Acquired Immunodeficiency Syndrome (AIDS)

Introduction. 

AIDS is a serious infection of the immune system. Its name suggests that it consists of a syndrome of various clinical manifestations brought about not by the virus itself, but by secondary infections and inability of the immune system to combat these. Initial symptoms of HIV infection are mono-like and difficult to diagnose. True symptoms of AIDS take years to develop.

Many secondary infections occur much more frequently in the AIDS population than in healthy individuals. These infections can help to identify undiagnosed cases of AIDS, but are also the predominant cause of mortality in this population. These infections include:

Summary

• Cause: Human Immunodeficiency Virus (HIV)
• Transmission: Direct contact/body fluids/STD
• Symptoms:
  1. Acute Phase: Mono-like symptoms due to immune response (fever, fatigue, headache)
  2. Chronic phase:  Decline in CD4+ cells to <200/ml
  3. AIDS-related complex: fever, malaise, headache, weight loss, Oral candidiasis, HIV antibodies                                                           
  4.  2° infections: Pneumocystic pneumonia, Mycobacterial pneumonia, tuberculosis, , cyclosporal infection, cryptococcal meningitis, histoplasmosis, toxoplasmosis
  5. Widespread viral infections; CMV, HSV, EBV
  6. CNS infection à ataxia, dementia, tumors
  7. Cancer: Kaposi's sarcoma, oral/rectal carcinoma, lymphoma
• Pathogenesis: Infects and kills (via cytopathic effect) CD4+ cells (helper T-cells, monocytes, macrophages, dendritic cells), resulting in deficient/absent cell-mediated immunity.
• Complications: Latent infection in macrophages persist even if viral load is undetectable
• Treatment: HAART
  1. Nucleoside analogue reverse transcriptase inhibitors (AZT, 3TC)
  2. Non-nucleoside-analogue RT inhibitors (nevirapine)
  3. Protease inhibitors (ritonavir)
• Immunity: none
• Vaccine: none

Pathogenesis of HIV - detail

1. Attachment of HIV to CD4+ cell via gp120 protein spike. Spike also binds to a second receptor on macrophages (CCR5) or T-cells (CXCR4). People with genetic deficiency in these receptors are resistant to HIV infection
2. HIV enters cell by envelope fusion with cell membrane
3. Reverse transcriptase converts viral ssRNA to dsDNA; makes ~ 5 errors per genome
4. dsDNA enters nucleus, is spliced into host chromosome with help of integrase
5. Integrated DNA can be transcribed to form virion proteins (gag, gag-pol, env)
6. Gag and gag-pol must be cleaved by protease into viral proteins
7. Viral genome, tRNA and proteins associate at membrane. After protease cleavage, virions bud off from host membrane