HIV/AIDS Flashcards
Epidemiology of Acquired/Secondary Immunodeficiency
*Most Serious Worldwide Acquired/Secondary ID Syndrome:
AIDS (due to HIV infection)
*Most Common Secondary ID in Well-Developed Countries:
Due to *Cancers involving *Bone Marrow, or *Various Forms of Chemotherapy and Immunosuppressive Therapies
-(Treatment to prevent Graft Rejection or Inflammatory diseases with corticosteroids, cyclosporine…)
- Most Common Cause of ID in Third World Developing Countries:
- Protein-Calorie Malnutrition
HIV Epidemics
- Originated in Africa
- Mutates Frequently, *Leading to Drug Resistance or Differences in Clinical Presentation
Most Prevalent HIV: HIV-1
HIV-2 is less common and less virulent and remains mostly confined to *West Africa and *India.
AIDS Epidemiology
- Spreads in Specific Risk Groups
- Infected persons may Appear “Well” and not be aware.
- Complications Take Years to Develop
- Fatal if Untreated.
HIV Structure
Lentivirus with a *Central Core with *double-stranded RNA and 3 Enzymes:
- Reverse Transcriptase (RT),
- Protease,
- Integrase
- -*RT makes DNA copies of Viral Genome *(Proviral DNA),
- -Which are inserted by Integrase into Host cell Genome.
–*Protease cleaves initial *Viral Protein Precursors into definitive Viral proteins.
–Can’t be eliminated without killing infected cells.
*Small Genome.
Capsid: protein coat that surrounds the genome.
–Most abundant *Capsid Protein is *p24, which *Reacts with the Antibody used in the HIV Serological *Diagnostic Tests, the *ELISA.
–*Major Humoral Immune Response to HIV is toward **Glycoproteins in the Envelope.
- -*Considerable Genetic Variability is clustered in regions encoding **Envelope Glycoproteins
- -> poses challenge to develop successful vaccine.
Lipid Envelope that is stolen from the Human Host cell.
Some surface proteins: *gp120 attaches to target cells that express **CD4 and **Chemokine Receptors (CNCR4 on T cells and CCR5 on Macrophages and Dendritic cells).
–gp120 binds to CD4 on T cells; this is why HIV selectively kills CD4+ T cells and not CD8+ T cells.
–Macrophages and Dendritic cells are infected but not killed.
==> Reservoirs of Infection
HIV Life Cycle
1) Infection of Cell
2) Viral DNA production and Integration into Host Genome (Provirus)
3) Expression of Viral Genes
4) Production of Viral Particles
HIV Pathogenesis
1) *HIV is captured by Dendritic Langerhans cells in Epithelia, who present them to CD4+ cells.
2) *Dendritic Cells and CD4+ T cells are transported to Lymph Nodes,
- -Where further infection of more APCs and CD4+ T cells occurs.
CD4+ T cells are Lysed; their Depletion causes Immunodeficency.
*Macrophages and *Dendritic cells are Latently infected and serve as Reservoirs of infection, carrying the virus throughout the body to *infect more CD4+ cells.
–HIV can infect other cell types via CD4 or chemorecptors, chiefly *Glial cells in CNS, leading to AIDS Dementia.
Within the Cell:
1) HIV infects Host cell
2) Reverse Transcriptase makes Proviral DNA
3) Integrase inserts that into Host cell Genome
4) Infected CD4+ T cells, Macrophages, or Dendritic cells activated by *Stimuli that “turn on” Host cell Cytokine genes, also *“turn on” HIV genes.
5) Virus then takes over biosynthesis in the cell to manufacture new virions, using *Protease to pack and release them.
HIV Progression in Body
- Body’s immune response to HIV includes specific *Antibody and *CTLs.
- -**Neither of these *eliminates HIV or controls infection, resulting in continuous viral proliferation.
Viral particles in serum doesn’t peak until about 6 weeks after infection.
- -Possible Acute HIV Syndrome may occur: non-specific, flu-like symptoms of fever, muscle aches
- -Note: ELISA gives false negative prior to this time.
*Average Time from Infection to Symptoms of Immunosuppresion: *8-10 Years.
