AIDS - etiology, pathogenesis, organ site damage, pathomorphological features. Complications.
Acquired immunodeficiency syndrome (AIDS) is a retroviral disease caused by the human immunodeficiency virus (HIV). We see depletion of CD4+ T-lymphocytes and profound immunosuppression. Sexual transmission is the most common method of transmission, viruses are present in semen (cellulary and extracellularly), and enters the body through mucosal abrasions, HIV is also present in vaginal and cervical cells of women so can be spread females to males (although 8x less likely). Transmission can also be via IV drug abusers, transmission of infected blood and mother to infant transmission.
HIV is a lentivirus and has two genetic variants (HIV 1 and HIV 2, 1 being the most common).
The main target for the virus is the immune system and CNS. Here is the lifecycle of the virus:
- HIV binds to CD4 and a coreceptor (CCR5 or CXCR4) on T-cells or macrophages causing conformational change allowing HIV to enter the cell
- Once internalised, the viral genome undergoes reverse transcription, in active T-lymphocytes this becomes
- integrated into the host genome where it can remain latent for years
- Once it becomes translated, there is extensive viral replication and CD4+ cell lysis, causing destruction of lymphoid tissue and depletion of CD4+ T-cells
Pathogenesis and progression of HIV
- Begins with acute infection, partly controlled by immune system
- Following this we have acute viremia through the body
- Advances to chronic progressive infection in peripheral lymphoid tissue with progressive cell lysis
- HIV is highly toxic to CD4+ lymphocytes causing massive destruction (drastically alters CD4+:CD8+ ratio)
- HIV also targets macrophages, although does not cause lysis, instead remains inside cell for long periods
The clinical course has three stages:
- Acute primary phase (initial immune response)
- Chronic phase with relative containment of the virus
- Final crisis phase with catastrophic loss of defences
Clinical presentation is wide and varied, includes increase in opportunistic infections (those that do not usually affect people unless immunocompromised), recurrent infections, increased risk of cancers, and many others. There are a few things that are worth noting:
Remember: AIDS = HIV with CD4 below 200 cells/µL or an AIDS-defining illness. Opportunistic infections follow the CD4 count:
- Below 200: Pneumocystis pneumonia
- Below 100: cerebral toxoplasmosis, cryptococcal meningitis
- Below 50: CMV retinitis, Mycobacterium avium complex
- Kaposi sarcoma is a vascular tumour, rare in normal patients, but common in HIV suffers (caused by herpes virus called Kaposi sarcoma herpesvirus)
- B cell non-Hodgkin lymphomas are a second common AIDS-associated tumour