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
2
Q
HIV target cell
A
gp120 binds to CD4 receptors on T cells, macrophages, and dendritic cells
3
Q
How does HIV replication in humans?
A
Infected CD4 cells are impaired from normal functions, and used for viral replication
4
Q
Routes of transmission for HIV
A
- Exposure of mucous membranes or damaged tissue to infected body fluids
- Blood stream exposure to infected body fluids
- Mother to child
5
Q
Infected body fluids in HIV
A
blood, semen, pre-seminal fluid, rectal fluid, vaginal secretions, breast milk
6
Q
What is HIV not found in
A
Urine, feces, sweat, tears
7
Q
most common mucous membrane transmission
A
sexual transmission
8
Q
Stages of HIV infection
A
- Acute retroviral syndrome
- Chronic HIV infection (asymptomatic)
- AIDS (symptomatic)
9
Q
When does acute retroviral syndrome occur
A
In 40-90% of persons w/in 2-6 weeks after initial infection with HIV
10
Q
acute retroviral syndrome symptoms
A
non specific flu like
11
Q
acute retroviral syndrome viral load
A
Upper limit of detection (>10,000,000 copies/mL)
12
Q
What happens in chronic HIV infection
A
antibodies developed against HIV reduce (but do not contain) virus in the serum
13
Q
chronic HIV infection viral load
A
Viral set point reached 3-6 months after initial infection
14
Q
chronic HIV infection symptoms
A
generally asymptomatic
15
Q
AIDS viral load
A
Profound immunosuppression with CD4 <200 cells/mm3
16
Q
1st laboratory marker for HIV
A
HIV RNA (plasma) Detectable 10 days after infection
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
18
Q
What laboratory makers detect IgM
A
3rd and 4th gen immunoassay
expressed 10-13 days after HIV RNA is detectable
19
Q
which generation of immunoassays have viral detection
A
4th gen
20
Q
Rapid testing for HIV
A
OraQuick: uses oral fluid OTC
If reactive: seek provider for confirmatory testing
21
Q
Use of CD4 T lymphocyte cell count for HIV surrogate markers
A
Primary marker of immunocompetence to use before initiation of therapy
22
Q
What are lower levels of CD4 indicative of
A
more compromised immune system
23
Q
Use of HIV RNA PCR for HIV surrogate markers
A
Used to assess the effectiveness of therapy
24
Q
Stage 1 HIV CD4 count
A
> 500
25
Stage 2 HIV CD4 count
200-499
26
Stage 3 HIV CD4 count
< 200 or OI diagnosis
27
Stage 1 HIV CD4 percent
>26
28
Stage 2 HIV CD4 percent
14-25
29
Stage 3 HIV CD4 percent
<14
30
NRTIs MOA
synthetic purine and pyrimidine analogues which results in elongation termination of growing proviral DNA chain
31
NRTIs AE
mitochondrial toxicity and lactic acidosis with or without hepatomegaly and hepatic steatosis
32
NRTIs precautions and interactions
Require dose adjustment in renal insufficiency
Few clinically significant drug interactions
33
NNRTIs MOA
bind to an allosteric site of the reverse transcriptase enzyme reducing functionality
34
NNRTIs AE
Rash
35
NNRTIs precautions and interactions
caution in hepatic impairment
CYP interactions
High-level resistance develops easily and quickly
36
PIs MOA
inhibit the action of the viral protease preventing the assembly, maturation, and release of new virions
37
PIs AE
GI intolerance (N/V and diarrhea), insulin resistance, and lipodystrophy
38
PIs precautions and interactions
Many are not recommended in severe hepatic impairment
Many drug interactions
Greater pill burden
39
HIV Boosting Drugs
Ritonavir and cobicistat
40
Ritonavir and cobicistat MOA
incredibly potent inhibitors of CYP3A4
41
Ritonavir and cobicistat use
used at low concentrations as a PK enhancer to "boost" the concentrations of other ARVs
42
ritonavir boosting dose
100-200mg qd-bid
43
cobicistat boosting dose
150mg daily
44
INSTIs MOA
inhibits HIV integrase, preventing the proviral DNA integration into the host cell genome
45
INSTIs AE
weight gain
46
Attachement inhibitor MOA
bind to gp120 on the surface of HIV, blocking attachment to the CD4 T-cell co receptor
47
Post-attachment MOA
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
48
CCR5 antagonist MOA
