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PHRM 865 > Exam 5: HIV/AIDS > Flashcards

Exam 5: HIV/AIDS Flashcards

1
Q

As a general rule, combination antiretroviral therapy (ART) consists of what?

A

two to three active agents from at least two classese

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2
Q

HIV target cell

A

gp120 binds to CD4 receptors on T cells, macrophages, and dendritic cells

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3
Q

How does HIV replication in humans?

A

Infected CD4 cells are impaired from normal functions, and used for viral replication

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4
Q

Routes of transmission for HIV

A
  1. Exposure of mucous membranes or damaged tissue to infected body fluids
  2. Blood stream exposure to infected body fluids
  3. Mother to child
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5
Q

Infected body fluids in HIV

A

blood, semen, pre-seminal fluid, rectal fluid, vaginal secretions, breast milk

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6
Q

What is HIV not found in

A

Urine, feces, sweat, tears

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7
Q

most common mucous membrane transmission

A

sexual transmission

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8
Q

Stages of HIV infection

A
  1. Acute retroviral syndrome
  2. Chronic HIV infection (asymptomatic)
  3. AIDS (symptomatic)
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9
Q

When does acute retroviral syndrome occur

A

In 40-90% of persons w/in 2-6 weeks after initial infection with HIV

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10
Q

acute retroviral syndrome symptoms

A

non specific flu like

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11
Q

acute retroviral syndrome viral load

A

Upper limit of detection (>10,000,000 copies/mL)

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12
Q

What happens in chronic HIV infection

A

antibodies developed against HIV reduce (but do not contain) virus in the serum

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13
Q

chronic HIV infection viral load

A

Viral set point reached 3-6 months after initial infection

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14
Q

chronic HIV infection symptoms

A

generally asymptomatic

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15
Q

AIDS viral load

A

Profound immunosuppression with CD4 <200 cells/mm3

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16
Q

1st laboratory marker for HIV

A 
HIV RNA (plasma)
Detectable 10 days after infection
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17
Q

Laboratory marker for days 14-20 post infection

A

HIV-1 p24 antigen

Transiently detectable b/c antibodies begin to bind to p24 antigen and form immune complexes

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18
Q

What laboratory makers detect IgM

A

3rd and 4th gen immunoassay

expressed 10-13 days after HIV RNA is detectable

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19
Q

which generation of immunoassays have viral detection

A

4th gen

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20
Q

Rapid testing for HIV

A

OraQuick: uses oral fluid OTC

If reactive: seek provider for confirmatory testing

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21
Q

Use of CD4 T lymphocyte cell count for HIV surrogate markers

A

Primary marker of immunocompetence to use before initiation of therapy

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22
Q

What are lower levels of CD4 indicative of

A

more compromised immune system

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23
Q

Use of HIV RNA PCR for HIV surrogate markers

A

Used to assess the effectiveness of therapy

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24
Q

Stage 1 HIV CD4 count

A

> 500

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25
Q

Stage 2 HIV CD4 count

A

200-499

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26
Q

Stage 3 HIV CD4 count

A

< 200 or OI diagnosis

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27
Q

Stage 1 HIV CD4 percent

A

> 26

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28
Q

Stage 2 HIV CD4 percent

A

14-25

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29
Q

Stage 3 HIV CD4 percent

A

<14

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30
Q

NRTIs MOA

A

synthetic purine and pyrimidine analogues which results in elongation termination of growing proviral DNA chain

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31
Q

NRTIs AE

A

mitochondrial toxicity and lactic acidosis with or without hepatomegaly and hepatic steatosis

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32
Q

NRTIs precautions and interactions

A

Require dose adjustment in renal insufficiency

Few clinically significant drug interactions

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33
Q

NNRTIs MOA

A

bind to an allosteric site of the reverse transcriptase enzyme reducing functionality

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34
Q

NNRTIs AE

A

Rash

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35
Q

NNRTIs precautions and interactions

A

caution in hepatic impairment
CYP interactions
High-level resistance develops easily and quickly

