HIV and AIDS Flashcards
When was AIDS first recognized as a distinct entity❓
1980
AIDS is characterized by ❓
Immunosuppression
Opportunistic infections
Secondary neoplasms
Neurological manifestations
How many people were living with AIDS in 2016❓
36.7 million, 2.1million children
5000 new infections per day
60% know their status
By 2017, 20.9 million had access to antiretroviral drugs
35million have died from the epidemic
How many people were living with AIDS in Nigeria, in 2016❓
3.2 million
Second largest HIV epidemic in the world
2.9% adult prevalence
160,000 AIDS related deaths
31% adults and 21% children on antiretroviral drugs
What is the cause of AIDS
Human immunodeficiency virus, a retrovirus of the lentivirus family
What are the two forms of HIV
- HIV1
- M (major)
- O (outlier)
- N (neither M nor O) - HIV2-less pathogenic and widely seen in West Africa
Describe the structure of HIV
- Cone shaped core
- Surrounded by lipid envelope from host cell
-Virus core contains: •major capsid protein p24 •nucleocapsid protein p7/p9 •two copies of viral genomic RNA •3 enzymes: protease, integrase, reverse transcriptase
What viral antigen is used to diagnose HIV infection❓
The p24 antigen (most abundant)
What glycoproteins are found on the viral envelops❓
gp120
gp41
The HIV 1 RNA genome contains what genes❓
Pol
Gag
Env
Produce precursor proteins that are cleaves by progresses to yield mature proteins
What has been the major problem in developing a single antigen vaccine❓
Antibody response is targeted against the viral envelope not its cure
What are the routes of transmission of the virus❓
- Sexual transmission:
- Accounts for >75%
- thru blood vessels breached by trauma
- infection of CD4+ cells within the mucosa - Parenteral transmission
- IV drug abusers
- Heamophiliacs (clotting factors from multiple donors)
- HIV infected blood or blood products - Mother to infant
- In utero
- Delivery thru infected birth canal
- Breast milk - Needle stick injuries
0.3% risk of seroconversion
Antiretroviral drugs 24-48hrs
What are the targets of HIV infection❓
Cells expressing CD4+ receptors and chemokine receptors CCR4 and CXCR5:
- CD4+ cells
- Monocytes and macrophages in lymph nodes, spleen, liver, brain lungs, bone marrow
- Dendritic cells in lymphoid germinal centers and lymphoepithelial surfaces (vagina, tonsil, rectum)
Discuss the pathogenesis of HIV
- Infection of cells
-CD4+ cells as receptor
-Chemokine receptors as coreceptors (CCR5 for R5 strain and
CXCR4 for X4 strain)
-R5 strains infect cells of monocyte/macrophage lineage (M-tropic)
-X4 strains infect T cells (T-tropic)
-gp120 envelope glycoprotein+CD4 molecules
⬇️
Conformational change
⬇️
Formation of new recognition site on gp120 for CCR5 and CXCR4
⬇️
Virus+Coreceptors
⬇️
Conformational change in pg41
⬇️
Exposure of hydrophobic region (fusion peptide) at the tip of gp41 - Integration of provirus into the host cell genome
-insertion into cell membrane of target cells
⬇️
Fusion of virus with host cell
⬇️
Virus core containing genome enters the cytoplasm of the cell
⬇️
Virus is uncoated by viral protease and it’s RNA released
⬇️
DNA copy of viral RNA is synthesized by reverse transcriptase
⬇️
DNA is integrated into host cells DNA by integrase enzymes (provirus) - Activation of viral replication
-Maybe activated by extrinsic stimulus like infectious microbes
⬇️
Cell turns on transcription of genes
⬇️
Provirus gets activated
4. Production and release of infectious virus: ⬇️ Transcription of RNAs ⬇️ Translation into proteins ⬇️ Core structure migrates to cell surface ⬇️ Acquires lipid envelope ⬇️ Buds off as infectious viral particle and infects other cells
Following initial infection of HIV, there is a massive lymphoreticular infection and consequent loss of CD4+ cells
This is most severe where❓
In the GUT mucosa
List the mechanisms of CD4+ depletion
- Direct cytopathic effect
- Apoptosis of infected cells via activation of caspase 3
- Pyroptosis of bystander non-productively infected cells via activation of caspase 3
- Release of cytokines that perpetuate chronic inflammation
How is T-cell function in HIV infection affected❓
Massive depletion of T cells, esp. memory T cells
Functional abnormalities in T lymphocytes and other APCs
Destruction of lymphoid architecture
How is B-cell function in HIV infection affected❓
gp41 can promote B cell growth and differentiation
HIV infected macrophages produce ⬆️IL-6 which ⬆️proliferation of B-cells
B cell hyperplasia
🚫antibody responses to newly encountered antigen due to lack of Helper T cells which help in B cell activation
Bone marrow plasmacytosis
Hypergammaglobinemia
Formation of immune complexes
Macrophages and microglia cells in the CNS are the predominant cell types in the brain affected by HIV
True or false
True
Neuropsychological changes are often less than might be expected because❓
Infected microglia may produce soluble factors like IL-1, IL-6 and TNF
Discuss the natural history of HIV
- Acute HIV syndrome(3-12weeks):
- high level of plasma viraemia
- seroconversion (formation of HIV antibodies) after 3-6weeks
- marked reduction in CD4+ cells, return to normal levels
- rise in CD8+ cells
- non-specific flu-like symptoms like sore-throat, fever, myalgia, skin rash which resolve in 2-3 weeks - Chronic phase:
- competition btwn HIV and host immune response (clinical latency period)
- clinically asymptomatic
- steady decline in CD4+ cells - AIDS:
- Breakdown of host defense
- ⬆️in plasma virus, ⬆️viral load
- CD4+ T cells ⬇️ below 200/uL
- severe clinical disease
- long lasting fever, fatigue, weight loss and diarrhea
-AIDS defining illnesses emerge
List protozoal/helminthic AIDS defining infections
- Cryptosporidosis/isosporidosis
2. Toxoplasmosis (pneumonia/CNS infection)
List fungal AIDS defining infections
- Candidiasis (esophageal, tracheal, pulmonary)
- Cryptococcosis (CNS infection)
- Pneumocystis (pneumonia)
- Coccidiodomycosis
- Histoplasmosis
List bacterial AIDS defining infections
- Mycobacteriosis
- Norcadiosis
- Salmonella infections
List viral AIDS defining infections
- CMV
- Herpes Simplex virus
- Varicella zoster
- JC virus
List AIDS defining neoplasms
- Kaposi sacroma
- Non Hodgkins sacroma
- Burkitts lymphoma
- Anal cancer in men
- Primary lymphoma of the brain
- Large immunoblastic lymphoma
- Invasive cancer of the uterine cervix
Treatment❓
Antiretroviral drugs
