HIV Flashcards
how does hiv retorvirus work?
infects all cells containing the T4 antigen, primarily the CD4 helper inducer lympocytes
-attaches to the T4 antigen, replicates, and causes cell fusion or death
what cells serve as a reservoir of viurs and promotes its dissemination to other organs?
macrophages
how is HIV transmitted?
through bodily fluids: risks include sexual contact, parenteral exposure and perinatal exposure
- sex, IDU, vertical transmission
- artifical insemination, organ transplantation
what is the acute HIV syndrome?
-occurs 2-6 weeks post exposure
infrequently identified, cluster of nonspecific findings similar to EBV infxn; need high index of suspicion
- sx hit w/in days of initally acquiring virus
- after this, virus goes into lysogenic cycle, only shedding occasionally for several years
-some pts may develp persistent generalized lymphdenopathy w/o symptomatic HIV dz
what is the average time of infection to presentation of symptoms?
about 10 years
what are systemic manifestations of HIV?
fever, night sweats, weight loss
what is the wasting syndrome?
result of increased metabolic weight and decreased protein synthesis w/ a disproportionate loss of muscle mass
what are common sights that are common for infxn and malignancies in HIV pts?
lungs, URI, lymph, CNS, PNS, mouth, GI tract, eyes and skin
what is AIDs defined by?
a CD4 count below 200 cells or the development of an AIDs indicator
-can be made with or w/o lab evidence of an HIV infextn
what is the current HIV/AIDs classification sx?
stage I: ASX
stage II: minor sx
stage III: moderate sx
stage IV: AIDS
describe an acute phast reaction
- infxn
- cytokines, chemokines, and prostaglandines into circulation
- cytokines reach brain, cause behaviors associated with infxn
- prostaglandins reach brains fever centers, causing fever
- cytokines reach bone marrow, causing increased monocytee/ neutrophil release
IL1 and TNF reach leiver, causing production of opsonins (ike complement) + protease inhibitors (antivirals) and their relaease into the bloodstream
what are dendritic cells?
antigen resenting cells of epithelial tissues
-types of macrophages
what does is the primary immune response?
- the first exposure
- generally takes 10-17 days to occu after exposure
- sx of illness occurs during these days
- antigen-selected B and T cells proliferate and differentiate into effector cells
what is a secondary immune response?
all other exposures after
- 2-7 days
- greater response bc due to memory cells
What is active immunity?
immune response to a vaccine or pahtogen in a indiviudal
-memory cells
passive immunity?
comes from the administration of antibodies NOT made by the host.
- This results in no memory cell production, because it does not stimulate the action of Helper T cells. There is no long-term immunity.
- Passive immunity can also come from mother to fetus or baby, because antibodies pass in the placenta (IgG) and breast milk (IgA).
what type of virus is HIV?
- membrane coating
- two copes o RNA genome
- reverse transcriptase
how does a retrovirus replicate?
- reverse transcripase uses RNA to produce one DNA strand
- reverse transcriptase produces the complementary DNA strand
- viral DNA enter the nucles and integrates into the chromosome becoming a proviurs
- a provirus DNA is used to produce mRNA
- mRNA is translated to produce viral proteins
- viral particls are assembled and leave the host cell
what does the serology of a chronic HIV infection look like?
- viral load in blood stream is low
- anitbodis to various viral antigens are high
- CD4 counts are gradually going down
how is late stage HIV infxn defined?
-HIV kills more and more helper T cells, the immune response is impaired-including the ability to generate antibodies, even to HIV itself
- this decrease in HIV anbx may be the trigger for the virus returning tinot a lytic phase
- virus will eventually emerge and “go lytic” killing most of the remaining helper T cells in a realiatively short peroid of time
How do emerging viruses cause human diseases?
1) mutation= RNA viruses mutate rapidly bc RNA polymerase has no “prrofreader” fxn
2) contact btw species: viruses can spread, particularly when mutated
3) spread from isolated populations
what are HIV diagnostic studes?
- detect antibodies bia ELISA and Western blot
- need two ELISAs followed by a Western to confirm HIV infx
- western blot confirsm the true postive
when do most pts develop antibodies?
within 6 mnths of expuse
who all should be screend for HIV?