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36
Q

PIs MOA

A

inhibit the action of the viral protease preventing the assembly, maturation, and release of new virions

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37
Q

PIs AE

A

GI intolerance (N/V and diarrhea), insulin resistance, and lipodystrophy

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38
Q

PIs precautions and interactions

A

Many are not recommended in severe hepatic impairment
Many drug interactions
Greater pill burden

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39
Q

HIV Boosting Drugs

A

Ritonavir and cobicistat

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40
Q

Ritonavir and cobicistat MOA

A

incredibly potent inhibitors of CYP3A4

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41
Q

Ritonavir and cobicistat use

A

used at low concentrations as a PK enhancer to “boost” the concentrations of other ARVs

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42
Q

ritonavir boosting dose

A

100-200mg qd-bid

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43
Q

cobicistat boosting dose

A

150mg daily

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44
Q

INSTIs MOA

A

inhibits HIV integrase, preventing the proviral DNA integration into the host cell genome

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45
Q

INSTIs AE

A

weight gain

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46
Q

Attachement inhibitor MOA

A

bind to gp120 on the surface of HIV, blocking attachment to the CD4 T-cell co receptor

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47
Q

Post-attachment MOA

A

Binds to domain D2 of the CD4 t-cell co-receptor and interrupts the post-attachment steps required for entry of HIV into the host cell

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48
Q

CCR5 antagonist MOA

A

binds to ccr5 on the cd4 cell surface, blocks the binding of gp120, and prevents entry of HIV into the host cell

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49
Q

Fusion inhibitor MOA

A

binds to gp41 and prevents the fusion and entry of HIV into the CD4 cell

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50
Q

Goals of HIV therapy

A
  1. maximally and durably suppress plasma HIV RNA to below the lower level of detection of the assay (AKA undetectable)
  2. Restore and preserve immunologic function
    3 Reduce HIV-associated morbidity and prolong the duration and quality of survival
  3. Prevent transmission
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51
Q

Benefits of HIV therapy

A
  1. Reduces HIV-related morbidity and mortality
  2. Reduces transmission of HIV
  3. Suppresses viremia
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52
Q

Limitations of HIV therapy

A
  1. Not curative
  2. Interruptions in therapy have serious consequences
  3. Must be continued indefinitely (lifelong)
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53
Q

Issues with interruptions in therapy

A
  1. Rebound viremia (risk of resistance)
  2. Worsening of immune function
  3. Increased morbidity and mortality
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54
Q

When to start ART therapy in HIV

A

ART is recommended for all HIV-infected persons, regardless of CD4 count and should be initiated immediately (or ASAP) after diagnosis

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55
Q

What therapy is not recommended for initial therapy in HIV

A

monotherapy and most dual ART drug combinations

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56
Q

Recommended initial therapy in HIV

A

Two NRTIs in combo with a third active ARV from one of three drug classes

  1. INSTI
  2. NNRTI
  3. PI boosted with a PK enhancer
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57
Q

INSTI + 2 NRTIs initial regimens for most people with HIV

A
  1. bictegravir/TAF/emtricitabine
  2. dolutegravir/abacavir/lamivudine
  3. dolutegravir + TAF or TDF + emtricitabine or lamivudine
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58
Q