- Over the years, the *body compensates by *Increasing Production of CD4+ T cells.
- -*Eventually, Depletion of CD4+ T cells exceeds
–At that point, *Symptoms of Immunodeficiency begin.
–*CD4+ Depletion leads to Reduced Cell-Mediated immunity and to *Viral, *Protozoal, *Fungal Infections.
–Eventual failure of Humoral Immunity due to loss of CD4+.
–Loss of Immune surveillance leads to development of *Neoplasms, most often *Lymphomas and *Kaposi Sarcoma.
–Cytokines released from Macrophages and CD4+ cells induces CNS Tissue Damage.
*Long Survivors: May have chemokine receptor polymorphisms, decreasing the rate of Macrophage infection.
HIV Transmission
Typically occurs across *Mucous Membranes of Genital Tract from infected person to another.
- Male-to-Male or Male-to-Female Transmission is *More Efficient than Female-to-Male,
- -Because there are more virions in seminal than vaginal fluid.
*Overall, the process is Fairly Inefficient since there are relatively few virions.
- Sexual Intercourse
- Parenterally: IV Drug Abuse
- Congenitally: In utero at time of Delivery or Postnatally via Breast Milk.
*40-50% Homosexual/Bisexual Men
25-30% Heterosexuals with high risk partners
20-25% IV Drug Abusers
Risk of HIV Transmission
*Vaginal Intercourse: 0.33%
Receptive Anal Intercourse: 0.30%
*HIV-Contaminated Blood: >90%
Perinatal transmission rate: ~0 now, due to prenatal testing and use of HAART in pregnancy.
*Risk increases with Multiple exposures.
- Risk of Occupational Transmission from a Single *Needle Stick from an infected patient is about *1/1000, still *Very Low
- -whereas 1/5 risk for hepatitis B and 1/50 risk for hepatitis C
HIV Infection Diagnosis
- *ELISA (Serological Enzyme-Linked Immunosorbent Assay):
- -Initial diagnosis of HIV infection.
–*Performance of ELISA is regulated by state law. Some states require patient’s consent; others don’t.
- ELISA is Highly *Sensitive (>99%), but not very specific with common False Positives;
- -Positives were confirmed in the past by *Western Blot
- -*CDC implemented new guidelines.
HIV can be identified by PCR
- -More specific than ELISA
- -Cheaper
- *p24 Antigen Test and PCR to Proviral HIV DNA are the Most useful in Neonates
- -who are born to infected mothers and have passively acquired Maternal HIV Antibody, which would *invalidate the ELISA Serological Test.
*PCR is Mandated along with p24 and ELISA for Screening of Donated Blood.
(HIV is difficult to culture.)
HIV Infection Monitoring
*HIV-1 RNA level (Viral Load) is very useful to determine Progression of Disease and Response to Therapy.
–Increasing HIV-1 RNA levels suggests Advancement of Disease and/or Treatment Failure.
- *CD4 count Below 200 cells/microliter:
- -Strongly associated with *Opportunistic Infections
- -Diagnostic of *AIDS
- CD4 count Greater than 500 cells/microliter:
- -Usually seen in *Asymptomatic Patients
- CD4 count Less than 350 cells/microliter:
- -Implies Substantial Immunosuppression
*Viral Load and *CD4 Counts are used to evaluate progression/treatment efficacy.
–Viral Load should be checked
@*Baseline and @ *2-8 Weeks after *ARV Therapy.
–(Should decline at least 1 log value by week 4)
Thereafter, *Viral Load and *CD4 counts should be done Every *3-6 months.
Stable patients with *CD4 Counts *Greater than 500 may not need CD4 counts and Viral Loads more than *Once a Year.
Virologic Suppression
Undetectable Viral Load
Virologic Failure
Inability of Treatment to Achieve or Maintain Viral Load of **Less than 200 copies/mL
Virologic Rebound
Viral Load > 200 copies/mL After Virologic Suppression
Suboptimal Immunologic Responses
Failure to Achieve or Maintain Adequate CD4 Response Despite Virologic Suppression.
–After 1 year of ARV, CD4 counts usually increase about 150 cells/mL and Plateau after 4-6 years.
