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ID exam 4 > HIV/AIDS > Flashcards

HIV/AIDS Flashcards

1
Q

target cell

A

The primary target cell of HIV is the CD4 T helper/inducer lymphocyte
HIV expresses receptor proteins (gp120) which preferentially bind to CD4 receptors on T cells, macrophages, and dendritic cells
CD4 cells are key component of cell-mediated immunity, and are responsible for assisting with antibody production and secreting cytokines to protect the host against bacterial and viral infections
Infected CD4 cells are impaired from normal functions, used by HIV for viral replication, and ultimately destroyed by a direct cytolytic effect

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2
Q

transmission

A

exposure of mucous membrane or damaged tissue to infected body fluids - not urine, feces, sweat or tears
blood-stream exposure to infected body fluids
mother to child
NOT spread by casual contct, spitting, sneezing/coughing, sharing food/utensils, insects, closed-mouth kissing, swimming pools

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3
Q

stages of infection

A

acute retroviral syndrome - chronic HIV infection (asymptomatic) - acquired immunodeficiency syndrome (AIDS) (symptomatic)

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4
Q

acute retroviral syndrome

A

seen in 2-6 after initial infection

characterized by non-specific self-limiting flu-like symptoms

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5
Q

chronic HIV infection

A

antibodies developed against HIV reduce virus in the serum
equilibrium (viral “set-point”) is reached 3-6 mo after initial infection
A higher “set-point” is correlated with greater risk for faster disease progression
at baseline, a patient has 800-1500 CD4 cells/mm^3
CD4 decline is fastest in 1st year, then progressive
this phase is generally asymptomatic and lasts 8-10 years w/out therapy

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6
Q

AIDS

A

profound immunosuppression - no longer able to ward off infectious processes
at CD4 less than 500, patients may develop throush, vulvovaginal candidiasis, oral hairy leukopenia, herpes zoster, bacterial penumonia and peripheral neuropathy
at CD4 less than 200, AIDS-defining opportunistic infections (OIs) can occur

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7
Q

who should be screened for HIV

A

patients aged 13-64 in any health care setting, all pregnant women as early as possible during each pregnancy, all patients treated for tuberculosis, all patient attending STD clinics during each visit for a new complaint

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8
Q

testing methods - dynamics of viremia after HIV infection

A

HIV RNA - 10 days after infection
p24 - 14-20 days but only transiently detectable
IgM antibodies - 10-13 days after HIV RNA is detectable
IgG antibodies are able to be picked up by all generations of testing 18-38 days after HIV RNA is detectable

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9
Q

diagnosis

A

either a positive result from a multitest algorithm or a positive virologic test

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10
Q

CD4 T lymphocyte cell count

A

used to assess overall immunocompetence
particularly useful before initiation of antiretroviral therapy
important for knowing if opportunistic infection prophylaxis should be initiated or discontinued
stage 1: over 500 cells, over 26%
stage 2: 200-499 cells, 14-25%
stage 3: (AIDS): under 200 cells, under 14%

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11
Q

HIV RNA

A

viral load
used to assess the effectiveness of therapy
most useful after the initiation of antiretroviral therapy
higher baseline viral loads are predictive of a patient’s rate of disease progression
pretreatment viral loads also play a role in the selection of drug regimens

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12
Q

staging disease

A

0, 1, 2, 3 (AIDS)
based on CD$ count
stage 0: early infection, established if a positive result is found within 180 days of a negative or intermediate result regardless of CD4 count
stage 3 (AIDS): established if an AIDS-defining opportunistic infection is diagnosed, regardless of CD4 count