INSTI + 1 NRTI initial regimens for most people with HIV

A

Dolutegravir/lamivudine

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59
Q

Measuring ART therapy gold standard

A

No gold standard: monitor viral load and patient self-report

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60
Q

Boosted PIs drug interaction principles

A

strong CYP3A4 inhibitors

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61
Q

which PI is not an inhibitor of 3A4

A

tipranavir

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62
Q

NNRTIs drug interaction principles

A

CYP3A4 induces

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63
Q

which NNRTIs are not CYP3A4 inducers

A

Rilpivirine and doravirine- only substrates

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64
Q

INSTIs drug interaction principles

A

UGT1A1 substates and have fewer clinically significant drug interactions

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65
Q

Which two ARTs are substrates of 3A4

A

maraviroc

fostemsavir

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66
Q

which ART is CI w/ PPIs

A

rilpivirine

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67
Q

which ARTs have its level reduced by acid reduceers

A

atazanavir

rilpivirine

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68
Q

which ART should never be given with Al or Mg

A

raltegravir

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69
Q

INSTIs and antacids relationship

A

separate the two by 6 hours

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70
Q

BZDs and ART relationship

A

With PIs and cobicistat, preferred benzos are lorazepam, oxazepam, and temazepam

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71
Q

Corticosteroids and ART relationship

A

With PIs and Cobicistat, beclomethasone is preferred

72
Q

Statins and ART relationship

A

PIs and cobicistat: low doses of atorvastatin, rosuvastatin, pitavastatin or pravastatin are preferred

NNRTIs: dose may need increased

73
Q

Biguanide and ART relationship

A

dolutegravir increases metformin concentration

74
Q

PDE5 inhibitors and ART relationship

A

PIs and Cobicistat: use very low doses q48-72 hours

75
Q

Polyvalent cation supplements and ART relationship

A

Integrase inhibitors: space apart by 6 hours

Dolutegravir or bictegravir: coadministration of Ca/Fe OK if also taken with food

76
Q

Polymorphic mutations in HIV

A

naturally occurring variants in the absence of therapy

77
Q

what are polymorphic mutations not associated with

A

decreased susceptibility to antiretrovirals

78
Q

Major mutations in HIV

A

amino acid substitutions (point mutations) which confer reduced susceptibility to one or more antiretrovirals posing a survival advantage for the virus

79
Q

Minor mutations in HIV

A

accessory mutations which have little to no effect on drug susceptibility, but may increase the replication fitness of a virus with a major mutation

80
Q

Acquired resistance-associated mutations

A
  1. inadequate adherence
  2. inadequate dosing
  3. inadequate drug concentration
81
Q

What is virologic failure

A

inability to achieve or maintain suppression of viral replication to a viral load of <200 copies/mL

82
Q

Preferred pregnancy NRTI backbones (5)

A
  1. Abacavir/lamivudine
  2. TAF/emtricitabine
  3. TAF + lamivudine
  4. TDF/emtricitabine
  5. TDF/lamivudine
83
Q

Preferred third agent for pregnancy in HIV (4)

A
  1. Dolutegravir
  2. Raltegravir (BID)
  3. Ritonavir boosted atazanavir
  4. Ritonavir boosted darunavir (BID)
84
Q

If VL >1,000 copies near delivery

A

schedule c-section at 38 weeks and give IV zidovudine

85
Q

Breastfeeding and HIV

A

breast feeding is not recommended due to risk of transmission, even with viral suppression

86
Q

Undetectable = ?

A

untransmissable

87
Q

Plasma HIV RNA to prevent transmission

A

Maintaining a plasma HIV RNA <200 copies/mL with ART prevents sexual transmission of HIV to sexual partners

88
Q

CIs for PrEP

A
  1. HIV infection
  2. Weight <77 lbs
  3. Poor CrCl
  4. Possible HIV exposure within past 72 hours
89
Q

PrEP Regimens: Oral daily for all risk groups

A

emtricitabine/TDF 200/300mg PO QD

90
Q

PrEP Regimens: Oral daily for men and transgendered women who have sex with men

A

emtricitabine/TAF 200/25mg PO QD

91
Q

PrEP Injection

A

Cabotegravir 600mg IV:

  1. initial first dose
  2. 2nd dose 1 month after 1st dose then
  3. every 2 months therafter
92
Q

PEP regimen

A

emtricitabine/TDF 200/300mg PO QD x28
+
Raltegravir 400mg PO BID x28 or Dolutegravir 50mg PO QD x28

