HIV and Secondary Immunodeficiency Flashcards
What are some causes of secondary immune deficiency?
- Malnutrition
- Drugs
- 2nd to infections: Mesales, TB, HIV, potentialls SARS-CoV-2
- ageing, genetic metabolic disease etc. etc.
What are the most common drugs causing immune supression?
- Steroids (Gluco + Mineralcorticoids)
- Cytotoxic agents (MTX, azathioprine, others)
- Calcineurin inhibitors (cyclosporine, tacrolimus)
- Antiepileptic drugs (phenytoin, carbamazepine, levetiracetam)
- DMARD
- Other Biologics and Cellular therapies (e.g. JAK inhibitors: tofacitttinib, other new biologics)
What should be co-prescribed when prescribing rituximab chemotherapy/ other anti-CD20 drugs?
Usually with PCP prophylaxis due to increased risk of fungal infections
How do biological treatments (especially anti-CD20 agents) cause immunodeficiency?
Leading to antibody deficiency –> (increased risk of bacterial/viral/fungal infections)
What lab tests should be done to investigate secondary immunodeficiency?
FISH analysis (recap)
- FBC
- Immunoglobulins (IgG, A M, E)
- Serum complements (C3,4)
- HIV test
–> will pick up cause of 85% of immunodeficiency
What first line chemical blood test should be done in a pateint with 2nd immunodeficiency?
- Renal+Liver profile (incl. urine cr ratio, albumin)
- Calcium and bone
- Serum free light chains + electrophoresis
What does an isolated reduction in IgG suggests?
- Protein loosing enteropathy
- Prednisolone >10mg/day
What does a reduction in IgG and IgM on serum immunoglobulins suggest?
Monitor for B cell neoplasm
? History of exposure of rituximab
What might a reductionin IgG and IgA suggest?
? Primary antibody deficiency
Why would you measure vaccine antibody concentration in investigation for immune deficiency?
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
What are conservative measurements to manage secondary immune deficiency?
- reduce exposure to infection
- immunisation + immunisation of household contacts
What is medical management of secondary immune deficiency?
- Early + longer ABx treatment of bacterial infection
- Prophylactic ABx
- Potentially IgG replacement therapy
What are the criteria for IgG replacement therapy in secondary antibody deficiency syndromes?
What is the difference between HIV 1 and HIV 2?
HIV1 : most common species worldwide
HIV-2: restricted almost completely to West Africa –> slightly less transmission and slower progression
What are the key characteristics oft the HI-virus?
- double-stranded RNA virus
- retrovirus –> integration into host genome
What are the effects of untreated HIV infectionon in the lymph nodes?
Disruption of lympho node architecture + impaired ability to generatet protective T cand Be cell immune response
Explain the natural progression of HIV infections regarding
1. Viral load
2. CD4 counts
3. Immune activation
Usually acute infection followed by chornic phase (~10 years)
10% are rapid progressors (2-3 years)
- Viral Load: Very high in acute infection (2-14 weeks post-transmission), then decreases in latent phase and increases again in AIDS
- CD4 counts: small dip initially, but then recovers and only dips in AIDS/ symptomatic chronic period
How is HIV testes for?
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
What are the main characteristics of an acute HIV infection?
1. Clinically
2. Bloods (RNA;, CD4 and CD8 counts)
- 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)
What baseline investigations should be done in a patient just diagnosed with HIV?
+ HIV Viral load and HIV genotypes (next generation sequencing)
+ T-cell count (CD4 cound and CD4 : CD8 cell ratio)
What diseases are you predisposed to with a CD4 count <500?
Bacterial Skin infections
HSV Zoster
Fungal infections (skin, oral)
What diseases are you predisposed to with a CD4 count <400?
kaposi’s sarcoma
What diseases are you predisposed to with a CD4 count <300?
Hariy Leukoplakia
Tuberculosis
What diseases are you predisposed to with a CD4 count <200?
PCP/PJP
Cryptococcis
Toxoplasmosis
What diseases are you predisposed to with a CD4 count <100?
CMV
Lymphoma (EBV)
Explain the principles and treatment regiment for HIV infection
Initiation of treatment on triple therapy
Triple therapy
* Two NRTI + 3rd drug of a different class, e.g.
* (usually protease inhibitor or NNRTI)