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13
Q

NRTIs

A

form the backbone of initial antiretroviral therapy in treatment-naive patients

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14
Q

NRTI MOA

A

the HIV virus encodes an RNA-dependent DNA polymerase called reverse transcriptase
RT converts viral RNA into double stranded proviral DNA which is incorporated into the host cell genome
these agents are synthetic analogues of purine and pyrimidine and must undergo intracellular phosphorylation - enzymes responsible are dependent upon the nucleoside mimicked
-adenosine - tenofovir, didanosine
-cytidine - lamivudine and emtrictabine
-thymidine - stavudine and zidovudine
-guanosine - abacavir
most need to be triphosphorylated (except tenofovir which only requires 2 phosphorylations)
phosphorylated NRTIs compete with native nucleotides for incorporation into growing proviral DNA chain but elongation terminates due to lack of 3’-OH group

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15
Q

NRTI AEs

A

class effects: mitochondrial toxicity and lactic acidosis with or without hepatomegaly and hepatic steatosis - host cell DNA polymerases can also be inhibited by these agents
prior to abacavir therapy, patient must be screened for HLA-B*5701 (positive = fatal hypersensitivity)
abacavir may have increased risk of MI
TDF has been associated with new onset or worsening renal impairment and decreases in bone mineral density
TAF is a novel oral prodrug of TVF which is more stable and has increased safety profile in terms of renal impairment and BMD

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16
Q

NRTI precautions and interactions

A 
most NRTIs are renally eliminated; zidovudine and abacavir are cleared hepatically
all NRTIs (except abacavir) require dosage adjustment in renal insufficiency
few clinically significant drug interactions exist
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17
Q

NNRTI MOA

A

bind an allosteric site of the RT inducing a conformational change which results in reduced functionality of the enzyme - noncompetitive with NRTIs

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18
Q

NNRTI AEs

A

class effects: rash (usually mild; SJS has been reported)

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19
Q

NNRTI precautions and interactions

A

eliminated hepatically
many significant drug interactions exist
high-level resistance develops easily and quickly to agents in the class

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20
Q

protease inhibitors MOA

A

competitively inhibit the action of viral protease, the enzyme responsible for cleavage of precursor polypeptides into functional structural and enzymatic viral proteins
prevents the assembly, maturation and release of new infectious virions

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21
Q

PI AEs

A

Class effects: GI intolerance including nausea, vomiting and diarrhea; insulin resistance and lipodystrophy

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22
Q

PI precautions and interactions

A

all except nelfinavir undergo hepatic metabolism via CYP3A4 and are not recommended in severe hepatic impairment
many, many drug interactions
boosting: ritonavir is a potent inhibitor of CYP3A4 with anti-HIV activity seen at doses of 600 mg BID; clinically its used exclusively at low doses to boost the conc of other coadministered PIs - boosted PIs are characterized by a highly favorable resistance profile but greater pill burden

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23
Q

integrase strand transfer inhibitors MOA

A

inhibit the HIV integrase enzyme preventing the proviral DNA integration into the host cell genome

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24
Q

INSTIs AEs

A

generally well tolerated

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25
Q

INSTIs precautions and interactions

A

eliminated mainly via UGT1A1 glucuronidation
subject to cationic chelation
fewer interations with this class but elvitegravir requires boosting in order to be dosed QD resulting in many clinically significant DIs
resistance can develop easily with 1st gen INSTIs (raltegravir and elvitegravir), dolutegravir has a resistance profile similar to PIs

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26
Q

chemokine coreceptor 5 (CCR5) antagonists MOA

A

binds to CCR5 on the CD4 cell surface, blocking the binding of gp120 and preventing entry of HIV into the host cell

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27
Q

CCR5 antagonists precautions and interactions

A

only active against CCR5-tropic strains of HIV
before treatment can be considered, a tropism assay must be performed
CYP3A4 substratem dosing is dependent upon coadministration of inhibitors/inducers

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28
Q

fusion inhibitor MOAs

A

bind to gp41 and prevent the fusion and entry of HIV into the CD4 cell

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29
Q

fusion inhibitor precautions and interactions

A

rarely used - reserved for deep salvage regimens due to route of administration

30
Q

pharmacokinetic enhancer

A

strong 3A4 inhibitor
cobicistat has no anti-HIV activity
designed to boost elvitegravir, atazanavir or darunavir to allow for once daily dosing without inducing PI resistance

