HIV and AIDS

Question 1

Describe HIV structure

Answer 1

Positive stranded RNA virus
Two dimerised RNA strands - dimeric structure essential for replication and stabilisation

Question 2

How many people have HIV in the UK?

Answer 2

100,000 people

Question 3

What are the lineages of HIV?

Answer 3

HIV 1 comprised of four lineages: M,N,O and P
HIV 2 has eight lineages A-H

Question 4

What are the main differences between HIV 1 and 2?

Answer 4

HIV 2 = lower transmissability and reduced likelihood of progression to AIDS
HIV 2 = has lower plasma viral loads
HIV 2 = lower levels of immune activation however more IL-2
Immune response to HIV 2 is more protective against progression

Question 5

What are the stages of transmission of HIV?

Answer 5

1) Bind to CD4 on Th, Treg, monocytes, macrophages, DCs
2) To enter cell, requires coreceptors CCR5 and CXCR4 that binds to CD4
- CCR5 on T cells, GALT, macrophages, DCs, microglia
- CXCR4 on T cell, B cells, neutrophils, eosinophils

Question 6

What is the first stage of progression of infection of HIV?

Answer 6

Eclipse phase:
- Infection of first cells
- systemic spread via lymph nodes
- interferon response
- viral reservoir established
- GALT destruction

Question 7

What is the second stage of progression of infection of HIV?

Answer 7

Acute phase:
- First detection in blood
- Flu-like symptoms
- CTL response
- Seroconversion (binding antibodies)

Question 8

What is the third stage of progression of infection of HIV?

Answer 8

Chronic phase:
- Viral set point establishes
- Progressive CD4+ T cell loss
- Chronic inflammation
- Progression to AIDS

Question 9

What are the main routes of transmission of HIV?

Answer 9

• Unprotected sexual intercourse with infected partner
• Vertical transmission (mother>child: in utero, during birth, breastmilk)
• Injection drug use

Question 10

What is the interaction between HIV and the immune system?

Answer 10

• Antigen specific T cell response to HIV infection will contribute to the control of viral replication
• But HIV selectively infects active CD4 T cells, so increased active T cell levels accelerate viral replication and CD4 T cell depletion
• Untreated HIV 1 depletion of CD4+ T cells which mostly expresses CD127 on a chain of IL7 receptor occurs
• IL7/IL7R signalling essential for further transmission of CD4+ T cell effector to memory

Question 11

How is HIV diagnosed?

Answer 11

Full and differential blood count
- to measure viral load and target cell levels (CD4 and CD8)

Question 12

When does AIDS occur?

Answer 12

When CD4 cell count falls below 200 cells/mm3: makes a person vulnerable to opportunistic infections and AIDS-defining conditions e.g. TB

Question 13

What are a few examples of chronic co-morbidities of HIV/AIDS?

Answer 13

Invasive cervical cancer
Kaposi sarcoma
HIV wasting syndrome

Question 14

What are a few examples of common co-infections of HIV/AIDS?

Answer 14

TB
Oesophageal candidiasis
HSV encephalitis

Question 15

How is HIV managed?

Answer 15

Antiretroviral chemotherapy

Question 16

What drugs are used in antiretroviral chemotherapy?

Answer 16

Emtricitabine
Tenofovir
Atazanavir
Rilpivirine

Question 17

What type of drug is emtricitabine and its target?

Answer 17

Type: nucleoside reverse transcriptase inhibitor (NRTI)
Target: it is cytidine analogue. HIV reverse transcriptase, preventing transcriptase, preventing transcription of HIV RNA to DNA

Question 18

What type of drug is tenovir and its target?

Answer 18

Pro-drug
Reverse transcriptase inhibitor
Target:
activated by bi-phosphroylation and acts as antiviral acyclic nucleoside phosphonate

Question 19

What type of drug is atazanavir and its target?

Answer 19

Protease inhibitor
Target:
HIV-1 protease is an enzyme required for the proteolytic cleavage of the viral polyprotein precursors into the individual functional proteins Atazanavir binds to the protease active site

Question 20

What type of drug is Rilipivirine and its target?

Answer 20

Non-nucleoside reverse transcriptase inhibitor (NNRTI)
Target:
Diarylpyrimidine derivative and acts to inhibit HIV reverse transcriptase inhibitor

Question 21

What are HIV reservoirs in the body?

Answer 21

T follicular helper cells and follicular dendritic cells = long liver viral reservoirs in B cell follicles (BCF) in secondary LTs: Spleen, GALT, mesenteric lymph nodes, peripheral lymph nodes
Has low cell activation and residual levels of immune activation and immune mediators

Question 22

What is the effect of ART on HIV reservoirs?

Answer 22

Increases cell activation, levels of immune activation and immune mediators
Drug penetration is very heterogenous - can allow intermittent viral replication