HIV/AIDS Lecture #1 Flashcards
What is the pathogenesis of HIV infection?
glycoprotein 120 (gp120) (on surface of HIV virus) binds to CD4 receptors on T cells, macrophages, and dendritic cells
primary target cell of HIV is the CD4 T helper/inducer lymphocyte
infected CD4 cells are impaired from normal functions, and used for viral replication
ultimately destroyed by a cytolytic effect
What is the impact of HIV infection on the human immune system?
the CD4 T helper/inducer lymphocyte is a key component of cell-mediated immunity
responsible for protecting against viruses, intracellular bacteria, and certain cancers –> weakened immune system, body highly susceptible to infections
infected CD4 cells are impaired from normal functions, and used for viral replication
What are the three routes of transmission of HIV?
- exposure of mucous membrane or damaged tissue to infected body fluids
- blood stream exposure to infected body fluids (blood, semen, pre-seminal fluid, rectal fluid, vaginal secretions, breast milk)
- mother-to-child
What is HIV NOT found in?
urine, feces, sweat, or tears
What is mucous membrane transmission?
sexual transmission most common - receptive anal intercourse carries more risk than insertive anal > receptive vaginal > insertive vaginal > penile-oral fallatio
increased risk of transmission: high viral load of infected partner, presence of an STI, tearing/abrasions, menstruation
What is blood stream method of transmission?
from injection drug use
other methods are rare: blood transfusion, receipt of tissue/organ transplant, tattooing with shared needles, occupational exposure
What are the screening recommendations for HIV?
pts aged 13-64 in any healthcare setting (repeat annually in high-risk groups)
all pregnant women as early as possible (consider repeat test in 3rd trimester)
all pts initiating treatment for tuberculosis
all pts attending STD clinics
testing should be opt-out
What are the methods of HIV diagnosis?
viral detection - nucleic acid test (earliest we can test, at 10 days)
viral detection - 4th generation immunoassay (detects biomarker P24 antigen for acute HIV infection)
antibody detection - 3rd generation immunoassay
antibody detection - 2nd generation immunoassay
antibody detection - 1st generation immunoassay
higher generation of test –> shorter seroconversion window
What is used for the diagnosis of HIV?
positive results from multitest algorithm
positive virologic test: viral load, qualitative HIV NAT - A qualitative HIV NAT (Nucleic Acid Test) is a type of test that detects the presence of HIV RNA (genetic material of the virus) in a person’s blood.
HIV-1/2 antigen/antibody immunoassay - negative
negative for HIV-1 and HIV-2 antibodies and P24 Ag
HIV-1/2 antigen/antibody immunoassay - positive
confirm results with separate test
HIV-1 + and HIV-2 -
HIV-1 antibodies detected
HIV-1 - and HIV-2 +
HIV-2 antibodies detected
HIV-1 + and HIV-2 +
HIV antibodies detected
HIV-1 - or indeterminate and HIV-2 - or indeterminate
HIV-1 NAT –> now look for HIV RNA
HIV-1 NAT+: acute HIV-1 infection
HIV-1 NAT-: negative for HIV-1
What is an at-home HIV test?
rapid testing: results available in 1-30 min
seroconversion window is 3mo, can’t tell what’s happened in the most recent 3 mo
ex. oraquick in-home test using oral fluid
What is OTC rapid test counseling?
patient with reactive results: need to get confirmatory testing
non-reactive results: counsel on seroconversion window (3mo); repeat test if risk event occurred within window period; counsel on methods of risk reduction/prevention
What are the 2 surrogate markers used in assessing the progression of a patient’s infection and effectivness of their antiretroviral regimen?
CD4 T lymphocyte cell count
HIV RNA PCR (viral load)
What is the CD4 T lymphocyte cell count?
primary marker of immunocompetence
most useful before initiation of therapy
lower levels indicative of a more compromised immune system
What is the HIV RNA PCR (viral load)?
used to assess the effectiveness of therapy
most useful after initiation of therapy
higher baseline levels are predictive of faster disease progression
What is disease staging?
stage 0: acute HIV infection in previous 6mo
stage 1: CD4 count >/=500
stage 2: CD4 count 200-499
stage 3 (AIDS): CD4 count <200 or OI diagnosis
What is the difference between HIV infection and AIDS?
