HIV treatment Flashcards
(258 cards)
1
Q
What is the primary aim of treatment of HIV?
A
PREVENT
- mortality
&
- morbidity
2
Q
What are the secondary aims of treatment of HIV?
A
improve LIFE EXPECTANCY
Reduction of sexual TRANSMISSION
3
Q
What is the life expectancy of men and women on ART for HIV?
A
SAME as general population
VL <40 and CD4 >350
4
Q
What is are the negative impacts of depression on HIV care?
A
associated with:
poor ADHERENCE
MORTALITY
5
Q
What is a useful QUICK screening tool for depression?
A
Arroll test
6
Q
What are the TWO questions in the Arrow depression screening tool?
A
During the past month:
- have you often been bothered by feeling down, depressed, or hopeless?
- have you often been bothered by little interest or pleasure in doing things?
7
Q
What factors did the ASTRA study show were associated with higher risk of virological rebound in people on ART?
A
- FINANCIAL hardship
- NON-EMPLOYMENT
- NON-HOMEOWNERSHIP
- NON-university EDUCATION
- lack of SUPPORT network
8
Q
START trial - What was the relative risk reduction of immediate ART start vs deferred ART on morbidity and mortality?
A
57%
9
Q
START trial - What was the absolute risk reduction of immediate ART start vs deferred ART on morbidity and mortality?
A
4.1% vs 1.5%
10
Q
What study results guide initiation of ART in context of AIDS defining infection?
A
ACTG 5164
11
Q
What study results guide initiation of ART in context of asymptomatic chronic HIV infection infection?
A
START
12
Q
At what point should ART be started in a person with an AIDS defining infection?
A
Within 14 days of starting targeting antimicrobial therapy
13
Q
What is the limitation of the ACTG 5164 study in applying it to all people with AIDS infection + starting ART?
A
All patients:
- ORAL medications
- able to CONSENT
May not be generalisable to severely unwell or requiring ICU
14
Q
How might ART timing differ if a person has an infection of the CNS?
A
SEVERE IRIS
possible increased MORTALITY with early ART
Consider delay in ART start
15
Q
What factors increase rate of progression if present in primary HIV infection?
A
LOW nadir CD4 (<350)
HIGH viral load (> 100 000)
diagnosis within 12 weeks of a negative
16
Q
Why should ART not be interrupted?
A
Increased all-cause MORTALITY (SMART study)
17
Q
What are the BENEFITS of starting ART immediately for PHI?
A
- IMMUNE recovery to normal levels
- Patient taking CONTROL of illness
- reduced TRANSMISSION
- reduced overall MORBIDITY
- reduce viral RESERVOIR
- improve SYMPTOMS
18
Q
Within what time frame from PHI is a CD4 less likely to return to normal when ART started?
A
over 12 months from PHI
19
Q
How quickly is virological suppression achieved after ART initiation?
A
3-6 months
INSTIs 1-3 months
20
Q
What is the recommended drug classes for a PLWHIV who is ART naive?
A
TWO nucleoside reverse transcriptase inhibitors (NRTIs)
+
RITONAVIR boosted PI
or
Non-nucleoside reverse transcriptase inhibitor (NNRTI)
or
Integrase inhibitor
21
Q
What is the preferred NRTI back bone for ART?
A
Tenofovir disoproxil (or alafenamide)
+
emtricitibine
22
Q
What is the alternative NRTI back bone for ART?
A
abacavir
+
lamivudine
23
Q
What are the preferred PIs as third agent for ART?
A
Atazanavir/ritonavir
or
Darunavir/ritonavir
24
Q
What must be checked before abacavir can be prescribed?
A
HLA B5701 status
25
What is the preferred NNRTI as third agent for ART?
Rilpivirine
26
What are the preferred INSTI as third agent for ART?
```
Dolutegravir
or
Elvitegravir/cobicistat
or
Raltegravir
```
27
What 2 drugs should NOT be used if viral load > 100 000?
Abacavir
or
Rilpivirine
28
In which setting can abacavir be used even if VL >100 000?
in combination with
| DOLUTEGRAVIR
29
What is the alternative NNRTI as third agent for ART?
