AIDS: Pathogenesis, Immune System Effects, Therapy, and Transmission

AIDS: Acquired Immunodeficiency Syndrome

Overview

AIDS is a disease caused by the Human Immunodeficiency Virus (HIV), which targets the immune system, specifically T cells, leading to immune deficiency and increased susceptibility to infections and certain cancers.

HIV Structure and Replication

Retrovirus Characteristics

• Retrovirus: A type of virus that contains RNA as its genetic material and uses reverse transcriptase to synthesize DNA from RNA.

• RNA codes for new DNA in the host cell.

Steps of HIV Infection

1. Binding: The virus binds to T cells (specifically CD4+ T lymphocytes).

2. Entry and Reverse Transcription: The virus releases its RNA into the host cell. The enzyme reverse transcriptase converts viral RNA into DNA.

3. Integration: The newly synthesized viral DNA enters the nucleus and integrates into the host cell's DNA.

4. Replication: The viral DNA is transcribed and translated, producing new viral particles. This process destroys the T cell.

Additional info: Reverse transcriptase is unique to retroviruses and is a key target for antiviral drugs.

Pathogenesis and Disease Progression

Asymptomatic (Symptom-Free) Period

• Can last up to 10 years.

• Virus is not latent; it hides in lymph nodes, where millions of viral particles are present.

• Gradually destroys T cells and breaks down lymph nodes.

• In the final phase, lymph nodes dissolve, releasing large numbers of viruses into the bloodstream.

Cells Attacked by HIV

• Primary target: CD4+ T cells (also called T4 cells).

• Other affected cells: Monocytes, macrophages, cells of the nervous system, skin, kidney, and intestine (to a lesser extent).

Cofactors Influencing Disease Progression

• Poor nutrition

• Stress

• Exposure to other diseases

Clinical Course of AIDS

Initial Response

• Moderate decline in T4 cells.

• Flu-like illness and oral thrush (fungal infection).

• Immune system produces antibodies (seroconversion).

• Patients test positive for HIV but may not show symptoms of disease.

Later Stages (2–10 Years)

• Progressive destruction of T cells.

• Weakened immune responses lead to opportunistic infections:

  • Pneumocystis pneumonia (fungal lung infection)

  • Kaposi's sarcoma (purple skin cancers)

• Virus also attacks macrophages and brain cells, leading to neurological complications.

AIDS Therapy

Vaccines

• Development is challenging due to high mutation rates of HIV.

• No suitable animal models for testing.

Reverse Transcriptase Inhibitors

• Examples: AZT, DDI, Delavirdine

• Block synthesis of viral DNA by inhibiting reverse transcriptase.

• Virus can develop resistance to these drugs.

• Side effects include pancreatitis and inflammation of peripheral nerves.

Protease Inhibitors

• Examples: Ritonavir, Indinavir, Nelfinavir, Saquinavir

• Prevent formation of the protein coat around the virus, inhibiting viral maturation.

Triple Therapy (Highly Active Antiretroviral Therapy, HAART)

• Combines two reverse transcriptase inhibitors and one protease inhibitor.

• More effective at suppressing viral replication and delaying disease progression.

Transmission of AIDS

Mode of Transmission	Details
Sharing of syringes	50–75% of IV drug users are infected
Mother to fetus	During birth or across placenta; 25–40% risk
Sexual transmission	Risk per act: 1 in 100 to 1 in 1000

• Estimated 500,000 to 2 million people in the U.S. are infected.

Key Terms

• Opportunistic infection: An infection caused by pathogens that take advantage of a weakened immune system.

• Reverse transcriptase: An enzyme that synthesizes DNA from an RNA template.

• Protease inhibitor: A drug that blocks the action of protease, an enzyme HIV needs to replicate.