- pts at high risk of infx,
- pts in all health care settting
- all prego women
- written consent is no longer recommended by the CDC
-HIV screening for pts aged 13-64 in all health care settings
what are other laboratory finding one may see in hIV?
anemia, leukopenis, thrombocytopenia, polyclonal hyper gammaglobulinemia,
hypercholesterolemaia
cutaneous anergy
what is cutanious anergy?
inability to react to skin test bc of a weakened immune system
what is the predominant type of HIV found in US?
HIV -1
HIV-2 is found in afrtic
when is the HIV window period?
when antibody tests will not show evidence of disease
-avg of 25 days until antibody tests are positive, make take up to 3 mnths
what comes after the actute phase of HIV?
asymptomatic infx
- few mnths to median of 11 years before AIDs
- HIV replication is present during all stages of infx, and progressively depletes CD4 lymphocytes
-fever, weight loss, D, cough, SOB and oral candidiases as dz progresses
what are some opporunistic infxns seen with AIDs?
pneumocystis pna, toxoplasma gonddii encephalitis
disseminated mycobacterium avium complex dz
cryptococcosis, coccidioidomycosis
Karposi
TB,
bacteral pna
Lymphoma
isosporiasis, chronic intestinal > 1 mnth
what are some quick HIV tests?
Orasure: oral fluid, if positive, western blot
oraquck advance (1/2): oral or blood
p24 antigen: good if you think pt is in window period
PCR for viral load: RNA or nucleic acid- 2 wksamplicfication test (NAAT)- can detect after 11 days
what is the best wat to monitor the illness progression?
CD4 count- measure a the tsame time of day by the same laboratory
how often do CD4 counts need to be measured?
- if > 350, every 6 mnths
- or every 3 mnths or with a change in pt status
- risk of dz progressio increasd with a CD4 count of less than 200 or a CD4lymhpocytes percentage of less than 20
what is the viral load?
measure of hte actively replicating virus, which correlaes with dz progressio: changing viral loads also may support tx response
tx of HIV: primary prevention efforts:
safer sex (latex only), harm reduction programs, drug rehab, screen of all blood products, and universal precautions in health care delivery
secondary prevention methosds
antiretrovirals, chemophohylaxis
- screen for dz such as TB
- counsel on ways to maintin health and prevent spread of dz
when should PEP be started?
w/in 72 hours of exposrue
-the chance of contracting HIV from a needelstick inury involving a pt with knonwn HIV is 0.3%
how often should a health care worker that has been stuck be tested?
6 wks, 3 mnths, 6 mnths
what is an option fo PEP?
antiretroviral therapy: decision to begin therapy based on pt
combo therapy w/ drugs from different calsses should be continued for up to 4 weeks
-full course PEP reduces the chance of HIV transmssion up to 70%
what is the goal of HIV tx?
suppression of the viral load; a rising or persistenly high viral load, clinical progression, or continued immunologic detrioration signals tx failure
what is tx based on?
CD4 count, viral load, and overall pt status
HIV -related illness w/ CD4 count < 500
salmonella Cdiff kaposi sarcoma Mycobateriam TB HSV, HZV
HIV-related illness with CD4< 200
candida (esophagus, bronchi, trachea, lungs
HIV encephalopathy
AIDS dementia syndomre
Pneumocystis jiroveci pna
HIV related illness < 100
B-cell lymphoma (nonhodgkin) toxoplasmosis Isospora Microsporidia Histoplasmosis cryptococcosiss coccidioidomcosis cryptosporidia
hIV related illness < 50 P
PML
MAC
CMV
CNS lymphoma
what are some ex of nucleoside reverse transcriptase inhibitors (NRtI)?
Abacavir Emtricitabine lamivudine stavudine zalcitabine didanosine zidovudine
how to NRTIs work?
competitive inhibitors of HIV reverse transcripase:
leads to termination of viral DNA growth
-blocks viral replicaion
what is zidovudine (AZT) used for?
prevention of materna-fetal transmission
what are some common NRTI combo meds?
Truvada: Emtricitabine/tenofovir
Combivir: zidovudine/lamivudine
Trizivir
NRTI Adverse effects?
lactic acidosis
hepatic steatosis
lipodystrophy: liphypertropy, lipoatropy
Abacavir adr?
