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HIV treatment Flashcards

1
Q

What is the primary aim of treatment of HIV?

A

PREVENT
- mortality
&
- morbidity

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2
Q

What are the secondary aims of treatment of HIV?

A

improve LIFE EXPECTANCY

Reduction of sexual TRANSMISSION

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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

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4
Q

What is are the negative impacts of depression on HIV care?

A

associated with:
poor ADHERENCE
MORTALITY

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5
Q

What is a useful QUICK screening tool for depression?

A

Arroll test

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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?
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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
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8
Q

START trial - What was the relative risk reduction of immediate ART start vs deferred ART on morbidity and mortality?

A

57%

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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%

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10
Q

What study results guide initiation of ART in context of AIDS defining infection?

A

ACTG 5164

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11
Q

What study results guide initiation of ART in context of asymptomatic chronic HIV infection infection?

A

START

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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

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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

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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

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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

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16
Q

Why should ART not be interrupted?

A

Increased all-cause MORTALITY (SMART study)

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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
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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

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19
Q

How quickly is virological suppression achieved after ART initiation?

A

3-6 months

INSTIs 1-3 months

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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

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21
Q

What is the preferred NRTI back bone for ART?

A

Tenofovir disoproxil (or alafenamide)
+
emtricitibine

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22
Q

What is the alternative NRTI back bone for ART?

A

abacavir
+
lamivudine

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23
Q

What are the preferred PIs as third agent for ART?

A

Atazanavir/ritonavir
or
Darunavir/ritonavir

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24
Q

What must be checked before abacavir can be prescribed?

A

HLA B5701 status

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25
Q

What is the preferred NNRTI as third agent for ART?

A

Rilpivirine

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26
Q

What are the preferred INSTI as third agent for ART?

A 
Dolutegravir
or
Elvitegravir/cobicistat
or
Raltegravir
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27
Q

What 2 drugs should NOT be used if viral load > 100 000?

A

Abacavir
or
Rilpivirine

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28
Q

In which setting can abacavir be used even if VL >100 000?

A

in combination with

DOLUTEGRAVIR

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29
Q

What is the alternative NNRTI as third agent for ART?

A

Efavirenz

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30
Q

Why is tenofovir/emtricitabine the preferred NRTI over abacavir/lamivudine?

A

Less virological FAILURE
EFFECTIVE at higher viral loads (< 100 000)
Less grade 3/4 ADVERSE events

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31
Q

Why is tenofovir alafenamide preferred over tenofovir disoproxil?

A

Less impact on RENAL and BONE

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32
Q

Why is Tenofovir alafenamide more likely to have drug-drug interactions than tenofovir disoproxil?

A

substrate of P-GLYCOPROTEIN
therefore INDUCERS of p-glycoprotein (ie anticonvulsants, st johns wort, rifamycins)
may LOWER TENOFOVIR concentration

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33
Q

Why is zidovudine, stavudine or didanosine not recommended first line ART?

A

TOXICITY

mitochondrial and hepatic

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34
Q

What specific toxicity is associated with zidovudine/lamivudine?

A

Lipoatrophy

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35
Q

In what specific circumstance might zidovudine be given as first line ART?

A

Pregnancy

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36
Q

Can tenofovir DF be used with lamivudine?

A

Not well studied

however Delstrigo is TDF/3TC/DOR

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37
Q

What are the theoretical benefits of emtricitabine over lamivudine?

A

longer intracellular HALF LIFE
incorporated more efficiently into PROVIRAL DNA
Greater in vitro POTENCY

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38
Q

With which NRTI is mutation M184V/I most associated with?

A

LAMIVUDINE

but can also be emtricitabine

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39
Q

What might be one factor that accounts for emtricitabine apparently being associated with less emergence of M184V/I than lamivudine?

A

Lamivudine older drug
HIV outcomes better as newer drugs evolve
ie analyses may not account for which year ART started

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40
Q

Why is ritonavir preferred booster for atazanavir c/w cobicistat?

A

Less resistance if virological failure

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41
Q

Which is the preferred PI out of darunavir and atazanavir?

A

DARUNAVIR

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42
Q

What is the benefit of darunavir c/w atazanavir?

A

less ADVERSE events

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43
Q

What is the main ADVERSE event that makes atazanavir less favourable?

A

Hyperbilirubinaemia/JAUNDICE

can be stigmatising or distressing but not clinically significant

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44
Q

Why is raltegravir preferred over atazanavir?

A

less ADVERSE events

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45
Q

What is the benefit of atazanavir c/w raltegravir?

A

Less virological FAILURE

rates of resistance not significantly different

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46
Q

What is the benefit of atazanavir c/w efavirenz?

