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YEAR 5: Immunopathology > IMMUNO: Secondary immune deficiencies and HIV infection Pt.2 > Flashcards

IMMUNO: Secondary immune deficiencies and HIV infection Pt.2 Flashcards

1
Q

How long does it take for HIV to infect cells?

A

HIV provirus integrates into memory CD4 T cells within 72 hours of infection producing a long-lived reservoid of latent infection which is not responsive to ART

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2
Q

Does ART affect the latent HIV infection present in memory CD4 T cells?

A

No

  • Latent cells infected with HIV do not respond to ART
  • ART can prevent new cell from becoming infected but cannot eliminate infection once HIV-1 has integrated into host DNA
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3
Q

Describe the changes in these immune factors in the three phases of HIV infection:

  1. CD4+ T cells in blood
  2. Mucosal CD4+ T cells (including GIT)
  3. Viraemia
  4. Immune activation
A
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4
Q

What are the effects of HIV on the immune system?

A
  1. CD4 T cell depletion
  2. Impaired CD4 and CD8 T cell function
  3. Loss of antigen-specific humoral response
  4. Chronic immune activation
  5. Disruption of lymph nodes and impaired ability to generate protective T/B cell immune responses
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5
Q

What types of test are used in the diagnosis of HIV infection? Compare their uses.

A

Screening Test: Detects anti-HIV Ab via ELISA

Confirmation Test: Detects Ab via Western Blot

  • A positive test requires patient to have SEROCONVERTED (i.e. started to produce Ab)
  • This happens after ~10 weeks incubation period

HIV-1 RNA tests:

  • When negative serology + high clinical suspicion
  • In children <18m (serology not useful bc. passive transfer Abs from Mum)

Rapid point of care tests: Finger prick, 20 minutes but not sensitive

Assays to detect p24 antigen, gp41 from HIV-1 group O, gp160 envelope protein in HIV-1 and gp36 HIV-2

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6
Q

Which proteins are used in diagnostic assays for HIV-1 and HIV-2?

A
  1. HIV-1 O group = gp41
  2. HIV-1 M group = gp160
  3. HIV-2 = gp36
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7
Q

What are some HIV-1 specific-tests used after diagnosis ?

A
  1. Viral load - PCR used to detect viral RNA (very sensitive)
  2. Genotyping for drug resistance
  3. Tropism to confirm co-receptor (whether CCR5 positive - can use CCR5 antagonist)
  4. HLA-B*5701 blood test - abacavir
  5. T cell counts - CD4 T cell count via FACS (flow cytometry), used to assess course of disease, onset of AIDS, and CD4:CD8 T cell ratio
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8
Q

Deficiency of which cell receptor renders a person resistant to HIV?

A

CCR5

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9
Q

Why do HIV patients need to be tested for HLA-B*5701?

A

Risk of severe hypersensitivity to abacavir with this allele. Present in 8% of population in NW London.

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10
Q

What is the viral load set point significance? What factors affect the VL set point?

A

VL set point = the point to which, after 3-6 months of infection, the viral concentration plateaus

VL set point significance:

  • Correlates with long term outcome
  • Stratifies progression to symptomatic HIV-1 infection

VL set point is affected by:

  1. Viral genotype
  2. CD8 T cell immunity
  3. Host genetics (HLA/CCR5)
  4. Immune activation
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11
Q

As CD4 T cell count drops below 800 cells/mm^2, what infections are patients at risk of?

A
  • <800 - lymphadenopathy, thrombocytopenia
  • <500 - bacterial or fungal skin, oral, herpes simplex/zoster
  • <400 - Kaposi’s sarcoma
  • <300 - hairy leukoplakia, tuberculosis
  • <200 - PCP, cryptococcosis, toxoplasmosis
  • <100 - CMV, lymphoma
    MAC (myobacterium avium complex)

(Other slide says CD4 thresholds for PCP, toxoplasma gondii and MAC are 200, 100 and 75 x10^9 cells/L respectively)

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12
Q

What are the 5 classes of ART available in the UK? Give an example of each.

A
  1. Reverse transcriptase inhibitors - NRTI, NNRTI
  2. Boosted protease inhibitors - ritonavir + lopinavir
  3. Integrase inhibitors - dolutegravir, raltegravir
  4. CCR5 antagonists - maraviroc (rarely) used
  5. Fusion inhibitors - T20 (not used)
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13
Q

What are the 3 main uses of ART?

A

TEST AND TREAT

  • Those with active HIV-1, irrespective of CD4 T cell count

TREAT TO PREVENT INFECTION

  • Prevent transmission to seronegative partner
  • In pregnancy to prevent fetus infection

PROPHYLAXIS

  • PReP to reduce risk of acquisition
  • PEP after inadvertent exposure to HIV-1 infection following occupational exposure or after high risk sex
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14
Q

What is the first line HIV therapy regimen?

A

2 NRTI and 1 NNRTI

OR

2 NRTI and 1 integrase inhibitor

Example regimen: Emtricitabine + Tenofovir + Efavirenz (Available as 1 pill: Atripla)

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15
Q

What is the management of HIV in pregnany?

