How HIV Attacks the Immune System: Understanding AIDS and Immunodeficiency

HIV (Human Immunodeficiency Virus) causes AIDS by systematically dismantling cell-mediated immunity.

Stepwise Pathogenesis

1. Entry & Targeting: HIV gp120 binds CD4 + CCR5/CXCR4 on CD4+ T-helper cells, macrophages, dendritic cells.
2. Replication & Destruction: Reverse transcription → integration → viral production → cell lysis (cytopathic effect) and immune activation-induced death.
3. CD4+ T-Cell Depletion: Progressive loss of central memory and effector T-cells → impaired orchestration of humoral & cellular immunity.
4. Lymphoid Tissue Fibrosis: Chronic inflammation → collagen deposition in lymph nodes → disrupted architecture → impaired naive T-cell priming and homeostatic proliferation.
5. Immune Exhaustion: Persistent antigen → PD-1 upregulation → T-cell dysfunction.
6. B-Cell Dysregulation: Hypergammaglobulinemia but poor specific antibody responses; loss of memory B-cells.
7. Innate Immune Impairment: NK cell dysfunction, macrophage defects, dendritic cell impairment.

Consequences

• Opportunistic Infections (OIs): Pneumocystis pneumonia, toxoplasmosis, cryptococcal meningitis, MAC, CMV, TB, severe HSV/VZV.
• Malignancies: Kaposi sarcoma (HHV-8), NHL (EBV), cervical/anal cancer (HPV).
• Neurologic: HIV-associated neurocognitive disorder (HAND), vacuolar myelopathy.
• Wasting, Enteropathy, Renal, Cardiovascular Disease.

Treatment Impact

ART suppresses viral replication → CD4 recovery, immune reconstitution, OI prevention, near-normal lifespan. Undetectable = Untransmittable (U=U).