Human Immunodeficiency Virus and Acquired Immune Deficiency Syndrome

HIV is a retrovirus that infects immune cells, leading to:

An initial, non-specific viral infection
Termed seroconversion illness.
Chronic immunodeficiency
Termed AIDS.

When it was first identified, HIV was named HTLV-3 (Human T-lymphotropic Virus), and the more common (and pathogenic) variant named HIV-1 after the rarer and less virulent HIV-2 was discovered in West Africa.

Epidemiology and Risk Factors

Pathophysiology

Viral exposure results in:

Initial infection of cell surface receptor
Classically CD4, though other receptors are implicated as co-receptors.
- Viral RNA is integrated into cellular DNA
- RNA transcribed from cellular RNA, and translated into viral protein
Initial viraemia presents as seroconversion illness, and is typically controlled by initial immune response
HIV replication continues in a largely asymptomatic fashion
Progressive immune deficiency occurs despite persistent host immune response, with ↓ in CD4+ T cells
Rate varies depending on host and viral factors:
- Median ~9 years
- Some show no evidence of CD4 loss for up to 15 years

Aetiology

Clinical Manifestations

Seroconversion illness occurs 1-4 weeks following exposure:

Fever
Lymphadenopathy
Headache
Photophobia
Fatigue

Chronic infection may cause:

Fever
Weight loss
Lymphadenopathy
Diarrhoea

Diagnostic Approach and DDx

Investigations

Bedside:

Laboratory:

Bloods
- Diagnosis
  - anti-HIV antibodies
    Diagnostic of infection; positive in most patients within 3 months of infection.
- Monitoring
  3-4 monthly testing in stable patients.
  - HIV viral load
  - CD4+ count
    - Best indicator of severity of immunodeficiency and susceptibility to infection
    - AIDS-related illnesses unlikely if >200

Imaging:

Other:

Management

Resuscitation:

ABC approach. Comment on team coordination and clinical priorities.

Specific therapy:

Pharmacological
- Antiretroviral therapy
  Each drug acts at different points in the replication cycle, and so combination therapy is essential.
  - Triple combination therapy usually leads to sustained control without resistance development
  - Initiation by HIV specialist
  - Potential significant drug interactions
  - Timing of therapy in the setting of infection is controversial
    In general:
    - Delay initiation until 2-4 weeks after treatment of aids defining illness
      Longer in more severe disease with ↑ risk of Immune Reconstitution Inflammatory Syndrome.
Procedural
Physical

Significant drug interactions may occur with:

Anaesthetics
- Midazolam
Antimicrobials
Antiemetics
Anticonvulsants
Anticoagulants
Statins

Supportive care:

Disposition:

Preventative:

Marginal and Ineffective Therapies

Anaesthetic Considerations

Complications

Divided into:

Pulmonary infections are more common at higher CD4 counts, extra-pulmonary infection becomes more common as CD4 counts fall.

Direct complications of immune deficiency
- Infections
  - Immunocompromised
    - PJP
    - Oesophageal candidiasis
      Common presenting disease.
    - Cryptococcal meningitis
      Non-specific and not-particularly-meningitic presentation:
      - Headache
      - Fevers
      - Minimal neck stiffness
        Relies on inflammation of the meninges, which in turn relies on a functioning immune response.
    - Mycobacterium avium complex
    - CMV retinitis
    - TB
    - Cerebral toxoplasmosis
      - Focal encephalitis
      - Requires brain biopsy for diagnosis
  - Generic
    - Sepsis
    - Pneumonia
- Tumours
  - Immunocompromised
    - T-cell lymphoma
      Particularly CNS lymphomas.
    - Karposi Sarcoma
      Angioproliferative tumour of epithelium relating to herpes virus 8 infection, which presents as red-purple lesions on skin and oral and gastric mucosa.
- Immune reconstitution syndrome
Indirect complications
- C
  - Autoimmune vasculitis
  - Dilated cardiomyopathy
  - CAD
- D
  - Autonomic neuropathy
- Drug-related
  - Type B lactic acidosis
  - Pancreatitis
  - AKI
  - Stevens-Johnson syndrome

Prognosis

The natural history of HIV is a general decline in immune function with an ↑ burden of exotic and severe disease:

With access to antiretroviral therapy, mortality approaches that of the general population.

Key Studies

References

Nelson, Ann Marie, Yukari C. Manabe, and Sebastian B. Lucas. “Immune Reconstitution Inflammatory Syndrome (IRIS): What Pathologists Should Know.” Seminars in Diagnostic Pathology, Seminars Issue on HIV-related Disease, 34, no. 4 (July 1, 2017): 340–51. .
Bersten, A. D., & Handy, J. M. (2018). Oh’s Intensive Care Manual. Elsevier Gezondheidszorg.