AIDS and HIV Pathophysiology

• Acquired Immunodeficiency Syndrome (AIDS) is caused by the Human Immunodeficiency Virus (HIV).
• AIDS pathophysiology involves progressive destruction of the immune system, especially CD4+ T cells (helper T cells).

HIV Entry and Initial Infection

• HIV transmits through bodily fluids like blood, semen, vaginal fluids, and breast milk.
• HIV primarily targets CD4+ T cells, macrophages, and dendritic cells.
• These cells express CD4 receptors and chemokine co-receptors (CCR5 or CXCR4).
• HIV binds to the CD4 receptor and a co-receptor on the host cell, enabling viral RNA entry.

Viral Replication

• Viral RNA becomes DNA via reverse transcription, using the viral enzyme reverse transcriptase.
• Viral DNA integrates into the host cell’s genome via the viral enzyme integrase, forming a provirus.
• The host cell produces viral proteins and RNA, which are assembled into new virions.
• New virions bud from the host cell, acquire an envelope, and infect other cells.

Immune System Dysfunction

• HIV infection directly kills CD4+ T cells and causes apoptosis and immune-mediated destruction.
• Persistent viral replication causes chronic immune activation, leading to immune cell exhaustion.
• CD4+ T cell depletion impairs immune regulation, causing a decline in cell-mediated and humoral immunity.

Progression to AIDS

• As the CD4+ T cell count drops below 200 cells/μL, the risk of opportunistic infections and cancers increases.
• The weakened immune system cannot fend off infections from pathogens normally controlled.
• Examples of opportunistic infections include Pneumocystis pneumonia, tuberculosis, and cytomegalovirus
• AIDS is defined by the presence of specific opportunistic infections, cancers, or other conditions.
• Examples of AIDS defining conditions include Kaposi’s sarcoma, lymphoma, wasting syndrome or HIV encephalopathy

Systemic Effects

• Persistent HIV replication and immune activation causes systemic inflammation.
• Systemic inflammation contributes to cardiovascular, liver, and neurocognitive disorders.
• Continuous immune activation and viral replication leads to the exhaustion of immune cells.

End-Stage Disease

• Profound depletion of CD4+ T cells severely compromises the immune system.
• Depletion of CD4+ T cells leads to life-threatening infections and cancers.
• Chronic infection, inflammation, and opportunistic diseases can lead to multiorgan failure.

Summary

• AIDS pathophysiology is characterized by CD4+ T cell destruction, chronic immune activation, and systemic inflammation.
• These factors lead to severe immunodeficiency and susceptibility to opportunistic infections and cancers.
• Without effective antiretroviral therapy (ART), HIV infection typically progresses to AIDS.
• Progression to AIDS results in significant morbidity and mortality.

This lesson covers the pathophysiology of AIDS, which is caused by HIV. It explains how HIV enters cells, replicates, and progressively destroys the immune system, especially CD4+ T cells. The mechanisms of viral entry, reverse transcription, and integration into the host cell genome are discussed.