A

less virological FAILURE

less RESISTANCE

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47
Q

Why is raltegravir preferred over darunavir?

A

Less ADVERSE events

less virological FAILURE

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48
Q

What is the benefit of darunavir c/w raltegravir?

A

Less RESISTANCE

despite more virological failure ?SE related

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49
Q

Is there a difference in grade 3 or 4 adverse events between raltegravir and darunavir?

A

NO

so darunavir discontinuation due to mild SEs

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50
Q

How does dolutegravir compare with raltegravir as ART at initiation?

A

NON-INFERIOR

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51
Q

How does ABC/3TC/dolutegravir compare with TDF/FTC/efavirenz?

A

dolutegravir SUPERIOR

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52
Q

Why is ABC/3TC/dolutegravir superior to TDF/FTC/efavirenz?

A

less DISCONTINUATION due to adverse events

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53
Q

Why is dolutegravir preferred over darunavir?

A

less ADVERSE events overall

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54
Q

What benefit does darunavir have over dolutegravir?

A

less SERIOUS ADVERSE events

5% vs 11%, 1 DTG had suicide attempt with history of suicidal ideation

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55
Q

How does elvitegravir/c compare with atazanavir/r or efavirenz?

A

NON INFERIOR

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56
Q

Which drug is associated with MORE development of RESISTANCE in virological failure - elvitegravir/c or atazanavir/r?

A

ELVITEGRAVIR/c

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57
Q

What is the main utility of a elvitegravir containing ART regimen?

A

available as SINGLE TABLET REGIMEN

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58
Q

In what TWO formulation is elvitegravir available?

A

with either TAF or TDF
TDF/FTC/EVG/c
or
TAF/FTC/EVG/c

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59
Q

What is the creatinine clearance cut off for use of tenofovir disoproxil with FTC/EVG/c?

A

> 70ml/min

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60
Q

What effect does cobicistat have on serum creatinine?

A

INHIBIT renal tubular creatinine SECRETION

modest reduction in Creatinine clearance (10-15 ml/min)

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61
Q

How does rilpivirine compare with efavirenz?

A

NON INFERIOR if viral load <100 000
INFERIOR if viral load > 100 000
Less DISCONTINUATION

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62
Q

What is the main reason for efavirenz becoming less favourable as newer agents are developed?

A

high rate of discontinuation due to ADVERSE EVENTs

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63
Q

What is the most common reason for discontinuation of efavirenz?

A

CNS toxicity

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64
Q

What specific CNS effect has been associated with efavirenz?

A

SUICIDALITY

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65
Q

What is an additional common side effect of efavirenz that is more common than with other ART?

A

adverse impact on LIPIDS

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66
Q

When might lopinavir/r be considered as ART?

A

PI resistance mutations

contraindication for darunavir

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67
Q

Why is nevirapine no longer recommended ART?

A

small bu serious risk of HEPATIC or CUTANEOUS toxicity

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68
Q

Can PI mono therapy be used as initial ART for treatment naive people?

A

NOT RECOMMENDED

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69
Q

Why is PI mono therapy not recommended as initial ART for treatment naive people?

A

less virological SUPPRESSION

emergence of PI MUTATIONS

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70
Q

If a patient cannot have abacavir or tenofovir (TDF or TAF) as initial ART what can be used?

A

DARUNAVIR/r + RAL

if VL <100 000 CD4 >200

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71
Q

When can darunavir/r + raltegravir be used as initial ART for the treatment naive?

A

if tenofovir or abacavir CONTRAINDICATED
VL <100 000
CD4 >200

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72
Q

Why is dual therapy with PI + NNRTI not recommended?

A

more NNRTI-associated RESISTANCE

Increased grade 3/4 toxicities especially LIPID PROFILE

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73
Q

What is low adherence to ART associated with?

A

drug RESISTANCE
progression to AIDS
DEATH

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74
Q

How can non-adherence be categorised?

A

INTENTIONAL

UNINTENTIONAL

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75
Q

What is UNINTENTIONAL non-adherence?

A

LIMITATION In capacity or resource that REDUCES ability to ADHERE as intended

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76
Q

What is INTENTIONAL non-adherence?

A

product of decision informed by

BELIEFS, EMOTIONS, PREFERENCES

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77
Q

What is THREE step approach to supporting adherence?

A

Identify and address:
DOUBTS about personal NEED for ART
specific CONCERNS about taking ART
practical BARRIERS to adherence

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78
Q

What pattern of non-adherence to efavirenz was associated with virological failure and resistance?