Efavirenz
30
Why is tenofovir/emtricitabine the preferred NRTI over abacavir/lamivudine?
Less virological FAILURE
EFFECTIVE at higher viral loads (< 100 000)
Less grade 3/4 ADVERSE events
31
Why is tenofovir alafenamide preferred over tenofovir disoproxil?
Less impact on RENAL and BONE
32
Why is Tenofovir alafenamide more likely to have drug-drug interactions than tenofovir disoproxil?
substrate of P-GLYCOPROTEIN
therefore INDUCERS of p-glycoprotein (ie anticonvulsants, st johns wort, rifamycins)
may LOWER TENOFOVIR concentration
33
Why is zidovudine, stavudine or didanosine not recommended first line ART?
TOXICITY
| mitochondrial and hepatic
34
What specific toxicity is associated with zidovudine/lamivudine?
Lipoatrophy
35
In what specific circumstance might zidovudine be given as first line ART?
Pregnancy
36
Can tenofovir DF be used with lamivudine?
Not well studied
| however Delstrigo is TDF/3TC/DOR
37
What are the theoretical benefits of emtricitabine over lamivudine?
longer intracellular HALF LIFE
incorporated more efficiently into PROVIRAL DNA
Greater in vitro POTENCY
38
With which NRTI is mutation M184V/I most associated with?
LAMIVUDINE
| but can also be emtricitabine
39
What might be one factor that accounts for emtricitabine apparently being associated with less emergence of M184V/I than lamivudine?
Lamivudine older drug
HIV outcomes better as newer drugs evolve
ie analyses may not account for which year ART started
40
Why is ritonavir preferred booster for atazanavir c/w cobicistat?
Less resistance if virological failure
41
Which is the preferred PI out of darunavir and atazanavir?
DARUNAVIR
42
What is the benefit of darunavir c/w atazanavir?
less ADVERSE events
43
What is the main ADVERSE event that makes atazanavir less favourable?
Hyperbilirubinaemia/JAUNDICE
| can be stigmatising or distressing but not clinically significant
44
Why is raltegravir preferred over atazanavir?
less ADVERSE events
45
What is the benefit of atazanavir c/w raltegravir?
Less virological FAILURE
| rates of resistance not significantly different
46
What is the benefit of atazanavir c/w efavirenz?
less virological FAILURE
| less RESISTANCE
47
Why is raltegravir preferred over darunavir?
Less ADVERSE events
| less virological FAILURE
48
What is the benefit of darunavir c/w raltegravir?
Less RESISTANCE
| despite more virological failure ?SE related
49
Is there a difference in grade 3 or 4 adverse events between raltegravir and darunavir?
NO
| so darunavir discontinuation due to mild SEs
50
How does dolutegravir compare with raltegravir as ART at initiation?
NON-INFERIOR
51
How does ABC/3TC/dolutegravir compare with TDF/FTC/efavirenz?
dolutegravir SUPERIOR
52
Why is ABC/3TC/dolutegravir superior to TDF/FTC/efavirenz?
less DISCONTINUATION due to adverse events
53
Why is dolutegravir preferred over darunavir?
less ADVERSE events overall
54
What benefit does darunavir have over dolutegravir?
less SERIOUS ADVERSE events
| 5% vs 11%, 1 DTG had suicide attempt with history of suicidal ideation
55
How does elvitegravir/c compare with atazanavir/r or efavirenz?
NON INFERIOR
56
Which drug is associated with MORE development of RESISTANCE in virological failure - elvitegravir/c or atazanavir/r?
ELVITEGRAVIR/c
57
What is the main utility of a elvitegravir containing ART regimen?
available as SINGLE TABLET REGIMEN
58
In what TWO formulation is elvitegravir available?
with either TAF or TDF
TDF/FTC/EVG/c
or
TAF/FTC/EVG/c
59
What is the creatinine clearance cut off for use of tenofovir disoproxil with FTC/EVG/c?
>70ml/min
60
What effect does cobicistat have on serum creatinine?
INHIBIT renal tubular creatinine SECRETION
| modest reduction in Creatinine clearance (10-15 ml/min)
61
How does rilpivirine compare with efavirenz?