93
Q

When to initiate PEP regimen

A

ASAP

must be initiated within 72 hours or little benefit will be obtained

94
Q

Preferred NRTI therapy options

A
  1. Abacavir
  2. Emtricitabine
  3. Lamivudine
  4. TDF
  5. TAF
  6. Zidovudine
95
Q

abacavir adult dose

A

600mg QD

300 mg BID

96
Q

emtricitabine adult dose

A

200mg qd

240 mg qd oral solution

97
Q

lamivudine adult dose

A

300mg daily

150mg BID

98
Q

TDF adult dose

A

300mg QD

99
Q

TAF adult dose

A

25mg qd

10mg qd if boosted

100
Q

abacavir AE

A 
hypersensitivity reaction (HLAB)
mitochondrial toxicity
lactic acidosis
101
Q

TDF AE

A

renal insufficiency, osteomalacia

102
Q

NNRTIs naming

A

-vir-

103
Q

1st gen NNRTIs

A

efavirenz

nevirapine

104
Q

2nd gen NNRTIs

A

etravirine

rilpivirine

105
Q

3rd gen NNRTIs

A

doravirine

106
Q

efavirenz dosing

A

600mg qd on empty stomach

400mg qd in low dose coforumalation

107
Q

efavirenz AE

A

rash, CNS

108
Q

nevirapine dosing

A

200mg BID (dose titrated over 14 days)

109
Q

etravirine adult dosing

A

200mg BID with food

110
Q

rilpivirine adult dosing

A

25mg qd with meal

111
Q

dravirine adult dosing

A

100mg qd

112
Q

PIs naming

A

-navir

113
Q

PI drugs (11)

A
  1. atazanvir
  2. atazanvir/cobicistat
  3. darunavir
  4. darunavir/cobicistat
  5. Fosamprenavir
  6. indinavir
  7. lopinavir/ritonavir
  8. nelfinavir
  9. ritonavir
  10. saquinavir
  11. tipranavir
114
Q

atazanvir and atazanvir/cobicistat adult dosing

A

400mg with food if only A

300 A + 100 C qd

115
Q

atazanvir and atazanvir/cobicistat AE

A

indirect hyperbilirubinemia

116
Q

darunavir and darunavir/cobicistat adult dosing

A

800 D + 100 R qd

600 D + 100 R BID

117
Q

darunavir and darunavir/cobicistat AE

A

skin rash

118
Q

Fosamprenavir adult dosing

A

700mg BID + 100mg BID R

1400mg BID naive

119
Q

Fosamprenavir AE

A

Skin rash

120
Q

indinavir adult dosing

A

800mg q 8 h

800mg BID + 100-200 R BID

121
Q

lopinavir/ritonavir adult dosing

A

400/100mg BID

122
Q

nelfinavir adult dosing

A

1250mg BID

123
Q

ritonavir adult dosing

A

100-400mg (boosting)

600mg BID

124
Q

ritonavir AE

A

n/v/d

125
Q

saquinavir adult dosing

A

1000mg BID + ritonavir 100mg BID

126
Q

tipranavir adult dosing

A

500mg BID + ritonavir 200mg BID

127
Q

cobicistat adult dosing

A

150mg QD

128
Q

cobicistat AE

A

increased SCr

129
Q

INSTI naming

A

-tegravir

130
Q

First gen INSTI

A

raltegravir

elvitegravir

131
Q

Second gen INSTI

A

dolutegravir

bictegravir

132
Q

raltegravir adult dosing

A

400mg BID

133
Q

raltegravir AE

A

CK elevations, hepatotoxicity, skin rash

134
Q

elvitegravir adult dosing

A

85mg QD with ATV/r, LPV/r

150mg qD with DRV/r, AMP/r, TPV/r

135
Q

elvitegravir AE

A

N/D

136
Q

Dolutegravir adult dosing

A

50mg QD if naive

50mg BID if experienced

137
Q

bictegravir adult dosing

A

50mg qd

138
Q

what drug is an attachment inhibitor

A

fostemsavir

139
Q

fostemsavir dosing

A

600mg BID

140
Q

fostemsavir AE

A

QTc prolongation

141
Q

what drug is a post-attachment inhibitor

A

ibalizumab-uiyk

142
Q

ibalizumab-uiyk adult dosing

A

2000 mg IV once (loading) then 800mg IV q 2 weeks

143
Q

ibalizumab-uiyk AE

A

dizziness

144
Q

what drug is CCR5 antagonist

A

Maraviroc

145
Q

maraviroc adult dosing

A

300mg BID
150mg BID (CYP inhib/indu)
600mg (CYP indu)