A

treatment interruption of cycles of 7 or 28 days

2 days off per week no impact

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79
Q

Is once daily or twice daily ART regimen associated with improved adherence?

A

ONCE DAILY

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80
Q

Does fixed dose combination for ART improve adherence?

A

YES (single RCT)

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81
Q

What CNS medications can interact with certain ART?

A

methadone
anti-epileptics
antidepressants

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82
Q

What cardiac medications can interact with certain ART?

A

lipid-lowering agents

anti arrhythmics

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83
Q

What antimicrobial therapy can interact with certain ART?

A

TB treatment

antibiotics - clarithromycin or fluconazole

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84
Q

What GI medications can interact with certain ART?

A

acid-reducing agents

hepatitis C direct acting antivirals

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85
Q

What other common classes of medications can interact with ART?

A

Oral contraceptives
Anti-cancer drugs
Immunosuppressants
Phosphodiesterase inhibitors

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86
Q

List THREE DDIs with ART that are absolute contraindications?

A

Rifampicin + PIs
Proton pump inhibitor + atazanavir
Inhaled corticosteroid + ritonavir/cobicistat

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87
Q

What THREE situations might therapeutic drug monitoring be done?

A

Very limited utility

  • identify low adherence
  • ensure optimal plasma concentration (eg people with extreme of BMI)
  • identifying impact on drug level of DDI
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88
Q

What aspect of pharmacokinetics needs to be considered before stopping ART?

A

Half-life and need for tail or other ART cover

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89
Q

What THREE options have been considered for ART stops?

A

SIMULTANEOUS stop all drugs
STAGGERED stop
REPLACING all drugs with high barrier to resistance

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90
Q

Mutations have occurred when stopping ART containing NRTI + NNRTI - what may reduce this risk?

A

switching to PI mono therapy for 4 weeks

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91
Q

Which ART in particular needs special consideration before switch to another regimen?

A

Efavirenz

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92
Q

When is switch from efavirenz most risky?

A

If VL not suppressed, especially if really initiated therapy

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93
Q

Switch EFV to NEVIRAPINE - how is the dosing affected?

A

NVP TWICE daily dosing for TWO weeks

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94
Q

What is the potential risk with more frequent dosing of nevirapine?

A

Increased risk of hypersensitivity or hepatotoxicity

not advised if VL detectable

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95
Q

What factor increases risk of hypersensitivity or hepatotoxicity if switching to nevirapine?

A

DETECTABLE viral load

advised against this

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96
Q

Switch EFV to ETRAVIRINE - how is the dosing affected?

A

No change if VL undetectable

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97
Q

Switch EFV to RILPIVIRINE - how is the dosing affected?

A

No change if VL undetectable

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98
Q

What effect does efavirenz have on rilpivirine concentration if switching?

A

Rilpivirine concentrations lowered by efavirenz for 3-4 weeks

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99
Q

Switch EFV to RITONAVIR boosted PI - how is the dosing affected?

A

No change

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100
Q

Switch EFV to RALTEGRAVIR - how is the dosing affected?

A

No change

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101
Q

Switch EFV to MARAVIROC - how is the dosing affected?

A

DOUBLE dose
600mg TWICE daily
ONE week

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102
Q

Switch EFV to ELVITEGRAVIR - how is the dosing affected?

A

No change

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103
Q

Switch EFV to DOLUTEGRAVIR - how is the dosing affected?

A

No change

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104
Q

Switch NEVIRAPINE to RILPIVIRINE - how is the dosing affected?

105
Q

Switch NEVIRAPINE to DOLUTEGRAVIR - how is the dosing affected?

106
Q

Which TWO ART switches may require alteration of doses?

A

EFAVIRENZ to
- NEVIRAPINE
or
- MARAVIROC

107
Q

Is there any limitations in switching within classes of ART?

A

NO if no previous resistance mutations

108
Q

What is associated with increased risk of virological failure when switching from PI to NNRTI regimen?

A

History of treatment failure on NRTI regimen

109
Q

How effective is switching from PI to NNRTI?

A

EFFECTIVE

if no history of virological failure or resistance mutations to NRTI or NNRTI

110
Q

What is associated with increased risk of virological failure when switching from PI to RALTEGRAVIR regimen?

A

History of treatment failure on NRTI regimen

111
Q

How effective is switching from PI to INSTI?

A

EFFECTIVE

if no history of virological failure or resistance mutations to TDF or FTC

112
Q

What TWO concerns are there about PI mono therapy?

A

1) less virological SUPPRESSION

2) potential CNS disease

113
Q

What TWO scenarios might PI monotherapy be considered?