NON INFERIOR if viral load <100 000
INFERIOR if viral load > 100 000
Less DISCONTINUATION
62
What is the main reason for efavirenz becoming less favourable as newer agents are developed?
high rate of discontinuation due to ADVERSE EVENTs
63
What is the most common reason for discontinuation of efavirenz?
CNS toxicity
64
What specific CNS effect has been associated with efavirenz?
SUICIDALITY
65
What is an additional common side effect of efavirenz that is more common than with other ART?
adverse impact on LIPIDS
66
When might lopinavir/r be considered as ART?
PI resistance mutations
| contraindication for darunavir
67
Why is nevirapine no longer recommended ART?
small bu serious risk of HEPATIC or CUTANEOUS toxicity
68
Can PI mono therapy be used as initial ART for treatment naive people?
NOT RECOMMENDED
69
Why is PI mono therapy not recommended as initial ART for treatment naive people?
less virological SUPPRESSION
| emergence of PI MUTATIONS
70
If a patient cannot have abacavir or tenofovir (TDF or TAF) as initial ART what can be used?
DARUNAVIR/r + RAL
| if VL <100 000 CD4 >200
71
When can darunavir/r + raltegravir be used as initial ART for the treatment naive?
if tenofovir or abacavir CONTRAINDICATED
VL <100 000
CD4 >200
72
Why is dual therapy with PI + NNRTI not recommended?
more NNRTI-associated RESISTANCE
| Increased grade 3/4 toxicities especially LIPID PROFILE
73
What is low adherence to ART associated with?
drug RESISTANCE
progression to AIDS
DEATH
74
How can non-adherence be categorised?
INTENTIONAL
| UNINTENTIONAL
75
What is UNINTENTIONAL non-adherence?
LIMITATION In capacity or resource that REDUCES ability to ADHERE as intended
76
What is INTENTIONAL non-adherence?
product of decision informed by
| BELIEFS, EMOTIONS, PREFERENCES
77
What is THREE step approach to supporting adherence?
Identify and address:
DOUBTS about personal NEED for ART
specific CONCERNS about taking ART
practical BARRIERS to adherence
78
What pattern of non-adherence to efavirenz was associated with virological failure and resistance?
treatment interruption of cycles of 7 or 28 days
| 2 days off per week no impact
79
Is once daily or twice daily ART regimen associated with improved adherence?
ONCE DAILY
80
Does fixed dose combination for ART improve adherence?
YES (single RCT)
81
What CNS medications can interact with certain ART?
methadone
anti-epileptics
antidepressants
82
What cardiac medications can interact with certain ART?
lipid-lowering agents
| anti arrhythmics
83
What antimicrobial therapy can interact with certain ART?
TB treatment
| antibiotics - clarithromycin or fluconazole
84
What GI medications can interact with certain ART?
acid-reducing agents
| hepatitis C direct acting antivirals
85
What other common classes of medications can interact with ART?
Oral contraceptives
Anti-cancer drugs
Immunosuppressants
Phosphodiesterase inhibitors
86
List THREE DDIs with ART that are absolute contraindications?
Rifampicin + PIs
Proton pump inhibitor + atazanavir
Inhaled corticosteroid + ritonavir/cobicistat
87
What THREE situations might therapeutic drug monitoring be done?
Very limited utility
- identify low adherence
- ensure optimal plasma concentration (eg people with extreme of BMI)
- identifying impact on drug level of DDI
88
What aspect of pharmacokinetics needs to be considered before stopping ART?
Half-life and need for tail or other ART cover
89
What THREE options have been considered for ART stops?
SIMULTANEOUS stop all drugs
STAGGERED stop
REPLACING all drugs with high barrier to resistance
90
Mutations have occurred when stopping ART containing NRTI + NNRTI - what may reduce this risk?
switching to PI mono therapy for 4 weeks
91
Which ART in particular needs special consideration before switch to another regimen?
Efavirenz
92
When is switch from efavirenz most risky?
If VL not suppressed, especially if really initiated therapy
93
Switch EFV to NEVIRAPINE - how is the dosing affected?
NVP TWICE daily dosing for TWO weeks
94
What is the potential risk with more frequent dosing of nevirapine?
