HIV/AIDS Flashcards
What are the methods of HIV prevention?
- Antiretroviral treatment (ART; prevention or pre/post-exposure prophylaxis)
- Condom use
- Male circumcision (decreases transmission to men)
What is the U=U campaign?
undetectabl=untransmittable (treatment is prevention; it can reduce transmission by up to 96%)
What is PrEP?
Pre-exposure prophylaxis
Daily oral antiretroviral combo pill
What tests detect HIV infection? (earliest possible to latest)
- HIV RNA NAAT (nucleic acid amplification test)
**detects as early as 10 days - 4th/5th gen Ab/Ag test (detect both the p24 antigen and HIV antibody) **detects as early as 14 days
- ELISA
- Western blot
Describe HIV transmission
- Occurs at a mucosal surface (vaginal/rectal)
- Virus crosses mucosal surface and infects CD4+ T cells, DCs, and macrophages
- Small foci of infection are established locally and then expand/disseminate through lymph and blood
What is the DC role in responding to HIV infection?
Initial surge of IL15/IFNs
What is the NK cell role in responding to HIV infection?
- NKs activated by IFN-1, IL-15, IL-18, and receptor/ligand interactions
- Lyse malignant or infected cells (via perforin/granzyme, fas ligand mediated apoptosis, ADCC)
- Produce antiviral factors (IFNγ, TNFα, β-chemokines)
What is the B cell role in responding to HIV infection?
Initial Ab response to Env protein, but is non-neutralizing
Neutralizing Ab response develops too slowly (~12 weeks) to be effective
What is the T cell role in responding to HIV infection?
- First HIV specific CD8+ T cell responses are seen as viremia peaks, initially specific for Env and Nef
- Virus sequence changes with rapid selection to escape
- Eventually T cells become more targeted to conserve epitopes
**“Immune system is always one step behind HIV mutations”
What genetics can help individuals control HIV?
- Certain MHC class I alleles are associated with control of viremia
- Certain NK receptors have been associated with delayed progression to AIDS
- “Elite controllers” may have more functional CD8+ T cells (i.e. more perforin, granzyme, and cytokine production)
Do we need an HIV cure?
Yes,
even when viral loads are suppressed ART doesn’t fully restore normal health and immune dysfunction,
and cost/access to meds is still a barrier for many HIV infected individuals worldwide
What causes the persistent inflammation and immune dysfunction even in patients suppressed by ART?
- ongoing HIV replication
- infection with co-pathogens such as CMV
- dysfunctional immunoregulatory factors
- microbial translocation
- lymphoid fibrosis
What leads to microbial translocation?
Breakdown in tight junctions, loss of immune cells (Th17), and alteration of gut flora
What is microbial translocation?
The passage of viable bacteria from the GI tract to extraintestinal sites, such as the liver, spleen, kidney, and bloodstream.
**Results in increased immune activation, inflammation, and collagen deposition in lymphatic tissue
What cells harbor the latent HIV reservoir?
Long-lived memory CD4+ T cells (HIV integrates into DNA)
**established very early in the HIV infection; early treatment can limit the size of the reservoir
