HIV and Secondary Immunodeficiency

Question 1

What are some causes of secondary immune deficiency?

Answer 1

1. Malnutrition
2. Drugs
3. 2nd to infections: Mesales, TB, HIV, potentialls SARS-CoV-2
4. ageing, genetic metabolic disease etc. etc.

Question 2

What are the most common drugs causing immune supression?

Answer 2

1. Steroids (Gluco + Mineralcorticoids)
2. Cytotoxic agents (MTX, azathioprine, others)
3. Calcineurin inhibitors (cyclosporine, tacrolimus)
4. Antiepileptic drugs (phenytoin, carbamazepine, levetiracetam)
5. DMARD
6. Other Biologics and Cellular therapies (e.g. JAK inhibitors: tofacitttinib, other new biologics)

Question 3

What should be co-prescribed when prescribing rituximab chemotherapy/ other anti-CD20 drugs?

Answer 3

Usually with PCP prophylaxis due to increased risk of fungal infections

Question 4

How do biological treatments (especially anti-CD20 agents) cause immunodeficiency?

Answer 4

Leading to antibody deficiency –> (increased risk of bacterial/viral/fungal infections)

Question 5

What lab tests should be done to investigate secondary immunodeficiency?

Answer 5

FISH analysis (recap)

2. FBC
3. Immunoglobulins (IgG, A M, E)
4. Serum complements (C3,4)
5. HIV test
   –> will pick up cause of 85% of immunodeficiency

Question 6

What first line chemical blood test should be done in a pateint with 2nd immunodeficiency?

Answer 6

• Renal+Liver profile (incl. urine cr ratio, albumin)
• Calcium and bone
• Serum free light chains + electrophoresis

Question 7

What does an isolated reduction in IgG suggests?

Answer 7

1. Protein loosing enteropathy
2. Prednisolone >10mg/day

Question 8

What does a reduction in IgG and IgM on serum immunoglobulins suggest?

Answer 8

Monitor for B cell neoplasm
? History of exposure of rituximab

Question 9

What might a reductionin IgG and IgA suggest?

Answer 9

? Primary antibody deficiency

Question 10

Why would you measure vaccine antibody concentration in investigation for immune deficiency?

Answer 10

Usually measure
1. tetanus toxoid protein antigen
2. Pneumovax: T-cell independent production of antibodies

Measure to see if promary antibody deficiency syndromes+ needed as criteria for replacement therapy

Question 11

What are conservative measurements to manage secondary immune deficiency?

Answer 11

• reduce exposure to infection
• immunisation + immunisation of household contacts

Question 12

What is medical management of secondary immune deficiency?

Answer 12

1. Early + longer ABx treatment of bacterial infection
2. Prophylactic ABx
3. Potentially IgG replacement therapy

Question 13

What are the criteria for IgG replacement therapy in secondary antibody deficiency syndromes?

Answer 13

Question 14

What is the difference between HIV 1 and HIV 2?

Answer 14

HIV1 : most common species worldwide
HIV-2: restricted almost completely to West Africa –> slightly less transmission and slower progression

Question 15

What are the key characteristics oft the HI-virus?

Answer 15

• double-stranded RNA virus
• retrovirus –> integration into host genome

Question 16

What are the effects of untreated HIV infectionon in the lymph nodes?

Answer 16

Disruption of lympho node architecture + impaired ability to generatet protective T cand Be cell immune response

Question 17

Explain the natural progression of HIV infections regarding
1. Viral load
2. CD4 counts
3. Immune activation

Answer 17

Usually acute infection followed by chornic phase (~10 years)
10% are rapid progressors (2-3 years)

1. Viral Load: Very high in acute infection (2-14 weeks post-transmission), then decreases in latent phase and increases again in AIDS
2. CD4 counts: small dip initially, but then recovers and only dips in AIDS/ symptomatic chronic period

Question 18

How is HIV testes for?

Answer 18

Now Screening with
4th generation combined HIV-1 antibody/antigen test
(positive 1 month post-aquisition)
(others are also possible: e.g. Viral RNA, rapid point of care testing)

Viral RNA testing if

• negative test but high clinical suspicion
• in babys under 18 months due to AB transfere from mother

Followed by confirmatory testing if positive
* Repeat 4th generation test
* do HIV 1/2 differentiation immunoassay

Question 19

What are the main characteristics of an acute HIV infection?
1. Clinically
2. Bloods (RNA;, CD4 and CD8 counts)

Answer 19

1. Clinically: flu like symptoms (in 70%), lymphadenopathy, rash, GI symptoms

Bloods:
- RNA: very high (high risk of transmission)
- CD4 decrease
- CD8 increase (coincides with drop in Viral load)

Question 20

What baseline investigations should be done in a patient just diagnosed with HIV?

Answer 20

+ HIV Viral load and HIV genotypes (next generation sequencing)
+ T-cell count (CD4 cound and CD4 : CD8 cell ratio)

Question 21

What diseases are you predisposed to with a CD4 count <500?

Answer 21

Bacterial Skin infections
HSV Zoster
Fungal infections (skin, oral)

Question 22

What diseases are you predisposed to with a CD4 count <400?

Answer 22

kaposi’s sarcoma

Question 23

What diseases are you predisposed to with a CD4 count <300?

Answer 23

Hariy Leukoplakia
Tuberculosis

Question 24

What diseases are you predisposed to with a CD4 count <200?

Answer 24

PCP/PJP
Cryptococcis
Toxoplasmosis

Question 25

What diseases are you predisposed to with a CD4 count <100?

Answer 25

CMV
Lymphoma (EBV)

Question 26

Explain the principles and treatment regiment for HIV infection

Answer 26

Initiation of treatment on triple therapy

Triple therapy
* Two NRTI + 3rd drug of a different class, e.g.
* (usually protease inhibitor or NNRTI)