HIV & Anti-Retroviral therapy Flashcards
What is UNAIDS 90-90-90?
A global target set for countries to have:
(1) ≥90% HIV+ to be diagnosed
(2) ≥90% HIV+ to be on ART
(3) ≥90% HIV+ to have viral load depressed
What is the cause of HIV and the pathogenesis?
Lentivirus - a type of retrovirus, infecting the immune cells:
(1) CD4+ T helper cells
(2) Macrophages
(3) Dendritic cells
What type of virus is lentivirus?
- Group IV
- ssRNA
- Positive sense
- Enveloped
What is the difference between HIV-1 and HIV-2
(1) HIV-1
(2) HIV-2 - less virulent and less infective
How does the infection of immune cells by lentivirus lead to low levels of helper T cells?
(1) Direct viral killing of infected cells
(2) Increased apoptosis of infected cells
(3) Killing of infected CD4+ T cells by CD8 cytotoxic lymphocytes
What does a CD8 cytotoxic lymphocyte do?
Kills infected CD4+ (Helper) T cells
What effect does increased death of CD4+ (Helper) T cells have?
(1) Increased susceptibility to opportunistic infections
(2) Susceptibility increases as CD4+ (Helper) T cell count falls below critical level
What are the stages of the HIV life cycle?
Lentivirus binds to CD4 receptor to fuse with host cell membrane
Virus uncoats and viral RNA + proteins enter host cell
Viral DNA is transcribed via reverse transcriptase
Viral DNA enters nucleus
Integrates into host genome using viral integrase
New viral DNA is used as genomic RNA
This is used to make new viral proteins
How can HIV enter the body?
Into the bloodstream
or
mucus membranes (vaginal/penis/anus)
Where is HIV present in the body once contracted?
semen
vaginal fluids
breast milk
blood
rectal excretions
How can HIV be transmitted?
Unprotected sex
mother to baby
IV drug use - needle sharing/needle stick injury
blood transfusions
How can HIV spread be prevented?
HIV testing
condoms
post exposure phrophylaxis PEP
pre-exposure phrophylaxis PrEP
Needle exchange programmes & clean needles
blood screening
How is HIV diagnosed
ELISA-immunoassay
detection of antibodies for HIV
detection of p24 antigen
What is the period for which HIV+ patients may test negative with older tests?
3 months
Where can tests be accessed by the public
sexual health clinics
hospitals
GP surgeries
community pharmacies
What tests are undertaken by the patient following an HIV positive diagnosis?
-Immunoassay (ELISA) to differentiate between HIV-1 and HIV-2
-HIV NAT (nucleic acid test)
When do AIDS symptoms occur following HIV infection?
7.5 years post infection
How does HIV lead to death if left untreated?
Progressively destroys all CD4+ (helper) T cell lymphocytes
what is seroconversion?
the acute infection stage of HIV infection, flu-like symptoms: fever, headache, rash
What is clinical latency?
chronic infection (asymptomatic) stage of HIV infection
When does the body’s CD4+ (helper) T lymphocyte count begin to decline in an HIV infection?
Seroconversion, acute infection stage
Are HIV antibodies present in seroconversion?
No, they are only starting to be made
When can common infections be seen in an HIV infection?
chronic latency stage
What characterises AIDS
Immune system can no longer fight infection
Low CD4+ (helper) lymphocyte count
High viral load
When are opportunistic infections observed in HIV infections?
AIDS stage of infection
What happens if an HIV infection (AIDS) is left untreated?
DEATH
How does AIDS develop?
Untreated HIV infection
What is ART and its aims?
antiretroviral therapy
Increase CD4+(helper) T lymphocyte count
Increase quality of life + life expectancy
decrease risk of infections
decrease transmission
decrease viral load
decrease risk progression
What are the types of ART?
Entry/fusion inhibitors
these drugs block HIV from getting inside healthy cells.
RT inhibitors
bind to a specific protein so the HIV virus can’t make copies of itself.
integrase inhibitors
These stop HIV from making copies of itself by blocking a key protein that allows the virus to put its DNA into the healthy cell’s DNA.
protease inhibitors
These drugs block a protein that infected cells need to put together new HIV virus particles.
What stage of the HIV-life cycle does an entry/fusion inhibitor affect?
Stage 1: virus receptor binding
stage 2: virus uncoating and entry of RNA and proteins into CD4+ (helper) lymphocyte t cell
What stage of the HIV-life cycle does an RT inhibitor affect
Stage 3: viral DNA transcription using reverse transcriptase
What stage of the HIV-life cycle does an integrase inhibitor affect?
stage 4: prevents integration of viral DNA into host genome
Which stage of the HIV life cycle does a protease inhibitor affect?
stage 5
prevents generation of new viral proteins
stage 6
prevents assembly of viral proteins and RNA at the CD4+ (helper) T lymphocyte cell membrane
What are the two types of RT inhibitor?
NRTIs
causes DNA chain termination, analogue of dNTPs
NNRTIs
direct inhibitor of HIV reverse transcriptase
How can the formation of mature viral particles be prevented?
protease inhibitor drugs
What is the first line treatment for HIV
combination therapy
2 NRTIs
1 NNRTI/PI/INI
How can viral load be decreased in HIV infections in pregnancy?
Integrase inhibitor drug
How is transmission of an HIV infection from mother to child prevented?
Antenatal screening
Who is PrEP medicine intended for?
HIV negative individuals who are at risk of HIV infection, currently only TRUVADA available
How much as a % does PrEP treatment reduce HIV infection by?
> 90%
