery to prevent VT?
Vaginal delivery perfectly safe
Only offer C-section in developed countries if VL>1000 copies
When do you start infant prophylaxsis?
Ideally within 6hrs of birth
Type and duration will be a risk assessment