binds to ccr5 on the cd4 cell surface, blocks the binding of gp120, and prevents entry of HIV into the host cell
49
Fusion inhibitor MOA
binds to gp41 and prevents the fusion and entry of HIV into the CD4 cell
50
Goals of HIV therapy
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
4. Prevent transmission
51
Benefits of HIV therapy
1. Reduces HIV-related morbidity and mortality
2. Reduces transmission of HIV
3. Suppresses viremia
52
Limitations of HIV therapy
1. Not curative
2. Interruptions in therapy have serious consequences
3. Must be continued indefinitely (lifelong)
53
Issues with interruptions in therapy
1. Rebound viremia (risk of resistance)
2. Worsening of immune function
3. Increased morbidity and mortality
54
When to start ART therapy in HIV
ART is recommended for all HIV-infected persons, regardless of CD4 count and should be initiated immediately (or ASAP) after diagnosis
55
What therapy is not recommended for initial therapy in HIV
monotherapy and most dual ART drug combinations
56
Recommended initial therapy in HIV
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
57
INSTI + 2 NRTIs initial regimens for most people with HIV
1. bictegravir/TAF/emtricitabine
2. dolutegravir/abacavir/lamivudine
3. dolutegravir + TAF or TDF + emtricitabine or lamivudine
58
INSTI + 1 NRTI initial regimens for most people with HIV
Dolutegravir/lamivudine
59
Measuring ART therapy gold standard
No gold standard: monitor viral load and patient self-report
60
Boosted PIs drug interaction principles
strong CYP3A4 inhibitors
61
which PI is not an inhibitor of 3A4
tipranavir
62
NNRTIs drug interaction principles
CYP3A4 induces
63
which NNRTIs are not CYP3A4 inducers
Rilpivirine and doravirine- only substrates
64
INSTIs drug interaction principles
UGT1A1 substates and have fewer clinically significant drug interactions
65
Which two ARTs are substrates of 3A4
maraviroc
| fostemsavir
66
which ART is CI w/ PPIs
rilpivirine
67
which ARTs have its level reduced by acid reduceers
atazanavir
| rilpivirine
68
which ART should never be given with Al or Mg
raltegravir
69
INSTIs and antacids relationship
separate the two by 6 hours
70
BZDs and ART relationship
With PIs and cobicistat, preferred benzos are lorazepam, oxazepam, and temazepam
71
Corticosteroids and ART relationship
With PIs and Cobicistat, beclomethasone is preferred
72
Statins and ART relationship
PIs and cobicistat: low doses of atorvastatin, rosuvastatin, pitavastatin or pravastatin are preferred
NNRTIs: dose may need increased
73
Biguanide and ART relationship
dolutegravir increases metformin concentration
74
PDE5 inhibitors and ART relationship
PIs and Cobicistat: use very low doses q48-72 hours
75
Polyvalent cation supplements and ART relationship
Integrase inhibitors: space apart by 6 hours
Dolutegravir or bictegravir: coadministration of Ca/Fe OK if also taken with food
76
Polymorphic mutations in HIV
naturally occurring variants in the absence of therapy
77
what are polymorphic mutations not associated with
decreased susceptibility to antiretrovirals
78
Major mutations in HIV
amino acid substitutions (point mutations) which confer reduced susceptibility to one or more antiretrovirals posing a survival advantage for the virus
79
Minor mutations in HIV
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
Acquired resistance-associated mutations
1. inadequate adherence
2. inadequate dosing
3. inadequate drug concentration
81
What is virologic failure
inability to achieve or maintain suppression of viral replication to a viral load of <200 copies/mL
82
Preferred pregnancy NRTI backbones (5)
1. Abacavir/lamivudine
2. TAF/emtricitabine
3. TAF + lamivudine
4. TDF/emtricitabine
5. TDF/lamivudine
83
Preferred third agent for pregnancy in HIV (4)
1. Dolutegravir
2. Raltegravir (BID)
3. Ritonavir boosted atazanavir
4. Ritonavir boosted darunavir (BID)
84
If VL >1,000 copies near delivery
schedule c-section at 38 weeks and give IV zidovudine
85
Breastfeeding and HIV
breast feeding is not recommended due to risk of transmission, even with viral suppression
86
Undetectable = ?