HIV: A virus that attacks and weakens the immune system, specifically CD4+ T cells.
AIDS: The final and most severe stage of HIV infection; CD4+ T cell count drops below 200 cells/mm³, or the person develops AIDS-defining illnesses
What is the MOA of nucleos(t)ide reverse transcriptase inhibitors?
synthetic purine and pyrimidine analogues which result in elongation termination of growing proviral DNA chain b/c they lack a 3’OH end
What are the adverse effects of nucleos(t)ide reverse transcriptase inhibitors?
mitochondrial toxicity and lactic acidosis!!
with or without hepatomegaly and hepatic steatosis
seen less with tenofovir, emtricitabine, abacavir, lamivudine
What is the MOA of non-nucleos(t)ide reverse transcriptase inhibitors?
bind to an allosteric site of the reverse transcriptase enzyme reducing functionality
What are the adverse reactions of non-nucleos(t)ide reverse transcriptase inhibitors?
rash
What are the precautions and interactions of non-nucleos(t)ide reverse transcriptase inhibitors?
caution in pts with hepatic impairmet
many drug interactions
high level resistance develops quickly and easily to agents in this class (particulary nevirapine and efavirenz)
What is the MOA of protease inhibitors?
inhibit the action of the viral protease preventing the assembly, maturation, and release of new virions
What are the adverse effects of protease inhibitors?
GI intolerance (N/V/D), insulin resistance, and lipodystrophy
What are the precautions/interactions of protease inhibitors?
not recommended in severe hepatic impairment
many drug interactions
What are the boosting agents?
ritonavir and cobicistat: potent inhibitors of CYP3A4 - given to inhibit metabolism of protease inhibitors
used to “boost” the concentrations of other ARVs
What is the MOA of integrase strand transfer inhibitors (INSTIs)?
inhibits HIV integrase, preventing the proviral DNA integration into the host cell genome
What are the adverse effects of integrase strand transfer inhibitors (INSTIs)?
weight gain
What are the precautions and interactions of integrase strand transfer inhibitors (INSTIs)?
fewer drug interactions then NNRTIs and PIs (except elvitegravir which must be boosted)
resistance develops easily to 1st generation INSTIs (raltegravir and elvitegravir), but 2nd gen INSTIs (dolutegravir and bictegravir) have resistance profile on par with boosted PIs
What is the MOA of attachment inhibitors?
fostemsavir is a prodrug of temsavir
temsavir binds to gp120 on surface of HIV, blocking attachment to CD4 T-cell co-receptor
What are the precautions and interactions of attachment inhibitors?
contraindicated with strong CYP3A4 inducers b/c it decreases conc. of temsavir
What is the MOA of post-attachment inhibitors?
binds to domain D2 of CD4 T-cell co-receptor and interrupts the post-attachment steps required for entry of HIV into host cell
What are the precautions and interactions of post-attachment inhibitors?
IV administration after dilution in 250 mL of NS
no drug interactions
What is the MOA of chemokine coreceptor 5 (CCR5) antagonists?
binds to CCR5 on CD4 cell surface, blocks the binding of gp120 and prevents entry of HIV into host cell (entry inhibitor)
What are the precautions and interactions of chemokine coreceptor 5 (CCR5) antagonists?
before treatment, a tropism assay must be performed! - only active against CCR5 tropic strains of HIV
substrate of CYP3A4
What is the MOA of capsid inhibitors?
binds to the interface between capsid protein (p24) subunits
interferes with multiple steps of the viral lifecycle: uptake of proviral DNA, virus assembly and release, capsid core formation
What are the precautions and interactions of capsid inhibitors?
very long half-life
substrate of CYP3A4
only approved in pts with multidrug resistant infection who are failing their antiretroviral regimen
Which antiretroviral class requires dosage adjustment in renal insufficiency?
nucleos(t)ide reverse transcriptase inhibitors (except abacavir)