A

Zidovudine: Antepartum PO; For delivery IV
PO to newborn for 6/52 (reduces transmission from 26% to 8%)

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16
Q

What is the main reason for changes to HIV-1 therapy?

A

Drug toxicity rather than virological failure

BUT it is safer to continue ART than to interrupt the anti-HIV treatment in almost all cases (SMART study)

17
Q

Does ART reverse chronic inflammation?

A

ART does not usually reverse chronic immune inflammation which is still a risk factor for cardiovascular, liver and bone and CNS disease

BUT if they start ART before significant immune damage, they will have a similar life expectancy to seronegative controls

18
Q

How soon after stopping ART does HIV-1 become detectable in blood?

A

2-3 weeks later

19
Q

What should be monitored on ART for HIV-1?

A
  1. Compliance and side-effects
  2. Regular viral load
  3. Liver, renal, bone and lipid toxicity
  4. CD4 T cells (only if <350 cells/ul)
  5. CVD and osteoporosis risk
  6. Monitor sexual health and vaccine uptake

Should be undetectable within 3 months of starting ART

20
Q

What are vaccine trials for HIV-1 focusing on?

A

Development of neutralising and non-neutralising antibodies

Use of CMV vectors, TLR adjuvants, checkpoint inhibitors to stimulate CD8 T cell immune responses

21
Q

What are the main strategies proposed/used for HIV-1 cure?

A
  1. Allogeneic stem cell transpants from CCR-delta32 HLA matched donors (used in Berlin and London patients)
  2. Shock and Kill strategy
22
Q

A 65 year-old male with a history of steroid dependent asthma, hypertension, Type 2 Diabetes Mellitus and osteoporosis presents with recurrent chest, sinus, and skin infections. Past medical history of chemotherapy for follicular lymphoma and he has recently completed a 2 year maintenance therapy of 3 monthly rituximab. Current oral medication includes Prednisolone 5mg OD, Losartan 50mg OD, metformin500mg BD, alendronic acid 70mg weekly.

Serum immunoglobulins are as follows

  • IgG – 3.9g/L (ref interval 6.4-16.0g/L)
  • IgA – 0.9g/L (ref interval 0.8-3.4g/L)
  • IgM – 0.1g/L (ref interval 0.5-2.0g/L)
  • IgE 200IU/ml (reference interval 3-120IU/ml)

Which of the following medication are most likely to have cause antibody deficiency

  • A) Metformin
  • B) Losartan
  • C) Prednisolone
  • D) Alendronic Acid
  • E) Rituximab
A

Rituximab

23
Q

A 57-year-old male is referred to the Chest clinic with recurrent chest infections, requiring antibiotic therapy. Past medical history reveal lichen planus and a history of surgery for an anterior mediastinal mass 4 year previously. Physical examination show nail candidiasis, sternotomy scar and bi-basal crepitations. A HRCT chest scan shows extensive bronchiectasis.

Immune investigation are as follows

  • IgG – 3.1g/L (ref interval 6.4-16.0g/L)
  • IgA – 0.4g/L (ref interval 0.8-3.4g/L)
  • IgM – 0.2g/L (ref interval 0.5-2.0g/L)
  • IgE 500IU/ml (reference interval 3-120IU/ml)
  • B cell count 10cell/ul ( ref interval 100-500)

What is the most likely diagnosis?

  • A) Partial antibody deficiency syndrome
  • B) Common variable immune deficiency
  • C) High grade B cell Mediastinal Lymphoma
  • D) Thymoma with antibody deficiency/Good’s syndrome
  • E) Hyper IgE syndrome
A

Thymoma with antibody deficiency/Goods’ syndrome

24
Q

Which of the following condition are more likely to present in patients with a CD4 T cell counts of more than 350cells/ul

  • A) CMV retinitis, Toxoplasma encephalitis, visceral Kaposi sarcoma
  • B) Herpes zoster, Pulmonary Tuberculosis, Pneumococcal pneumonia
  • C) Pneumocystis jirovecci pneumonia, disseminated MAC, ITP
  • D) EBV CNS lymphoma, oral candida, cryptococcal meningitis
  • E) Cutaneous Kaposi sarcoma, disseminated MAC, HSV infection
A

Herpes zoster, Pulmonary Tuberculosis, Pneumococcal pneumonia

25
Q

Which of the following statements are true about HIV-1 infection

  • A) Reverse transcription is associated with few errors in copying HIV-1 RNA template
  • B) Preferred option to commence ART in the UK is dual combination therapy containing an integrase inhibitor and NRTI
  • C) HLA-B*5701 blood test is used to prevent hypersensitivity reaction with protease inhibitors
  • D) Residual immune activation is commonly seen in patients on suppressive ART regimens
  • E) HIV-1 serology point care tests have similar diagnostic performance to 4th generation combined p24antigen/antibody tests
A

Residual immune activation is commonly seen in patients on suppressive ART regimens

YEAR 5: Immunopathology (25 decks)

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