Immunodeficiency and HIV

Matching the defect to the infections

• Each arm of immunity guards against particular organisms, so the pattern of infection tells you which arm is missing.

• Superficial Candida (mouth, nails, skin) points to Th17 failure; invasive Candida or Aspergillus points to neutrophil failure.

Antibody and T-cell disorders

• Eczema with infections is not always Wiskott–Aldrich: check the platelets (small and low in WAS) and IgE (very high in hyper-IgE).

Phagocyte disorders

• Chronic granulomatous disease (CGD): NADPH oxidase defect, so neutrophils cannot make superoxide (no respiratory burst). Infections with catalase-positive organisms: S. aureus, Aspergillus (a leading cause of death), Serratia, Nocardia, Burkholderia, Klebsiella; granulomas; recurrent lymphadenitis and liver abscesses.
• Why catalase matters: catalase-negative bacteria (streptococci) release their own H₂O₂, which the neutrophil's myeloperoxidase can use to kill them. Catalase-positive organisms destroy their own H₂O₂, so the neutrophil has nothing to work with.
• Test: nitroblue tetrazolium fails to turn blue, or dihydrorhodamine flow test is abnormal. Treat with prophylactic co-trimoxazole and itraconazole, interferon-γ, stem cell transplant.
• Myeloperoxidase deficiency: normal NBT test (respiratory burst intact) but neutrophils lack MPO staining; usually mild; recurrent Candida, especially in diabetics.
• Leucocyte adhesion deficiency (CD18): delayed umbilical cord separation, neutrophilia without pus. Chédiak–Higashi (LYST): giant granules, partial albinism, neuropathy.

Exam trap A normal NBT test excludes CGD; consider MPO deficiency when neutrophils lack the MPO granule enzyme.

Complement disorders and hereditary angioedema

• Terminal complement (C5–C9) deficiency: recurrent meningococcal infection; vaccinate.
• Hereditary angioedema (C1 esterase inhibitor deficiency, autosomal dominant): recurrent non-itchy swelling of face, larynx and gut (colicky pain) without urticaria, often triggered by trauma or dental work. Uncontrolled C1 activation consumes C4 and generates bradykinin.
• Serum C4 is the best screening test between attacks (low); C1 inhibitor level and function confirm.
• Acute attacks: C1 inhibitor concentrate or icatibant (bradykinin B2 antagonist); antihistamines, steroids and adrenaline work poorly. ACE inhibitors worsen it.

Secondary immunodeficiency

• Far commoner than primary: malnutrition (commonest worldwide), HIV, diabetes, kidney and liver disease, malignancy (lymphoma, myeloma, CLL), chemotherapy, steroids, burns, old age.
• Nephrotic syndrome: urinary loss of IgG and factor B (alternative complement pathway) explains pneumococcal peritonitis in children with relapsing nephrotic syndrome.
• Splenectomy: overwhelming infection with encapsulated bacteria (pneumococcus, meningococcus, Haemophilus); vaccinate and give prophylactic penicillin.
• Burns: Candida is the commonest non-bacterial opportunistic organism.

HIV: the virus and its target

• RNA retrovirus (lentivirus), not a DNA virus: reverse transcriptase copies RNA into DNA, integrase inserts it into the host genome.
• Envelope gp120 binds CD4, with co-receptor CCR5 (early) or CXCR4 (later); gp41 mediates fusion. Targets: CD4 T cells, macrophages, dendritic cells, microglia.
• Course: acute seroconversion illness (fever, rash, lymphadenopathy), a long latent period with falling CD4 (HIV has one of the longest incubation periods to clinical disease), then AIDS (CD4 below 200 or an AIDS-defining illness).

HIV testing

• Adults: fourth-generation test (antibody plus p24 antigen) shortens the window period; positives are confirmed with a different assay (Western blot formerly) and viral load by RNA PCR.
• Infants of HIV-positive mothers: maternal IgG crosses the placenta and persists up to 18 months, so antibody tests are useless; confirm with an HIV nucleic acid test (DNA or RNA PCR) at birth, 6 weeks and later.

Opportunistic infections and cancers

• Pneumocystis jirovecii pneumonia is the classic AIDS-defining infection: dry cough, breathlessness, hypoxia on exertion, bilateral perihilar shadowing.
• Oesophageal candidiasis (painful swallowing, white plaques): oral fluconazole empirically; failure to respond needs endoscopy for HSV, CMV or resistant Candida.
• Cryptococcal meningitis may have nearly normal CSF cells and glucose; test CSF cryptococcal antigen or India ink. Cryptosporidium causes chronic watery diarrhoea.
• Cancers: Kaposi sarcoma (HHV-8) is the commonest tumour and skin malignancy in advanced HIV; non-Hodgkin lymphoma (EBV-driven, often extranodal or CNS); invasive cervical cancer (HPV).

HIV treatment and prevention

• Everyone diagnosed starts combination ART regardless of CD4, typically two nucleoside reverse transcriptase inhibitors (tenofovir with lamivudine or emtricitabine) plus dolutegravir.
• Abacavir: test HLA-B*57:01 first; carriers risk a fatal hypersensitivity reaction, and abacavir is never restarted after a suspected reaction.
• Pre-exposure prophylaxis (PrEP): daily tenofovir–emtricitabine for HIV-negative people at ongoing high risk; confirm HIV-negative first, because PrEP in undiagnosed HIV breeds resistance.
• Post-exposure prophylaxis: tenofovir, lamivudine and dolutegravir within 72 hours for 28 days.
• Mother-to-child transmission: maternal ART through pregnancy and breastfeeding (historically zidovudine alone), infant prophylaxis (nevirapine or zidovudine), and infant NAT testing.

Remember Antibodies fight encapsulated bacteria, T cells fight viruses and fungi, neutrophils fight staph and Aspergillus, terminal complement fights Neisseria.

Exam trap Babies of HIV-positive mothers need nucleic acid testing; their antibody test reflects the mother's IgG.

How FCPS asks about this

• Test confirming HIV in a 3-month-old of an HIV-positive mother: HIV nucleic acid test (PCR).
• HIV protein binding CD4: gp120 (co-receptor CCR5).
• CD4 count for PCP prophylaxis: below 200; co-trimoxazole.
• Why CGD spares catalase-negative organisms: they supply their own H₂O₂.
• Eczema, cold abscesses, lung cysts, retained teeth, high IgE: hyper-IgE syndrome, STAT3.
• Recurrent non-itchy swelling without urticaria: hereditary angioedema; screen with serum C4.
• Test before abacavir: HLA-B*57:01; commonest tumour in AIDS is Kaposi sarcoma (HHV-8).