Notes
HIV Progression
Start with a layer of mucosal epithelium and the submucosa; specialized dendritic cells and CD4+ T-cells reside within the submucosa.
Primary Infection
- The first step of primary infection is HIV infection of the mucosa.
- In the submucosa, HIV destroys the T cells, and attaches to dendritic cells.
— HIV can destroy T cells via multiple mechanisms, including direct killing and pyroptosis via inflammasome activation.
- Dendritic cells carry the HIV virions to the lymphoid tissues, including the lymph nodes, where they replicate, establishing infection.
- From the lymph nodes, HIV enters general circulation, aka, viremia.
— Additionally, levels of cytokines and chemokines also increase, with both anti- and pro-viral effects. For example, IFN-alpha and IFN-beta inhibit HIV-1 replication, but, TNF and others stimulate HIV-1 replication.
- In response, the host's anti-viral immune system activates:
— HIV-specific cytotoxic CD8+ T cells partially contain infection.
— Anti-HIV antibodies are produced and can be detected in the blood, thus marking period of seroconversion; this occurs approximately two weeks after infection.
— It is thought that the "founder" virus begins to evolve at this point.
Clinical correlation: Many individuals experience acute retroviral syndrome (aka, seroconversion illness), which is characterized by flu-like symptoms of fever, muscle and joint pains, etc.
Viral set point is established at the end of the primary infection phase; it reflects the balance between viral replication and host immune response – and it may predict the rate of HIV progression due to CD4+ T cell destruction. For example, the higher the set viral load, the more likely the disease will progress to AIDS.
Chronic infection
- This period is characterized by continuous viral replication in the lymph nodes and spleen.
- Clinical latency
— Largely asymptomatic with continuous HIV replication outpaces the production of new CD4+ T cells; thus, chronic infection leads to significant T cell loss. - This period can last for several years.
AIDS
- CD4+ T cell depletion and full immune suppression.
- Thus, progression to AIDS results in fatal vulnerability to opportunistic infections, neoplasms, and neurologic diseases.