Increased risk of hypersensitivity or hepatotoxicity
| not advised if VL detectable
95
What factor increases risk of hypersensitivity or hepatotoxicity if switching to nevirapine?
DETECTABLE viral load
| advised against this
96
Switch EFV to ETRAVIRINE - how is the dosing affected?
No change if VL undetectable
97
Switch EFV to RILPIVIRINE - how is the dosing affected?
No change if VL undetectable
98
What effect does efavirenz have on rilpivirine concentration if switching?
Rilpivirine concentrations lowered by efavirenz for 3-4 weeks
99
Switch EFV to RITONAVIR boosted PI - how is the dosing affected?
No change
100
Switch EFV to RALTEGRAVIR - how is the dosing affected?
No change
101
Switch EFV to MARAVIROC - how is the dosing affected?
DOUBLE dose
600mg TWICE daily
ONE week
102
Switch EFV to ELVITEGRAVIR - how is the dosing affected?
No change
103
Switch EFV to DOLUTEGRAVIR - how is the dosing affected?
No change
104
Switch NEVIRAPINE to RILPIVIRINE - how is the dosing affected?
No change
105
Switch NEVIRAPINE to DOLUTEGRAVIR - how is the dosing affected?
No change
106
Which TWO ART switches may require alteration of doses?
EFAVIRENZ to
- NEVIRAPINE
or
- MARAVIROC
107
Is there any limitations in switching within classes of ART?
NO if no previous resistance mutations
108
What is associated with increased risk of virological failure when switching from PI to NNRTI regimen?
History of treatment failure on NRTI regimen
109
How effective is switching from PI to NNRTI?
EFFECTIVE
| if no history of virological failure or resistance mutations to NRTI or NNRTI
110
What is associated with increased risk of virological failure when switching from PI to RALTEGRAVIR regimen?
History of treatment failure on NRTI regimen
111
How effective is switching from PI to INSTI?
EFFECTIVE
| if no history of virological failure or resistance mutations to TDF or FTC
112
What TWO concerns are there about PI mono therapy?
1) less virological SUPPRESSION
| 2) potential CNS disease
113
What TWO scenarios might PI monotherapy be considered?
1) unable to TOLERATE NRTIs
| 2) BRIDGE in certain clinical scenarios ie stopping NNRTI or acute illness
114
If PI mono therapy is to be given, which TWO PIs can be used?
1) DARUNAVIR/ritonavir
| 2) LOPINAVIR/ritonavir
115
What impact does PI mono therapy on emergence of resistance?
No significant
116
When can boosted PI with lamivudine (DUAL regimen) be considered?
If toxicity with tenofovir-DF or abacavir
117
Why should treatment interruptions not be encouraged?
Higher rate of opportunistic INFECTION
Increased MORTALITY
Higher rate COMORBIDITY (CVD, renal and hepatic)
118
What is the definition of virological FAILURE?
INCOMPLETE virological response
or
confirmed virological REBOUND (>200copies/ml)
119
What is the definition of INCOMPLETE virological RESPONSE?
-TWO consecutive VL>200copies/ml after 24 weeks starting ART
and
-never VL <50 copies/ml
120
What is the definition of virological REBOUND?
failure to maintain VL <50copies/ml
| TWO or more consecutive samples
121
What is the definition of LOW LEVEL VIRAEMIA?
PERSISTENT VL 50-200copies/ml
122
What is the definition of virological BLIP?
SINGLE VL 50-200 copies/ml
| followed by undetectable results
123
What is a likely cause for 'virological blips'?
ASSAY variation and processing ARTEFACT
124
What level of transient detectable viral load is associated with future rebound?
VL >500copies/ml
125
On what ART regimen are changes indicated if low level viraemia?
LOW-GENETIC BARRIER
NNRTI
1st gen INSTI ie RAL
126
What impact does viral load between 20-50copies/ml have on future outcomes? ie in more sensitive assays
Increased risk of REBOUND
| Clinical significance unclear
127
Among drug experienced people on ART who experience virological failure, what proportion have resistance mutations?
30%
128
What is the treatment approach to a person with SIGNIFICANT resistance?