31
Q

benefits of HIV therapy

A

reduces HIV-related morbidity and mortality at all stages of HIV infection (start ARV immediately)
reduces transmission of HIV - early initiation decreased HIV transmission to unifected parter, ARTs should be used to suppress maternal viral load
suppression of viremia - prevents drug-resistant mutations, preserves or improves CD4 cell numbers, decreases inflammation and immune activation thought to contribute to higher rates of CV disease, nephropathy, malignancy and neuropathy

32
Q

persistent viremia results in…

A

immune activation and inflammation which predict CV and thromboembolic events, cancer, neurocognitive dysfunction and frailty
continuous is better than episodic
risk reduction of modifiable risk factors of inflammation (smoking, diet, exercise) and management of other chronic conditions is certainly warranted

33
Q

limitations of HIV therapy

A

eradication of HIV infection cannot be achieved
treatment interruptions are associated with rebound viremia, worsening of immune function and increased morbidity and mortality
ART should be continued indefinitely

34
Q

when to start therapy

A

ART is recommended for all HIV-infected persons regardless of CD4
ART can be deferred due to psychosocial or clinical factors but should be initiated ASAP

35
Q

what to start

A

triple-drug regimens
generally, 2 NRTIs and either INSTI*, NNTRI, or bPI
NRTI: abacavir + lamivudine or tenofovir + emtricitabine

36
Q

initial therapy - INSTI based regimen

A

Dolutegravir/abacavir/lamivudine if HLA B*5701 negative
Dolutegravir plus either tenofovir disoproxil fumarate/emtricitabine or tenofovir alafenamide/emtricitabine
Elvitegravir/cobicistat/tenofovir alafenamide/emtricitabine or
elvitegravir/cobicistat/tenofovir disoproxil fumarate/emtricitabine Raltegravir plus either tenofovir disoproxil fumarate/emtricitabine or tenofovir alafenamide/emtricitabine

37
Q

initial therapy - PI based

A

Darunavir + ritonavir plus either tenofovir disoproxil fumarate/emtricitabine or tenofovir alafenamide/emtricitabine

38
Q

baseline CD4 under 200

A

Do not use: RPV-based regimens; DRV/r plus RAL

Higher rate of virologic failure observed in those with low pre-treatment CD4 cell count

39
Q

HIV RNA over 100,00 copies/mL

A

Do not use: RPV-based regimens, ABC/3TC with EFV or ATV/r, DRV/r plus RAL
Higher rates of virologic failure observed in those with high pretreatment HIV RNA

40
Q

HLA-B*5701 positive

A

Do not use ABC-containing regimen

Abacavir hypersensitivity, a potentially fatal reaction, is highly associated with positivity for the HLA-B*5701 allele

41
Q

one pill once daily regimen desired

A 
ART Options Include:
-DTG/ABC/3TC
-EFV/TDF/FTC
-EVG/c/TDF/FTC or EVG/c/TAF/FTC
-RPV/TDF/FTC or RPV/TAF/FTC
Available as fixed-dose combination tablets
42
Q

food effects

A 
Regimens that Can be Taken Without Regard to Food:
-RAL- or DTG-based regimens
Regimens that Should be Taken with Food:
-ATV/r or ATV/c-based regimens
-DRV/r or DRV/c-based regimens
-EVG/c/TDF/FTC or EVG/c/TAF/FTC
-RPV-based regimens
Regimens that	Should be Taken on an Empty Stomach:
-EFV-based regimens
43
Q

chronic kidney diesase (eGFR under 60 mL/min)

A

Avoid TDF. Use ABC or TAF. TAF may be used if eGFR >30 mL/min
Other Options When ABC or TAF Cannot be Used:
-LPV/r plus 3TC; or
-RAL plus DRV/r (if CD4 count >200 cells/mm3, HIV RNA
under 100,000 copies/mL)

