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hypothesis development
male- 30, previously healthy
gay, frequent sex, drug use
conditions associated w immune suppression
ebidemiologic observations
disease in newborn babies
disease in heterosexual patients who had surgery
lack of cases in healthcare workers
identifying the etiologic agent: evidence
drastically reduced t-cell count
blood borne and sexually transmitted pathogen
only viruses known to target t-cells were retroviruses
identified by 3 separate labs
1986 renamed human immunodeficiency virus
need for public health
focus on education to curb higher risk behavior and slow transmission
need to unite unnatural partners
established rapid and clear info dissemination mechanisms
1986: US surgeon general sent info report to houses in US
what are some of the characteristics of HIV (retrovirus)
stores genetic info as RNA
need to make DNA using host cells material
spherical particle
external lipid bilayer envelope
internal protein core
what does the core of HIV contain
RNA
reverse transcriptase
integrase
protease
what is the HIV life cycle
1) HIVs envelope glycoprotein binds to CD4 receptor on human CD4 + cells and allows 2nd binding to WBC receptors, CCR5 or CXCR4
2) HIV enters cell; remove/ exposes capsid; single-stranded RNA converted to double stranded DNA using reverse transcriptase
3) DNA moves to nucleus where it integrates in human DNA by integrase viral DNA copied when human DNA copied; viral proteins produced when human proteins produced
4) with help from enzyme protease, viral proteins from new HIV particle leave cell, mature and infect other cells
How does HIV damage immune cells
integrase and protease also activates apoptosis w/ in CD4 and cell
specific HIV protein remain displayed on surface of infected CD4 and T cells
immune system further reacts and produces antibodies to further identify infected CD4 and T cells
activation of inflammatory cascada inside infected cells—> signals apoptosis
what were some important lab discoveries
HIV mutates rapidly; up to 1000x faster than flu
challenge for vaccine
key points in virus life cycle identified
if interrupted, can halt spread of virus
Transmission of HIV
100% preventable if proper precautions in place
requires exchange of body fluids
sexual transmission
HIV is semen, vaginal cervical fluids
direct transmission into blood stream on highest risk; concern of micro tears
blood transmission
blood transfusion with infected blood
needle sharing-illicit drugs, steroids, tattoos, piercings
mother-to- child transmission
during birthing process, breastfeeding
DIagnostic testing for HIV
ELISA test
measures antibodies in blood
western blot-assats for specific viral protein
viral load
How does HIV infection turn into AIDS disease
healthy adults have CD4 count of 850-1000 CD4 cells per cubic meter of blood
after infection, HIV viral load high but antibodies just being produced CD4 count—> unchanged
several months after infection— viral load decreased because virus inside cells; HIV antibodies rising; asymptomatic period—> can last months to years
viral replication continues, CD4 cells destroyed
AIDS: immune system compromised and unable to fight off infections
reverse transcriptase inhibitors
block ability for transcription of virus RNA into a double-stranded DNA
protease inhibitor definition
interfere in vial assembly process so reduce virus load to attack other cells
initially result in aromatic reduction of virus in blood rapidly rebound when stop medication
vaccines of HIV
VIR-1388: tells immune system to produce T cells that can recognize HIV and signal immune response, uses CMV vector
PrEP
can be taken by HIV (-) people at high risk for HIV infection to prevent HIV
combination of 2 medications- sold as truvada
PrEP interferes with HIV ability to reproduce so body can fight off virus
when taken daily
decrease HIV risk from sex by 99%
decrease HIV risk from injecting drug use by 74%
need to take 7-20 days before effective
can be 2,000/month
what are the challenges of PrEP
limited geographical access
lack of medicaid expansion
low rates of health insurance
barriers: poverty, systemic racism, homophobia stigma
cost
how do we end the HIV epidemic
diagnosing
treating
protecting
responding