```
TWO, preferably 3, FULLY ACTIVE drugs
include
ONE active PI/r
and
ONE novel agent (INSTI, CCR5 antagonist, fusion inhibitor)
```
129
Out of the PIs which one is preferred in a person with significant resistance?
DARUNAVIR/r
130
Resistance reports - WILD TYPE VIRUS - what does this mean?
NO resistance
131
Resistance reports - M184V or I - what does this mean?
LAMIVUDINE or EMTRICITABINE resistance
132
Resistance reports - K103N - what does this mean?
NNRTI resistance, EFAVIRENZ or NEVIRAPINE
133
Resistance reports - Y181C or I or V - what does this mean?
```
NNRTI resistance (all drugs)
(CAB/RPV contraindicated)
```
134
Resistance reports - E138K - what does this mean?
```
NNRTI resistance (low level)
(CAB/RPV contraindicated)
```
135
Resistance reports - Y143C or R - what does this mean?
INSTI resistance (1st and 2nd generation)
136
Resistance reports - Q148R or H - what does this mean?
INSTI resistance (all drugs)
137
Resistance reports - N155H - what does this mean?
INSTI resistance (all drugs)
138
Resistance reports - K65R - what does this mean?
```
NRTI resistance (abacavir, tenofovir, FTC, 3TC)
increased SUSCEPTIBILITY to AZT
```
139
Resistance reports - L74V - what does this mean?
NRTI resistance, ABACAVIR
140
If a patient has virological failure but no resistance on testing what is the option for treatment?
switch to PI from NNRTI or INSTI
or
re-start failing regimen if poor/non adherence issue
141
If a patient has virological failure and NNRTI resistance on testing what is the option for treatment?
```
switch to INTEGRASE inhibitor
or
PI
or
etravirine (consider)
or
maraviroc
```
142
If a patient has virological failure and NRTI resistance on testing what is the option for treatment?
```
M184V alone - continue TDF/FTC ( weakens virus if FTC present)
Consider alternative ART class if significant NRTI resistance
```
143
If a patient has virological failure and PI resistance on testing what is the option for treatment?
switch to DARUNAVIR
+
INSTI, etravirine or maraviroc
144
If a patient has virological failure and INTEGRASE resistance on testing what is the option for treatment?
switch to PI
or
alternative class
145
What is the definition of extended three drug-class resistance?
absence of fully active
| NRTI, NNRTI, PI
146
What is the risk of 3 drug-class resistance?
2%
147
In 3 drug-class resistance which integrase inhibitor is preferred?
DOLUTEGRAVIR
148
What drugs can be considered in 3 drug-class resistance?
```
PIs
INSTIs
MARAVIROC (CCR5 inhibitor)
Etravirine (NNRTI)
ENFUVIRITIDE (Fusion inhibitor)
```
149
Can NRTIs be used even if existing or potential reverse transcriptase mutations?
YES
| combine with PI (or new data DTG)
150
What drug class if enfuvirtide?
Fusion inhibitor
151
What is the name of the fusion inhibitor ART?
Enfuvirtide
152
How is enfuviritide (fusion inhibitor) administered?
SC injection
153
If a person has triple or multiple class failure and a 3 drug active ART regimen cannot be created, what are the options?
Continue on current therapy
or
research drugs
154
What is the benefit of continuing current ART even if failure and multi-class resistance?
some virological suppression preserves CD4 and improved clinical benefits than if stop treatment
155
Should single active ART be added to a failing multi resistant regimen?
NO
| risk of resistance to that drug/class
156
When should a single active ART be added to a failing multi resistant regimen?
high risk of clinical progression
| eg CD4 <100
157
If a person has integrase resistance and/or triple-class resistance, how should dolutegravir be dosed?
TWICE daily
158
What impact does delaying ART start until after 8 weeks of TB treatment have on people living with co-infection (HIV/TB)?
Increased AIDS
&
DEATH
159
What are the complexities of starting ART at the same time as TB treatment?
large PILL BURDEN
higher rates of TOXICITY
drug-drug INTERACTIONS
IRIS
160
What group of PLW HIV are at lower risk of HIV disease progression over the subsequent 6 months?
