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MD1 - Intersystems > 3. HIV 2 > Flashcards

3. HIV 2 Flashcards

1
Q

What are the progression of untreated HIV over years?

A
  • Primary infection 0-9 weeks
  • Asymptomatic infection/clinical latency = 9 weeks ~ 7 years
  • Symptomatic infection and AIDS = 7 years onwards
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2
Q

What happens in acute HIV infection?

A
  • Rapid and massive loss of CD4+ T cells.
  • > 60% mucosal T-cells die (resting and activated CD4+ CCR5 memory)
  • Massive T-lymphocytes in GALT
  • Initial decline in HIV due to CD4 substrate exhaustion
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3
Q

What is the symptoms of primary HIV infection?

A

Transient CD4 deletion and fever, myalgia, nausea, rash, malaise. pharyngitis, oral thrush, meningitis etc

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4
Q

What is the incubation period of primary HIV infection?

A

2-4 weeks

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5
Q

Does acute seroconversion occur?

A

yes in 50-95% cases

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6
Q

When does HIV RNA start to become detectable?

A

1-18 days of infection?

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7
Q

What is the immune response to HIV?

A
  • after virus dissemination body starts to make free gp41-specific non-neutralizing IgM antibody.
  • The virus escapes from CD8 T cells and just keeps escaping virus specific neutralizing antibody.
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8
Q

Why are antibodies ineffective against HIV?

A
  • Because of the high levels of Env glycosylation

- Virus also sheds free monomers of gp120

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9
Q

What are the mechanisms that allow HIV to escape the immune system?

A
  • Sequence variation (high mutation rate and high replication)
  • Exposed antigen are highly glycosilated
  • Altered antigen presentation (downregulation of MHC1 by Tat, Vpu and Nef
  • Loss of effector cells (clonal exhaustion, loss of CD4 help and apoptosis)
  • Latency
  • Privileged sites (brain)
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10
Q

At what level is the viral load undetectable?

A

-

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11
Q

What are the causes of T cell depletion?

A

CD4+ T cell destruction and Chronic immune-activation

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12
Q

How does HIV destroy CD4+ t cells

A
  • Direct destruction of infected cells
  • Indirect destruction of uninfected cells
    1. Cytolysis by HIV-specific CTL or NK cells
    2. Incorporation into synctitia (fused cells)
    3. Immune activation of CD4 and CD8 T cells
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13
Q

How does HIV cause chronic immune-activation that deplete T cells?

A
  • Destroy gut mucosal barrier so that microbial products leak into systemic circulation
  • Immune system stimulated through TLR receptor
  • Elevation of pro-inflam cytokines
  • CD4+ T cells enter cell cycle and die
  • CD8+ T cells become trapped in lymph nodes
  • B cells make auto-Ab
  • Also caused impaired T-cell production
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14
Q

What are the effects of HIV on Neutrophil?

A

Reduced killing of bacteria

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15
Q

What are the effects of HIV on B cell?

A
  • General increase in antibodies
  • Autoantibodies
  • Poor response to vaccines
  • Reduced killing of encapsulated bacteria
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16
Q

What are the effects of HIV on Macrophage?

A

Reduced phagocytosis, chemotaxis and killing

17
Q

What are the effects of HIV on NK function?

A

Reduced function

18
Q

At what CD4+ level do opportunistic infections occur?

A

200 CD4+ T lymphocytes/mm3

19
Q

What are some of the opportunistic infections related to AIDS?

A
  • Pneumocystis jirovecii Pneumonia (PCP)
  • Oral infection Candida albicans
  • Hairy leukoplakia (EBV reactivation)
  • EBV Primary CNS lymphoma
  • CMV in retina
  • Cachexia
  • Kaposi’s sarcoma (HHV-8)
20
Q

What is the median surival time after

A

3.7 years

21
Q

What is the median survival after AIDS?

A

1.3 years

22
Q

What is the median CD4 at AIDS?

A

65 cells/mL

23
Q

What co-infection actually protects against HIV?

A

GBV-C (Hep G)

24
Q

What genetic mutation protects against HIV?

A

Homozygous for CCR5-D32 mutation, slowed progression if heterozygous

25
Q

What is the daily rate of viral turnover?

A

1 - 10 billion particles per day

26
Q

What is the rate of mutation?

A

1:10,000

27
Q

What is the mechanisms for persistent production of HIV?

A
  • Latency in CD4+ T cells
  • Persistent infection of hematopoietic stem cells (long-lived or replicating shielded from immune response)
  • Sanctury (brain, testis, gut)
28
Q

What is PrEP?

A

Antiretroviral agents used by HIV negative people to reduce their risk of acquiring HIV infection

29
Q

What is the most effective biomedical intervention strategy?

A

Immediate ART for positive partner

30
Q

What are some antiretroviral agents?

A
  • Tablets (Tenofovir/Tenofovir + Emitricitabine)
  • Vaginal rings or gel
  • Long acting muscular injections

MD1 - Intersystems (7 decks)

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