untransmissable
87
Plasma HIV RNA to prevent transmission
Maintaining a plasma HIV RNA <200 copies/mL with ART prevents sexual transmission of HIV to sexual partners
88
CIs for PrEP
1. HIV infection
2. Weight <77 lbs
3. Poor CrCl
4. Possible HIV exposure within past 72 hours
89
PrEP Regimens: Oral daily for all risk groups
emtricitabine/TDF 200/300mg PO QD
90
PrEP Regimens: Oral daily for men and transgendered women who have sex with men
emtricitabine/TAF 200/25mg PO QD
91
PrEP Injection
Cabotegravir 600mg IV:
1. initial first dose
2. 2nd dose 1 month after 1st dose then
3. every 2 months therafter
92
PEP regimen
emtricitabine/TDF 200/300mg PO QD x28
+
Raltegravir 400mg PO BID x28 or Dolutegravir 50mg PO QD x28
93
When to initiate PEP regimen
ASAP
| must be initiated within 72 hours or little benefit will be obtained
94
Preferred NRTI therapy options
1. Abacavir
2. Emtricitabine
3. Lamivudine
4. TDF
5. TAF
6. Zidovudine
95
abacavir adult dose
600mg QD
| 300 mg BID
96
emtricitabine adult dose
200mg qd
| 240 mg qd oral solution
97
lamivudine adult dose
300mg daily
| 150mg BID
98
TDF adult dose
300mg QD
99
TAF adult dose
25mg qd
| 10mg qd if boosted
100
abacavir AE
```
hypersensitivity reaction (HLAB)
mitochondrial toxicity
lactic acidosis
```
101
TDF AE
renal insufficiency, osteomalacia
102
NNRTIs naming
-vir-
103
1st gen NNRTIs
efavirenz
| nevirapine
104
2nd gen NNRTIs
etravirine
| rilpivirine
105
3rd gen NNRTIs
doravirine
106
efavirenz dosing
600mg qd on empty stomach
| 400mg qd in low dose coforumalation
107
efavirenz AE
rash, CNS
108
nevirapine dosing
200mg BID (dose titrated over 14 days)
109
etravirine adult dosing
200mg BID with food
110
rilpivirine adult dosing
25mg qd with meal
111
dravirine adult dosing
100mg qd
112
PIs naming
-navir
113
PI drugs (11)
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
atazanvir and atazanvir/cobicistat adult dosing
400mg with food if only A
| 300 A + 100 C qd
115
atazanvir and atazanvir/cobicistat AE
indirect hyperbilirubinemia
116
darunavir and darunavir/cobicistat adult dosing
800 D + 100 R qd
| 600 D + 100 R BID
117
darunavir and darunavir/cobicistat AE
skin rash
118
Fosamprenavir adult dosing
700mg BID + 100mg BID R
| 1400mg BID naive
119
Fosamprenavir AE
Skin rash
120
indinavir adult dosing
800mg q 8 h
| 800mg BID + 100-200 R BID
121
lopinavir/ritonavir adult dosing
400/100mg BID
122
nelfinavir adult dosing
1250mg BID
123
ritonavir adult dosing
100-400mg (boosting)
| 600mg BID
124
ritonavir AE
n/v/d
125
saquinavir adult dosing
1000mg BID + ritonavir 100mg BID
126
tipranavir adult dosing
500mg BID + ritonavir 200mg BID
127
cobicistat adult dosing
150mg QD
128
cobicistat AE
increased SCr
129
INSTI naming
-tegravir
130
First gen INSTI
raltegravir
| elvitegravir
131
Second gen INSTI
dolutegravir