CD4 cell count >350cell/count
161
Those with a CD4 count >350cell/count can have ART start deferred until after TB treatment - why?
less risk of HIV progression over 6 month period
162
When should ART be started asap in context of TB treatment?
If CD4 cell count <50 cells
| however may be more practical at <100 cells
163
What should be performed regularly if ART is being started in the context of TB meningitis?
regular CSF PRESSURE measurement
164
How does rifamycins complicated ART prescription?
INTERACT with many agents
| liver enzyme INDUCER
165
What side effects can occur with rifamycins that can also do so with ART?
RASH
| HEPATOXICITY
166
What is the FIRST LINE ART if TB treatment is also indicated?
EFAVIRENZ + NRTI backbone
167
What dosing adjustment is required for EFAVIRENZ when prescribed alongside TB treatment?
STANDARD dose
once daily
No adjustment
168
What impact does rifampicin have on integrase inhibitors?
DECREASE serum levels by 50%
169
What dosing adjustment is required for RALTEGRAVIR when prescribed alongside TB treatment?
STANDARD dose
400mg twice daily
No adjustment
170
What dosing adjustment is required for DOLUTEGRAVIR when prescribed alongside TB treatment?
DOUBLE dose
| 50mg TWICE daily
171
Can PIs be administered alongside standard TB treatment?
NO
172
What impact does rifampicin have on PIs?
DECREASE serum levels below therapeutic target
173
Why can PI dose not be increased to counteract the effect of rifampicin?
increased HEPATOTOXICITY
174
What impact does PI have on RIFABUTIN?
INCREASE concentrations
175
What dosing adjustment is required If RIFABUTIN is being administered with a PI?
REDUCE frequency
176
What dosing adjustment is required If RIFABUTIN is being administered with a dolutegravir or raltegravir?
STANDARD dose
full-dose daily
No adjustment
177
Why can rifamycins not be administered with elvitegravir?
boosted with COBICISTAT
178
Why can rifamycins not be administered with TAF?
INDUCE p-glycoprotein DECREASE tenofovir level
179
Can TAF be used as an alternative to TDF when administered alongside rifamycins?
NO
180
BHIVA - hepatitis B + HIV co-infection - when to treat?
start ART without delay
181
What is the benefit of starting early ART in hepatitis B + HIV co-infection?
to reduce risk of liver-related DEATH
182
In hepatitis B + HIV co-infection, when might it be acceptable to delay ART start until patient ready?
CD4 >500
DNA <2000IU/ml
minimal or no liver inflammation/fibrosis
183
If a person with hepatitis B + HIV co-infection delays ART what monitoring should be performed?
SIX monthly
- HBV DNA and ALT
YEARLY
- fibroscan
184
What TWO agents can be used as part of the regimen to treat both hepatitis B + HIV co-infection?
TENOFOVIR DF or TAF
185
What NRTIs are contraindicated as monotherapy in hepatitis B + HIV co-infection?
LAMIVUDINE
or
EMTRICITABINE
186
Why are lamivudine/emtricitabine contraindicated as monotherapy in hepatitis B + HIV co-infection?
risk of RESISTANCE
187
When can entecavir be used for HBV treatment in hepatitis B + HIV co-infection?
In ADDITION to a fully suppressive ART regimen
| entecavir cannot be used as part of ART regimen
188
What risk is associated with stopping HBV treatment?
FLARE of HBV replication and liver DAMAGE
| SEVERE in cirrhosis
189
BHIVA - hepatitis C + HIV co-infection - when to treat?
start ART before HCV treatment
190
What impact does hepatitis C + HIV co-infection have on clinical outcomes?
ACCELERATED
- fibrosis
- cirrhosis
- liver-related death
- HCC
191
What impact does ART have on clinical outcomes for hepatitis C + HIV co-infection?
SLOWS progression to liver disease
| likely to still be faster than HCV mono-infection
192
What dosing adjustment is required for RIBOVIRIN (HCV treatment) is used alongside ABACAVIR?
WEIGHT-based dose adjustment
193
What considerations should be made before prescribing ART for a person with hepatitis C + HIV co-infection?