44
Q

osteoporosis

A

avoid ADF, use ABC or TAF

45
Q

psychiatric illnesses

A

consider avoiding EFV and RPV based regimens

can exacerbate psych sxs and may be associated w suicide

46
Q

narcotic replacement therapy required

A

if receiving methadone: consider avoiding EFV-based regimen

If EFV is used, an increase in methadone dose may be necessary

47
Q

high cardiac risk

A

consider avoiding ABC and LPV/r-based regimens

48
Q

hyperlipidemia

A

the following drugs have been associated with deleterious effects on lipids:

  • PI/r or PI/c
  • ABC
  • EFV
  • EFV/c
49
Q

HBV infection

A

use TDF or TAF with FTC or 3TC whenever possible

if TDF and TAF are contraindicated: used FTC or 3TC with entecavir and a suppressive ART regimen

50
Q

TB infection

A

TAF is not recommended with any rifamycin-containing regimen
if rifampin is used:
-EFV can be used w/o adjustment
-if RAL use, increase dose to 800 mg BID
-usd DTG at 50 mg BID only in patients without selected INSTI mutations
if using a PI-based regimen, rifabutin should be used in place of rifampin in TB regimen

51
Q

adherance to ART is crucial in achieving goals of HIV therapy

A

poor adherance is largest cause of treatment failure

success evidenced at adherance levels 80-95%

52
Q

measuring adherance

A

viral load
patient self-report
pharmacy refill records

53
Q

predictors of adherance

A

positive predictors: knowledge about meds, motivation, simple QD regimens, comprehensive care settings, strong provider-patient relationship
negative: untreated psych, neuro impairment, substance abuse, unstable housing, patient concerns about SEs and poor adherence to clinic visits

54
Q

causes of acquired RAMs

A 
RAM = resistance associated mutations
inadequate adherence (most common)
inadequate dosing
inadequate drug concentrations
55
Q

genetic barrier to resistance

A

property of a drug class or drug within a class which describes the number of point mutations required for clinical resistance to develop combined with the difficulty of selection of these variants

  • Boosted-PIs have the highest genetic barrier to resistance
  • Dolutegravir appears to also have a high genetic barrier, but has not been on the market as long as the bPIs
  • Examples of agents with a low genetic barrier to resistance include: NNRTIs, lamivudine, emtricitabine, and raltegravir
56
Q

genotype resistance testing

A

maps genetic sequence of the circulating viral strains and reports RAMs
the standard assay maps reverse transcriptase and protease genes
integrade and gp41 genes can be screened w other assays
a new “archive” assay can analyze the HIV polymerase regions of HIV-infected cells, allowing for resistance information to be elucidated even in the setting of a suppressed viral load

57
Q

phenotype resistance testing

A

assess the in vitro ability of a patient’s virus to replicated in the presence of a drug and compares this to a reference strain

58
Q

clinical scenarios in which resistance testing is warranted

A

At entry to care, regardless of whether ART is initiated immediately or deferred
-Standard genotype of RT and PR genes is preferred
-If initially deferred, consider repeating at time of initiation
Virologic failure or suboptimal virologic response
-Genotype is recommended when failing first or second regimens
-Also sequence integrase gene if failing an INSTI-based regimen
-Phenotypes should be considered in patients with extensive treatment history, particularly to PIs

59
Q

virologic failure

A

inability to acheive or maintain suppression of viral replication to a viral load of less than 200 copies/mL
reasons for failure: high pre-treatment viral load or low pre-treatment CD4, comorbidities affecting adherance, presence of RAMs, incomplete adherance to medication and clinic appointments, interruption to ART or intermittent access to ART, AEs, suboptimal PKs, suboptimal virologic potency, food requirements, high pill burden, DIs, precription errors, cost
assess adherence and drug interactions; if failure persists, perform resistance testing
-if none identified, reinforce adherence
-if resistance identified, reinforce adherence and construct a new regimen with AT LEAST TWO, preferably 3, fully active drugs