- hypersentisitivity rx: screen for HLA B 5701
- rash
- MI
tenofovier adr?
renal impairment, decrease in bone mineral density
HA
GI intolerance
emtricitabine adr?
minimal toxicity
hyperpigmentaion
didanosine and zalcitabine and stavudine adr?
pancreatitis, peripheral neruopathy, hepatitis
non-nucleoside reverse transcriptase inhibitors?
nevirapine delavirdine efavirenz etravirine edurant
NNRTI ADR
hepatoxicity
rash (SJS)
edurant adr
mood changes, depression, hepatitis
Integrase inhibitors?
raltegravir
elvitegravir
dolutegravie
cabotegravir
II MOA
The HIV DNA is then carried to the cell’s nucleus (center), where the cell’s DNA is kept. Then, another viral enzyme called integrase hides the proviral DNA into the cell’s DNA. Then, when the cell tries to make new proteins, it can accidentally make new HIVs.
Integration can be blocked byintegrase inhibitors.
raltegravie adr?
Nausea Headache Diarrhea CPK elevation, myopathy, rhabdomyolysis Ras
dolutegravir ADR
HA
insomnia
rash
proteinse inhibitors
not really used as first line anymore
protease inhibitors to konw?
crixivan: indinavir
kaletra: lopinavir/ritonavir
norvir: ritonavir
PI adr?
Hyperlipidemia Lipodystrophy Hepatotoxicity GI intolerance Possibility of increased bleeding riskfor hemophiliacs Drug-drug interactions
kaletra adr:
GI intolerance
Diabetes/insulin resistance
Possible increased risk of MI
PR and QT prolongation
indinavir adr?
Nephrolithiasis
GI intolerance
Diabetes/insulin resistance
Fusion inhibitor?
Enfuvirtide
binds HIV envelope glycoprotein
prevents viral fusion w/ target membrne
Enfuvirtide ADR
Injection-site reactions
Hypersensitivity reaction
Increased risk of bacterial pneumonia
entry inhibitors?
maraviroc
binds CCR5 protein on human cell membrane, blocking HIV from cell entry
maraviroc adr?
hepatitis, rash
what are some ex pof pharmacokinetic boosters?
ritonavir, cobicistat
boost blood levels of other ARV meds: inhibit P450 3A4 enzymers
what are teh 3 As of HIV tx?
appropriate ARV regimen
adherence
activity testing
what to test and when to test it?
baselline: CD4 X 2, HIV RNA
what do you tst rifth before starting ART?
DC4 and HIV RNA
what to test whil on ART?
CD4 Q 3 – 6 months x 2 yrs If CD4 < 300 cells/mcL After 2 yrs of ART Annually if CD4 > 300
HIV RNA 2 – 4 wks after starting ART Q 4 – 8 wks until < 200 copies/ml Every 3 – 4 months in stable patients Virologic failure: > 200 copies/ml
when do you start treatment?
Pregnancy low CD4 counts (< 200 cells/mcl) high viral load (>100K copies/ml) concomitant hepatitis AIDS-related symptoms
what about drug resistance testing?
Before starting ART
Resistance in 10 - 17% of HIV-infected patients
Recommended for all at initiation
Recommended for all pregnant women
Virologic failure
During ART
< 4 weeks after discontinuation of treatme
what must you screen for before using abacavire?
HLAB5701
what must you check before using maraviroc?
whether or no the pts viral strain uses CCR5
what are the 3 main categories of combo tx for HIV?
1 INSTI + 2 NRTIs
1 PK-boosted PI (actully 2 drugs) + 2 NRTIs
1 NNRTI + 2 NRTIs
NRTI pair should include 3TC or FTC
what are 3 first line combos?
trvada
atripla
stribild
what not to prescribe?
NRTI monotherapy PI monotherapy 2 NRTIs alone 2 NNRTIs 3 NRTIs ABC/3TC/ZDV or TDF/3TC/ZDV may be ok
why does treatment fail?
High pretreatment HIV RNA Low pretreatment CD4 counts Comorbidities Substance abuse Psychiatric or neurocognitive issues Drug resistance Poor adherence (this is the biggest) Accessibility (cost, getting to medical care
what can be prescribed for PrEP?
truvada
-same efficacy as PEP
ADr: N
