HIV Flashcards
What is the most common group of HIV seen?
HIV-1 > HIV-2 (west Africa and East London)
HIV-1 Group M (Major) is most common, 95% cases
3 major structural genes of HIV genome
HIV genome
3 major structural genes
Gag - nuclear proteins
Pol - viral enzymes ( Reverse transcriptase, Integrase, Protease)
Env - envelope glycoproteins
Why does drug resistance occur rapidly in HIV?
1-10 billion virions/ day, highly error prone bc no proof-reading mechanism
1 mutation/ new virus, virus rapidly forms quasi-species
Rapid selection of virus with survival advantage is resistant to drugs
Drug resistance is archived but can be transmitted – if exposed to similar drug resistant too, same thing can happen and will become resistant to that
What is the immune response to HIV?
B cells produce neutralising antibodies, directed against gp-120 (anti-gp120 antibodies) docking protein, check this on antibody test
T cell Cd8+ cytotoxic response, HIV specific CTL response
Progressive damage to immune system reduces the ability to clear viru
how does HIV enter CD4+ cells?
HIV entry into CD4 cells
- GP120 mediates target recognition
- gp41 mediates fusion
- After gp120 binds to CD4, it breaks away exposing the hydrophobic tip of gp41
- gp41 is ‘buried’ deeply in the lipid membrane of the target cell
- Virus particle is drawn close to the cell surface, facilitating fusion
where are CCR5 and CXCR4 found? what type of virus preferentially binds?
CCR5 - on macrophages
macrophage-trophic viruses bind
CXCR4 - on T cells
lymphotrophophic virus bind
when are CCR5 and CXCR4 dominant?
CCR5 dominant in early infection
CXCR4 – predominant later, associated with disease progression
what gene mutation can give HIV immunity?
CCR5 delta 32 (D32/D32) homozygous –> deletion mutation in CCR5 co-receptor, HIV cannot bind –> naturally resistant to HIV infection
- Occurs in 1% of Europeans
what is immune response to HIV?
HUMORAL:
- B-cells produce neutralizing antibody (post-acute HIV infection)
- All patients, anti-gp120 Ab
BUT…Fails to clear the virus
CYTOTOXIC:
- CD8+ cells produce HIV specific CTL (cytotoxic lymphocytes) response
- Can control HIV replication in early infection
BUT…overcome by progressive damage to immune system
o Inverse relationship between viral load and HIV-specific CT
best marker to predictor outcome in untreated HIV
• Viral load better than CD4 count to
predict outcome in untreated HIV
Why are HIV+ patients more at risk of infections?
• Defective cell-mediated immunity
– Defective cytokine production resulting in poor stimulation of cytotoxic T cells
– So cant deal with intracellular organisms = salmonella
• Reduced antibody production
• Neutropenia
– HIV, drugs, other infections
• Other
– IVDU
– Indwelling lines
– Exposure to hospital acquired pathogens
What are the difficulties in treating opportunistic infections In HIV?
• Drug toxicity – High doses – Extended treatment time – Multiple drugs • Parenteral therapy • Polypharmacy side effetcs • Drug resistance • HAART is key to survival – Risk of IRIS following HAART – Drug interactions
How you prevent opportunistic infections In HIV?
• Early HAART, prevent immunosuppression
• Primary prophylaxis
– Prevents infection or reactivation of infection when CD4<200
– Septrin for PCP
• Secondary prophylaxis
– Prevents relapse of treated infection until CD4 count increased after HAART
– Can stop 2y prophylaxis when CD4 count shows a sustained raise on ART
• Vaccination
– May be ineffective at low CD4 if <200
What are the differences in presentation of MTB and MAI infection in HIV?
MTB = mycobacterium tuberculosis MAI/MAC = mycobacterium avium intracellular
MTB MAI
Re-activation of old infection New infection? via drinking water/showering
Occurs early in HIV disease Occurs late in diseaseCD4 <100
Usually involves chest Usually involves GIT (especially jejunum), hepatomegaly,
(raised ALP), abdominal lymph-adenopathy and anaemia
Responds quickly to treatment Responds slowly over 3-4/52
May form granuloma
What is the importance of malignancy in HIV?
Malignancies now most common cause of death in HIV patients
Shift from AIDS-defining cancers to non-AIDS-defining cancers:
Not associated with CD4 counts
Incidence not reduced by ART • Overall risk doubled with HIV infection • Multiple risk factors: – Immunosuppression • Risk increases with falling CD4 count • Nadir CD4 significant • Earlier HAART may reduce life-long risk • HAART has altered spectrum of disease – Co-infection, cancer is often virus-driven • EBV, HPV, HHV-8, HBV, HCV – Lifestyle • Smoking, alcohol – Aging • Not all malignancies are AIDS-defining