Drug-drug interactions if HCV treatment also started
194
When to start ART - HIV + kaposi sarcoma?
PROMPTLY (AIDS-defining malignancy)
195
When to start ART - HIV + non-Hodgkin lymphoma?
PROMPTLY (AIDS-defining malignancy)
196
When to start ART - cervical cancer?
PROMPTLY (AIDS-defining malignancy)
197
When to start ART - CIN2/3?
PROMPTLY
198
What impact does HIV have on CIN2/3?
Higher treatment FAILURE rate than HIV-negative women
199
List THREE AIDS defining malignancies?
Kaposi sarcoma
Non-Hodkins lymphoma (diffuse B cell, Burkitts, primary CNS)
Invasive cervical cancer
200
When to start ART - anal cancer?
If treated with chemo-radiotherapy START
201
When to start ART - Hodgkin lymphoma?
during CHEMOTHERAPY
202
When to start ART - other non-AIDS defining malignancy?
during CHEMOTHERAPY or RADIOTHERAPY
203
In patients starting chemotherapy and with HBcAb positive - what should be included in treatment plan?
Antiviral prophylaxis
| - ie tenofovir
204
What ART should be avoided when planning cytotoxic chemotherapy?
RITONAVIR or COBICISTAT boosted ART
205
Atazanavir is contraindicated in use with chemotherapy irinotecan - why?
Irinotecan METABOLISED by UGT1A1 isoenzymes
Atazanavir INHIBITS UGT1A1
Gilbert syndrome - congenital inhibition of these isoenzymes
Gilbert syndrome + irinotecan resulted in life threatening TOXICITY
206
ART and chemotherapy similar side effects - MYELOSUPPRESSION - which ART to avoid?
ZIDOVUDINE
207
ART and chemotherapy similar side effects - PERIPHERAL NEUROPATHY - which ART to avoid?
STAVUDINE
DIDANOSINE
ZALCITABINE
208
What are the THREE categories of PLW HIV with abnormal neuropsychological testing results?
1) HIV-associated asymptomatic neurocognitive impairment
2) HIV-associated mild neurocognitive disorder
3) HIV-associated dementia
209
What is the difference between HIV- associated asymptomatic neurocognitive impairment, mild neurocognitive disorder and dementia?
asymptomatic - abnormal neuropsychological testing but NO symptoms or impact on ADLs
mild - abnormal neuropsychological testing with MILD symptoms or impact on ADLs
dementia - abnormal neuropsychological testing with SEVERE symptoms or impact on ADLs
210
What impact does CD4 cell count have on neurocognitive function in PLW HIV?
low NADIR CD4 associated with neurocognitive IMPAIRMENT
211
What ART should be avoided in a person with HIV-associated neurocognitive disorders?
EFAVIRENZ
212
Which class of ART has been associated with a reduced risk of severe HIV-associated dementia?
NRTI
213
What is a CPE score of ART?
Clinical penetration effectiveness
| - score that reflects cerebral effects of individual ART
214
Why is efavirenz ideally avoided in HIV-associated neurocognitive disorders?
less improvement in cognitive function
quicker time to cognitive impairment
switch to non-EFV ART improved CNS symptoms
215
What is the reason for assessment of CSF HIV RNA in people with HIV-associated neurocognitive disorders?
CSF HIV RNA - can be detectable despite undetectable plasma
| Genetic DIVERSITY between CSF and plasma HIV including potential for resistance
216
Who is at higher risk of HIV-associated nephropathy?
Black people
LOW CD4
DETECTABLE VL
217
When to start ART - HIV-associated nephropathy?
IMMEDIATELY
218
What kidney disease is HIV replication a risk factor for?
Immune-complex kidney disease (eg IgA nephropathy)
219
What impact does ART treatment have on kidney transplantation outcomes for PLW HIV and CKD?
EXCELLENT outcomes
| if VL undetectable and CD4 >200
220
What ART is contraindicated if eGFR < 60ml/min?
TENOFOVIR DF
+
ATAZANAVIR
221
Which NRTI does not need dose adjustment in impaired renal function?
ABACAVIR
222
Does adjustment for NRTIs is required at what eGFR?
