HIV infection and secondary causes of immunodeficiency

Question 1

classification of immune deficiencies

Answer 1

far more common than primary immune deficiencies

malnutrition (most common around the world)

ID: HIV

environmental stress

age extremes: prematurity and old age

surgery and trauma splenectomy

immuno suppressive drgs

genetic and metabolic diseases

Question 2

immune deficiencies exhibit diverse clinical features (4)

Answer 2

infections = severe, persistent, recurrent, unusual

autoimmune conditions (cytopaenias very common in 1o and 2o immune deficiencies) and allergic disease

persistent inflammation

cancer (viral associated EBV, HHV-8)

Question 3

common causes of 2o immune deficiencies

Answer 3

malnutrition (common cause WW)

measles = immune defect lasts months to years, increased morbidity and mortalitty

TB = inflammatory immune re-constitution syndrome

HIV = residual immune dysfunction persists despite successful ART

SATS-CoV-2 infection = multi-factorial causes, virus, drugs, co-morbidities (renal disease and DM)

Question 4

types of drugs that cause immune deficiency

Answer 4

small molecules

• glucocorticoids and mineralocorticoids
• cytotoxic agents: methotrexate, mycophenolate, cyclophosphamide and azathioprine
• calcineurin inhibitors: cyclosporine and tacrolimus
• antiepileptic drugs: phenytoin, carbamazepin, levetiracetam
• DMARD: sulphasalazine, leflunomide

JAK inhibitors

• tofacitinib, upadacitinib, ruxolitinib

Question 5

note done biologics and cellular therapies causes of immune deficiency

Answer 5

biologics = anti-CD20, anti-TNF-a protein and receptor antagonists

cellular therapy = anti-CD19-/Tc therapy

• Antibody deficiency and bacterial/viral infections are observed with rituximab and other anti-CD20 agents
• Risk of infection increased with repeated courses and in patient in patients

Question 6

haematological cancers as causes of 2o immune deficiency

Answer 6

B and plasma cell cancers (antibody deficiency syndromes are most common)

chemo, biological therapy, radiotherapy

Bc lymphoproliferative disorders

• Multiple myeloma
• CLL
• NHL
• monoclonal gammopathy of uncertain signficance

Good’s syndrome (thymoma and antibody deficiency)

• T and B cell (absent) defect
• CMV PJP and muco-cutaneuous candida
• Autoimmune disease (Pure red cell aplasia, Myasthenia gravis, Lichen planus)

Question 7

evaluation of secondary immune deficiency: question to ask in history

Answer 7

Question 8

FISH for an immunodeficiency

Answer 8

FBC

• Hb <10g/L
• neutrophil count
• lymphocyte count
• platelet count

Immunoglobulins (IgG/A/M/E)

Serum complement (C3,C4) = for serum complex disease, lupus

HIV test (18-80 years)

Strategy will pick up to 85% of all immune defects

Question 9

front line ix for immune deficiency: chemistry

Answer 9

renal and liver profile

calcium and bone profile

total protein and albumin

urine protein/Cr ratio

serum

protein electorpohoresis

serum free light chains

Question 10

front line ix for immune deficiency: serum Ig

Answer 10

1. check lab issues age-releted reference intervals especially for children
2. Ig profile helpful in diagnosis

• isolated IgG reduction = protein loosing enteropathy, prednisolone >10mg/day
• reduction IgG and IgM = monitor for B cell neoplasm, hx of exposure to rituximab
• reduction in IgG and IgA = primary antibody deficiency

Question 11

front line ix for immune deficiency: electrophoresis

Answer 11

Question 12

second line test to ix for immune deficiency: vaccinae antibodies

Answer 12

measure concentration of vaccine antibodies

• tetanus toxoid = protein antigen
• pneumovax vaccine = carbohydrate antigen (all 23 serotypes or to individual pneumococcal serotypes)

if vaccine antibody levels low = offer test immunisation with pneumovax II and tetanus to ix immune function

failure to respond to vaccination is part of diagnostic criteria for a nymber of 1o antibody deficiency syndromes and is a criteria for receipt of IgG replacement theerapy for 2o antibdoy defiicency syndromes

Question 13

NOT DONE second line test to ix for immune deficiency:

Question 14

mx of 2o immune deficiency

Answer 14

tx underlying cause

advise on measures to reduce exposure to infection

immunise against resp viruses and bacteria and offer vaccines to household contacts

education to tx bacterial infections promplty: may require high and longer therapies courses

prophylactic abx for confirmed recurrent bacterial infections

Question 15

IgG replacement therapy for 2o antibody deficiency sundromes

Answer 15

Question 16

HIV-1 virology

Answer 16

Question 17

5 characteristic features of the immunology of HIV-1 infection

Answer 17

Question 18

diagnosis of HIV-1 infection

Answer 18

Question 19

baseline ix hiv

Answer 19

Question 20

evaluation and mx of HIV-1 infection

Answer 20

Question 21

cd4+ cell count and opportunistic infections

Answer 21

Question 22

HIV-1 specific tests

Answer 22

Question 23

standard ART in UK

Answer 23

• 2 NRTI and 1 NNRTI or 2NRTI and 1 Integrase inhibitor are standard first line anti-HIV-1 treatments in the UK
• Considerable efforts in last 5-10 years to combine different ART drugs in a single pill formulations to improve adherence to therapy
• Drug toxicity rather than virological failure is the main reason why HIV-1 patients change HIV therapy
• It is safer to continue to take ART rather than interrupt anti-HIV treatment course (SMART study)

Question 24

monitoring individuals on ART

Answer 24

Check for compliance with drug therapy and for adverse side effects

Regular HIV-1 viral load

Monitor liver, renal, bone and lipid toxicity

CD4 T cell monitoring not needed for counts more than 350cells/ul

Assess cardiovascular and osteoporosis risk