| bictegravir
132
raltegravir adult dosing
400mg BID
133
raltegravir AE
CK elevations, hepatotoxicity, skin rash
134
elvitegravir adult dosing
85mg QD with ATV/r, LPV/r
| 150mg qD with DRV/r, AMP/r, TPV/r
135
elvitegravir AE
N/D
136
Dolutegravir adult dosing
50mg QD if naive
| 50mg BID if experienced
137
bictegravir adult dosing
50mg qd
138
what drug is an attachment inhibitor
fostemsavir
139
fostemsavir dosing
600mg BID
140
fostemsavir AE
QTc prolongation
141
what drug is a post-attachment inhibitor
ibalizumab-uiyk
142
ibalizumab-uiyk adult dosing
2000 mg IV once (loading) then 800mg IV q 2 weeks
143
ibalizumab-uiyk AE
dizziness
144
what drug is CCR5 antagonist
Maraviroc
145
maraviroc adult dosing
300mg BID
150mg BID (CYP inhib/indu)
600mg (CYP indu)
146
what drug is fusion inhibitor
enfuviritide
147
enfuviritide adult dosing
90mg SQ BID
148
biktarvy formulation
bictegravir + emtricitabine + TAF
149
dovato formulation
dolutegravir + lamivudine
150
triumeq formulation
abacavir + dolutegravir + lamivudine
151
cimduo formulation
lamivudine + tdf
152
descovy formulation
emtricitabine + TAF
153
temixys formulation
lamivudine + TDF
154
truvada formulation
emtricitabine + TDF
155
ATR backbone options
1. ABC/3TC (with DTG only)
2. TDF/FTC
3. TDF/3TC
4. TAF/FTC
5. 3TC (wtih DTG only)
156
ART anchor options
BIC
| DTG
157
If baseline CD4 <200, do not use
1. RPV-based regimens
| 2. DRV/r plus RAL
158
If HIV RNA >100,000, do not use
1. RPV based regimens
2. ABC/3TC with EFV or ATV/r
3. DRV/r plus RAL
159
If HIV RNA >500,00, do not use
1. RPV based regimens
2. ABC/3TC with EFV or ATV/r
3. DRV/r plus RAL
4. DTG/3TC
160
ART options to start before drug resistance results are available
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
ART regimens that can be taken without regard to food
bic-,dor-,dtg-, or ral-based regimens
162
ART regimens that should be taken with food
1. ATV/r or ATV/c regimens
2. DRV/r or DRV/c regimens
3. EVG/c/TDForTAF/FTC
4. RPV-based regimens
163
ART regimens that should be taken on empty stomach
EVF-based regimens
164
Single tablet regimens for initial ART
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
bictegravir/taf/emtricitabine simplicity
1 pill/day
166
bictegravir/taf/emtricitabine food requirement
no
167
bictegravir/taf/emtricitabine drug interactions
few
168
bictegravir/taf/emtricitabine barrier to resistance
high
169
bictegravir/taf/emtricitabine ok or no with CKD
OK
170
bictegravir/taf/emtricitabine ok or ? with CAD
OK
171
dolutegravir/abacavir/lamivudine simplicity
1 pill/day
172
dolutegravir/abacavir/lamivudine food requirement
no
173
dolutegravir/abacavir/lamivudine drug interactions
few
174
dolutegravir/abacavir/lamivudine barrier to resistance
high
175
dolutegravir/tdf/emtricitabine ok or no with CAD
avoid
