HIV

Question 1

Describe the process by which HIV enters cells

Answer 1

1. Receptor binding - gp120 binds CD4
2. Co-receptor binding - gp120 binds CXCR4/CCR5
3. ssRNA released into infected cell, RT forms ssDNA then dsDNA
4. dsDNA integrated into host DNA
5. Viral proteins transcribed, assembled into viruses and released from host cell

Question 2

Cells affected by HIV

Answer 2

CD4+ T cells
CD4+ dendritic cells
CD4+ monocytes

Question 3

HIV structure

Answer 3

ssRNA (diploid - 2 copies - 9 genes encoding 15 proteins) + RT + p7/p9 proteins
All contained in p24 capsid
Surrounded by cell membrane containing gp120 and gp41

Question 4

env gene

Answer 4

Encodes gp120

Question 5

pol gene

Answer 5

Encodes RT

Question 6

Effect of HIV on CD4+ cells

Answer 6

Decline in CD4+ function
Infected CD4+ killed by CD8+ cells + disabled
= Loss of T cell memory, failure of B cell activation, failure of CD8 activation (hence drop after acute phase)

Question 7

Acute phase HIV infection

Answer 7

Lasts ~12w with seroconversion at 10w
Non-specific fever like symptoms
Spike in viral load and CD8+ before stabilising, dip in CD4+
Innate response within hours
Adaptive response takes longer:
- Neutralising gp120 + gp41 antibodies
- Non-neutralising p24 antibodies
- CD8 produce MIP-1a, MIP-1b + RANTES chemokines to block HIV fusion

Question 8

CD4 200-500

Answer 8

Swollen LNs, minor infections (Oral Hairy Leukoplakia, Oral Candidiasis)

Question 9

CD4 <200

Answer 9

AIDs defining illnesses

PCP, Candidiasis of oesophagus, Kaposi’s (HHV8)

Question 10

What are the 3 patterns of HIV progression?

Answer 10

Typical progressors (AIDS in 8-10y) - 85%
Rapid progressors (AIDS in 2-3y) - 10%
Long-term non-progressors (AIDs in >15y) - may be due to HLA host factors or viral factors

Question 11

Rapid HIV testing

Answer 11

Fingerprick sample
Takes minutes
Looks for Anti-HIV Ab

Question 12

Fourth generation combined testing

Answer 12

Blood sample
Takes a few days
Looks for anti-HIV Ab + p24 antigen using ELISA
-> Followed up with anti-HIV Ab Western Blot to confirm

Question 13

Ix after diagnosis

Answer 13

Viral load using PCR
CD4 using FACS
Resistance testing

Question 14

Naturally occurring cytokine that inhibits HIV fusion to CD4+

Answer 14

MIP-1

Question 15

Effects of HAART

Answer 15

Suppresses viral replication
Raises CD4+ levels
Improves immune function (fewer opportunistic infections + deaths)
BUT it doesn’t eliminate HIV completely as there is a reservoir in resting T cells

Question 16

Nucleoside/nucleotide analogues
Nucleosides require phosphorylation
Inhibit reverse transcriptase

Answer 16

NRTIs (e.g. nucleosides - zidovudine, abacivir, emtricitabine / nucleotides - tenofovir, truvada)

Question 17

Not nucleoside analogues

Bind p66 site and block reverse transcriptase by causing conformational change

Answer 17

NNRTIs (e.g. efavirenz, nevirapine)

Question 18

Bind viral proteases neccessary for virus replication and assembly

Answer 18

Protease inhibitors (-navirs)

Question 19

HAART

Answer 19

2 NRTIs, 1 NNRTI, boosted PI

Question 20

HIV in pregnancy

Answer 20

Zidovudine (NRTI)
PO ante-natal
IV at delivery
PO to bewborn for 6w
Don't breastfeed

Question 21

Side effects of anti-HIV

Answer 21

Anaemia
Neutropenia
Hepatic + cardiac dysfunction
Myopathy