AIDS pathology

HIV Basics - The Immune Hijacker

• Virus: Retrovirus (Lentivirus) targeting immune cells.
• Primary Target: CD4+ T-helper lymphocytes. Macrophages and dendritic cells act as reservoirs.
• Key Glycoproteins:
  • • gp120: Binds to the CD4 receptor.
  • • gp41: Facilitates viral fusion and entry.
• Coreceptors: Requires CCR5 (macrophage-tropic) or CXCR4 (T-cell-tropic) for entry.
• Replication: Uses reverse transcriptase to convert viral RNA into DNA, which integrates into the host genome.

⭐ HIV establishes a latent reservoir by integrating its proviral DNA into the genome of long-lived memory T-cells, making it a lifelong, incurable infection.

Pathogenesis - Immune System Takedown

• Primary Target: CD4+ T-helper lymphocytes, macrophages, and dendritic cells.
• Mechanism: Viral gp120 protein binds to the CD4 receptor and a coreceptor.
  • Early Stage: CCR5 coreceptor (R5-tropic virus).
  • Late Stage: CXCR4 coreceptor (X4-tropic virus).
• Consequence: Progressive depletion of CD4+ T-cells through viral replication, budding (lysis), and apoptosis.
• Immune Collapse: Leads to a critical drop in cell-mediated immunity, defined by a CD4+ count < 200 cells/mm³.

⭐ The CD4:CD8 ratio, normally ~2:1, inverts to <1:1 in AIDS, a key diagnostic indicator of immune dysregulation.

Diagnosis & Staging - Finding the Foe

• Screening: Sensitive ELISA detects anti-HIV (p24) antibodies & antigen.
• Confirmation: Specific Western blot (WB) or HIV-1/2 differentiation immunoassay.
• Viral Load: RT-PCR measures HIV RNA; used for monitoring treatment response and in acute infection.

• Staging (CDC): Based on CD4+ T-cell count.
  • Stage 1: > 500 cells/mm³
  • Stage 2: 200-499 cells/mm³
  • Stage 3 (AIDS): < 200 cells/mm³ or AIDS-defining illness.

⭐ Window Period: Time after infection when serology is negative as antibodies are not yet produced, but viral load (NAAT/PCR) is high and the patient is highly infectious.

Opportunistic Illnesses - When Defenses Fail

As CD4+ T-cell counts decline, the body becomes susceptible to a range of infections and malignancies. The specific opportunistic illness (OI) often correlates with the degree of immunosuppression.

• General OIs: Candida albicans (oral thrush), EBV (oral hairy leukoplakia), HHV-8 (Kaposi sarcoma), Streptococcus pneumoniae (pneumonia).

• Prophylaxis is key:

  • CD4 < 200: Pneumocystis jirovecii pneumonia (PJP). Prophylaxis with TMP-SMX.
  • CD4 < 100: Toxoplasma gondii, Cryptococcus neoformans.
  • CD4 < 50: Mycobacterium avium complex (MAC). Prophylaxis with Azithromycin.

⭐ In an HIV+ patient with headache and fever, the most common cause of meningitis is Cryptococcus neoformans. Diagnosis is made via India ink stain or cryptococcal antigen test on CSF.

• HIV is a retrovirus that depletes CD4+ T-helper cells, causing profound immunosuppression.
• A CD4+ count < 200 cells/mm³ or an AIDS-defining illness confirms the diagnosis.
• High risk for opportunistic infections like Pneumocystis jirovecii pneumonia (PJP), CMV, and Toxoplasmosis.
• Associated malignancies include Kaposi's sarcoma (HHV-8) and EBV-related B-cell lymphomas.
• Neurologic complications like AIDS dementia complex and PML are common in advanced disease.