146
Q

what drug is fusion inhibitor

A

enfuviritide

147
Q

enfuviritide adult dosing

A

90mg SQ BID

148
Q

biktarvy formulation

A

bictegravir + emtricitabine + TAF

149
Q

dovato formulation

A

dolutegravir + lamivudine

150
Q

triumeq formulation

A

abacavir + dolutegravir + lamivudine

151
Q

cimduo formulation

A

lamivudine + tdf

152
Q

descovy formulation

A

emtricitabine + TAF

153
Q

temixys formulation

A

lamivudine + TDF

154
Q

truvada formulation

A

emtricitabine + TDF

155
Q

ATR backbone options

A
  1. ABC/3TC (with DTG only)
  2. TDF/FTC
  3. TDF/3TC
  4. TAF/FTC
  5. 3TC (wtih DTG only)
156
Q

ART anchor options

A

BIC

DTG

157
Q

If baseline CD4 <200, do not use

A
  1. RPV-based regimens

2. DRV/r plus RAL

158
Q

If HIV RNA >100,000, do not use

A
  1. RPV based regimens
  2. ABC/3TC with EFV or ATV/r
  3. DRV/r plus RAL
159
Q

If HIV RNA >500,00, do not use

A
  1. RPV based regimens
  2. ABC/3TC with EFV or ATV/r
  3. DRV/r plus RAL
  4. DTG/3TC
160
Q

ART options to start before drug resistance results are available

A
  1. BIC/TAF/FTC
  2. DTG + (TAF OR TDG) + (3TC OR FTC)
  3. (DRV/R or DVR/c) + (TAF or TDF) + (3TC or FTC)
161
Q

ART regimens that can be taken without regard to food

A

bic-,dor-,dtg-, or ral-based regimens

162
Q

ART regimens that should be taken with food

A
  1. ATV/r or ATV/c regimens
  2. DRV/r or DRV/c regimens
  3. EVG/c/TDForTAF/FTC
  4. RPV-based regimens
163
Q

ART regimens that should be taken on empty stomach

A

EVF-based regimens

164
Q

Single tablet regimens for initial ART

A
  1. bic/taf/ftc
  2. drv/c/taf/ftc
  3. dtg/3tc
  4. efv/tdf/3tc
  5. evg/c/tdf or taf/ftc
  6. rpv/tdf or taf/ftc
  7. dor/tdf.3tc
  8. dtg/abc/3tc
  9. efv/tdf/ftc
165
Q

bictegravir/taf/emtricitabine simplicity

A

1 pill/day

166
Q

bictegravir/taf/emtricitabine food requirement

A

no

167
Q

bictegravir/taf/emtricitabine drug interactions

A

few

168
Q

bictegravir/taf/emtricitabine barrier to resistance

A

high

169
Q

bictegravir/taf/emtricitabine ok or no with CKD

A

OK

170
Q

bictegravir/taf/emtricitabine ok or ? with CAD

A

OK

171
Q

dolutegravir/abacavir/lamivudine simplicity

A

1 pill/day

172
Q

dolutegravir/abacavir/lamivudine food requirement

A

no

173
Q

dolutegravir/abacavir/lamivudine drug interactions

A

few

174
Q

dolutegravir/abacavir/lamivudine barrier to resistance

A

high

175
Q

dolutegravir/tdf/emtricitabine ok or no with CAD

A

avoid

PHRM 865 (59 decks)

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