60
Q

medication intolerance

A

common reasons to switch: improve adherence, enhance tolerability, change food requirements, minimize DIs, pregnancy, cost/formulary issues
approach: review prior treatment, switch when virologically suppressed, switch to a new regimen which meets the desired reason for the switch, monitor closely for 4-8 weeks

61
Q

prepartum considerations

A

prevent perinatal transmission
women considering pregnancy should be on maximally suppressive ARV
if already on stable regimen, continue unless containing didanosine, stavudine or treatment doses of ritonavir
if not on ART, start:
-NRTI backbone: abacavir/lamivudine or TDF/emtricitabine
-3rd agent: ritonavir boosted atazanavir, ritonavir boosted darunavir OR raltegravir

62
Q

intrapartum considerations

A

most transmissions occur during delivery
high viral load = high rate of transmission
if VL over 1000 near delivery: schedule C-section at 38 weeks; IV zidovudine to mother during labor
if VL under 1000, individual delivery choice can be made

63
Q

postpartum considerations

A

ARV prophylaxis recommended for all newborns for 4-6 weeks
-initiate w/in 6-12 hours of delivery
-4 weeks of zidovudune recommended in full-term infants if mother had consistent viral suppression throughout pregnancy
-6 weeks of combo ARV (zidovudine + nevirapine + lamivudine) for all other infants
breastfeeding is not recommended

64
Q

neonatal HIV detection

A

antibody testing at birth is not helpful
nucleic amplification assays (NATs) are used for neonate HIV diganosis
-HIV DNA PCR is preferred: screen at 14-21 days, 1-2 mo and 4-6 mo; 2 positive NATs on separate specimens are diagnostic for HIV infection
-HIV DNA PCR is done to quanititate the virus
perinatal HIV transmission can be excluded if: 2 negative NATs at 14 days and 1 month (presumptive) OR 2 negative NATs at 1 month and 4 months (definitive)

65
Q

pre-exposure prophylaxis (PrEP)

A

used in persons at high risk
not lifelong; only admin while at high risk and reassessed regularly
emtricitabine/ TDF is only FDA approved regimen
risk groups: MSM (not in a monogamous relationship w a neg partner); heterosexual men and women (not in a monog relationship w a neg partner); inj drug use
testing prior to initiation: negative HIV test w/in 7 days, screen for acute HIV sxs, hepB serology, creatinine must be above 60, pregnancy test
prescriptions should not exceed 90 days and patient should be closely monitored
stop immediately if ever HIV infected
adherence is critical

66
Q

post exposure prophylaxis

A

after an incidental exposure to HIV
healthcare after accidental needle stick or mucous membrane exposure
blood transfusion (92.5% chance of acquiring), intercourse, inj drug use, needle stick
emtricitabin/TDF PO QD plus raltegravir 400 MG PO BID OR dolutegravir 50 mg PO QD x 28
-must be initiated w/in 72 hours
test at baseline; if positive: do not initiate PEP

67
Q

acid reducers DIs

A

Separate antacids from INSTIs by 6 hours, but never give raltegravir with Al or Mg. Atazanavir and rilpivirine are reduced by acid reducers; rilpivirine is contraindicated with PPIs

68
Q

benzos DIs

A

with PIs and cobicistat, lorazepam, oxazepam and temazepam are preferred

69
Q

corticosteroid DIs

A

with PIs and cobicistat, beclomethasone is preferred

70
Q

statin DIs

A

with PIs and cobicistat, low doses of atorvastatin, rosuvastatin, pitavastatin or pravastatin are preferred
with NNRTIs, dose may need increased

71
Q

PDE5 inhibitors DIs

A

with PIs and cobicistat, use very low doses q48-72 h

72
Q

polyvalent cation supplement DIs

A

with integrase inhibitors, space apart by 6 hours

coadministration with dolutegravir OK if taken w food

ID exam 4 (9 decks)

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