1.2. HIV & AIDS Flashcards
cART
combination ART
R-tropic
CCR5
- T-cells
- macrophages
- dendritic cells
- microglia
X-tropic
CXCR4
- B cells
- monocytes
- some T-cells
AIDS symptoms
i. weight loss
ii. fever, night sweats
iii. fatigue
iv. recurrent infections
AIDS diagnosis
i. an AIDS-defining illness, or
ii. CD4 count <200 cells/mm
AIDS-defining illness definition
infections/ cancers which are life-threatening to people infected with HIV
Examples of AIDS-defining illnesses
- HSV-1 (Herpes simplex virus 1)
- salmonella (gut)
- Pneumocystis pneumonia
- Kaposi’s sarcoma
- Toxoplasmosis
- Candidiasis (or thrush)
- TUBERCULOSIS
AIDS
Acquired Immuno-Deficiency Syndrome
* symptoms and illnesses that develops at the final stageof HIV infection, if left untreated
•It’s also called advanced or late-stage HIV infection.
•Result of destruction of the immune system (CD4 cells) by infection with HIV.
•May take 10 to 15 years to develop, depending on age, health and background.
•AIDS leads to death.
* Opportunistic infections are the hallmarks of AIDS
opportunistic infections definition
infections & infection-related cancers that occur more frequently or severely in people with weak immune systems
Fiebig Stages of Early HIV Infection:
The classification system used to describe various stages of early HIV infection and based on the timing and results of diagnostic tests.
Human Immuno-deficiency Virus
*is a retrovirus (Retroviridae)
•contains an RNA-based genome •integrates permanently into the host cell’s DNA-based genome
cellular targets for HIV-1 infection
Minor coreceptors:
- GPR1 (CD4Treg)
- CX4CR1 (Macrophage)
- APLNR (Glial)
cellular targets for HIV-1 infection
Co-receptors:
CXCR4 (X-4 tropic)
CCR5 (R5-tropic)
dual tropic
cellular targets for HIV-1 infection
Main receptor:
Cluster of differentiation-4 (CD4
Anatomical Targets for HIV-1 infection
Vaginal and penile mucosa
- Epidermal LHCs capture HIV.
- Migrate to lymph nodes.
- Present HIV to CD4+T cells
- Infection, spread!
- Inflammation/STIs increases the risk of infection
Anatomical Targets for HIV-1 infection
Rectal mucosa
- The rectal lining is very thin and easy to breach
- Lymph glands are near the rectum.
- These glands are rich in cells susceptible to HIV infection.
- The risk of HIV infection 10 to 20 times greater than unprotected vaginal sex!
Anatomical Targets for HIV-1 infection
Lymph nodes
- These are the major reservoir and main site of persistent HIV replication.
- Lymph nodes are major sites of B and T lymphocytes, and other white blood cells.
Gut-Associated Lymphoid Tissue (GALT)
- The gastro-intestinal tract is preferentiallyand profoundlyaffected during acute and chronic HIV infection.
- It is a well-described site of HIV persistence.
Antiretroviral drug resistance:
low genetic barrier to resistance
The virus develops resistance to the drug easily and quickly. Often a single drug resistance mutation is sufficient to cause high level drug resistance
Antiretroviral drug resistance:
high genetic barrier to resistance
The virus develops resistance to the drug slower. Two or more drug resistance mutation are required to cause high-level drug resistance
Tat
protein encoded for by tat gene in HIV-1
- regulatory protein that drastically enhances efficiency of viral transcription
seroconservation
the time period during which a specific antibody develops & becomes detectable in the blood
- after this, antibodies can be detected in blood tests for diseases
window period
time between HIV infection and point where test gives accurate result.
- person can have HIV & be infectious but still test HIV negative
describe the immunological disease progression leading to AIDS
- rapid increase in viraemia in early acute phase which decline to setpoint
- decline in CD4+ T cells coincides with the increase in viral load
- HIV-specific CD8+ cytotoxic T cells responses reduce the viral load & an increase in CD4+ T cells is seen
- HIV-specific binding antibodies appear after the reduction of viraemia, but antibodies are detectable by ELISA only later in acute infection
- during chronic infection, CD4+ T cells declines slowly & viral load remains stable
- Neutralising antibodies begin to appear
- continued HIV replication & immune evasion exhausts the immune system, leading to opportunistic infection & AIDS
clinical disease progression:
stage 1
- develops within 1-2 weeks
- Flu-like symptoms
- HIV multiplies rapidly, spreads, attacks CD4+ cells
- high risk of transmission
clinical disease progression: chronic stage (clinical latency)
- HIV replicates slowly
- usually no HIV-related symptoms
- can still transmit HIV
- advances to AIDS (in 10 years or longer)
clinical disease progression:
AIDS
- final, most severe stage
- opportunistic disease develop (CD4+ count < 200 cells/ml)
- survival rate is low (about 3 years)
Quasi-species
viral populations in an individual not uniform
IRIS
immune reconstitution inflammatory syndrome
microbicides
antiretroviral drugs
glycan shield
sugary coat
shock
induce HIV expression in latently infected cells through LRA (latency reversing agents)
kill
destroy virus-infected cells by employing strategies involving HIV-specific CD8+ T cells