<50 ml/min
223
Does adjustment for MARAVIROC is required at what eGFR?
<80ml/min
224
What ART increases risk of nephrolithiasis (renal calculi)?
ATAZANAVIR
225
What HIV specific factors contribute to the increased risk of cardiovascular disease?
VIRAEMIA
immune DYSFUNCTION
pro-INFLAMMATORY state
226
When assessing CVD risk with QRISK, what correction can be added to reflect risk associated with HIV?
x1.6
227
What impact does hepatitis C co-infection have on CVD risk in PLW HIV?
UNCLEAR
| possible association with acute coronary events (ACS) and STROKE
228
What impact do PIs have on CVD risk?
```
INCREASED if PI:
LOPINAVIR
or
INDINAVIR
or
FOSAMPRENAVIR
```
229
Which NRTI is preferred in people with raised CVD risk?
TENOFOVIR DF
230
What is the potential benefit of INSTIs in those with high CVD risk?
NO effect on plasma lipids
231
Which ART is associated with postural hypotension?
MARAVIROC
232
What effect may ART have on high-density lipoprotein (HDL)?
LESS stable
| bind LESS well to hepatocyte receptors
233
Which NNRTI has the biggest negative impact on lipid profile?
EFAVIRENZ
234
Which NNRTI has a potentially beneficial impact on lipid profile?
RILPIVIRINE
235
WOMEN + ART - what side effects are they more likely report?
LIPODYSTROPHY
RASH
NAUSEA
236
WOMEN + ART - what proportion of women vs men are likely to discontinue ART within the first year?
19% vs 11%
237
What patient group are more at risk fo CNS effects from EFAVIRENZ?
Africans
238
Why are African people more at risk of CNS effects from EFAVIRENZ?
variant in CYP2B6
239
WOMEN + ART - what impact does being female have on side effects associated with NEVIRAPINE?
increased
- RASH
- HEPATOTOXICITY
240
WOMEN + ART - Are women or men more likely to have poor adherence to ART?
WOMEN
241
WOMEN + ART - which ART is the only one to have licence for use in pregnancy?
ZIDOVUDINE
242
WOMEN + ART - how many prospective reports on ART in pregnancy are required before impact on congenital outcomes can be assessed?
200
243
WOMEN + ART - for which ART is there sufficient reports to suggest no increased risk of congenital abnormality?
```
abacavir
zidovudine
tenofovir DF
emtricitabine
lamivudine
atazanavir
darunavir
lopinavir
ritonavir
efavirenz
nevirapine
```
244
What impact does efavirenz have on levonorgestrel?
REDUCES levonorgestrel concentrations
245
What is the risk of severe depression or suicidal ideation in people prescribed efavirenz with a past history of mental illness?
2%
246
How does risk of suicidality compare between those on efavirenz vs not on efavirenz?
8/1000 vs 4/1000
247
What dose adjustment of EFAVIRENZ is recommended in YOUNG PEOPLE?
AVOID standard dose (600mg OD) if:
weight <50kg
AND
history of mental illness
248
What impact does being a YOUNG PERSON have on ART ADHERENCE?
reduced adherence
249
What proportion of YOUNG PEOPLE are TRIPLE-CLASS EXPERIENCED?
50%
250
Which tenofovir formulation is preferred in people with osteoporosis or high risk (>20% FRAX) of fragility fracture?
Tenofovir ALAFENAMIDE (TAF)
251
In addition to TDF which ART drug class is associated with low bone mineral density?
protease inhibitors
252
Is there benefit in switching from PIs if low bone mineral density?
NO evidence
253
Which ART has been associated with vitamin D deficiency?
EFAVIRENZ
254
Which ART class has been associated with AVASCULAR NECROSIS?
PI
255
What effect does older age have on CD4 cell count?
FASTER DECLINE if not on ART
256
What effect does older age have on recovery of CD4 cell count once ART started?
LIMITED recovery
257
What is the hypothesis for more limited recovery of CD4 cell count in older age once ART started?
THYMIC DYSFUNCTION
| lower NADIR CD4 cell count
258
To which ART class is exposure increased with age?
Boosted PIs