A

1) unable to TOLERATE NRTIs

2) BRIDGE in certain clinical scenarios ie stopping NNRTI or acute illness

114
Q

If PI mono therapy is to be given, which TWO PIs can be used?

A

1) DARUNAVIR/ritonavir

2) LOPINAVIR/ritonavir

115
Q

What impact does PI mono therapy on emergence of resistance?

A

No significant

116
Q

When can boosted PI with lamivudine (DUAL regimen) be considered?

A

If toxicity with tenofovir-DF or abacavir

117
Q

Why should treatment interruptions not be encouraged?

A

Higher rate of opportunistic INFECTION
Increased MORTALITY
Higher rate COMORBIDITY (CVD, renal and hepatic)

118
Q

What is the definition of virological FAILURE?

A

INCOMPLETE virological response
or
confirmed virological REBOUND (>200copies/ml)

119
Q

What is the definition of INCOMPLETE virological RESPONSE?

A

-TWO consecutive VL>200copies/ml after 24 weeks starting ART
and
-never VL <50 copies/ml

120
Q

What is the definition of virological REBOUND?

A

failure to maintain VL <50copies/ml

TWO or more consecutive samples

121
Q

What is the definition of LOW LEVEL VIRAEMIA?

A

PERSISTENT VL 50-200copies/ml

122
Q

What is the definition of virological BLIP?

A

SINGLE VL 50-200 copies/ml

followed by undetectable results

123
Q

What is a likely cause for ‘virological blips’?

A

ASSAY variation and processing ARTEFACT

124
Q

What level of transient detectable viral load is associated with future rebound?

A

VL >500copies/ml

125
Q

On what ART regimen are changes indicated if low level viraemia?

A

LOW-GENETIC BARRIER
NNRTI
1st gen INSTI ie RAL

126
Q

What impact does viral load between 20-50copies/ml have on future outcomes? ie in more sensitive assays

A

Increased risk of REBOUND

Clinical significance unclear

127
Q

Among drug experienced people on ART who experience virological failure, what proportion have resistance mutations?

128
Q

What is the treatment approach to a person with SIGNIFICANT resistance?

A 
TWO, preferably 3, FULLY ACTIVE drugs
include
ONE active PI/r 
and
ONE novel agent (INSTI, CCR5 antagonist, fusion inhibitor)
129
Q

Out of the PIs which one is preferred in a person with significant resistance?

A

DARUNAVIR/r

130
Q

Resistance reports - WILD TYPE VIRUS - what does this mean?

A

NO resistance

131
Q

Resistance reports - M184V or I - what does this mean?

A

LAMIVUDINE or EMTRICITABINE resistance

132
Q

Resistance reports - K103N - what does this mean?

A

NNRTI resistance, EFAVIRENZ or NEVIRAPINE

133
Q

Resistance reports - Y181C or I or V - what does this mean?

A 
NNRTI resistance (all drugs)
(CAB/RPV contraindicated)
134
Q

Resistance reports - E138K - what does this mean?

A 
NNRTI resistance (low level)
(CAB/RPV contraindicated)
135
Q

Resistance reports - Y143C or R - what does this mean?

A

INSTI resistance (1st and 2nd generation)

136
Q

Resistance reports - Q148R or H - what does this mean?

A

INSTI resistance (all drugs)

137
Q

Resistance reports - N155H - what does this mean?

A

INSTI resistance (all drugs)

138
Q

Resistance reports - K65R - what does this mean?

A 
NRTI resistance (abacavir, tenofovir, FTC, 3TC)
increased SUSCEPTIBILITY to AZT
139
Q

Resistance reports - L74V - what does this mean?

A

NRTI resistance, ABACAVIR

140
Q

If a patient has virological failure but no resistance on testing what is the option for treatment?

A

switch to PI from NNRTI or INSTI
or
re-start failing regimen if poor/non adherence issue

141
Q

If a patient has virological failure and NNRTI resistance on testing what is the option for treatment?

A 
switch to INTEGRASE inhibitor
or 
PI
or
etravirine (consider)
or
maraviroc
142
Q

If a patient has virological failure and NRTI resistance on testing what is the option for treatment?

A 
M184V alone - continue TDF/FTC ( weakens virus if FTC present)
Consider alternative ART class if significant NRTI resistance
143
Q

If a patient has virological failure and PI resistance on testing what is the option for treatment?

A

switch to DARUNAVIR
+
INSTI, etravirine or maraviroc

144
Q

If a patient has virological failure and INTEGRASE resistance on testing what is the option for treatment?

A

switch to PI
or
alternative class

145
Q

What is the definition of extended three drug-class resistance?

A

absence of fully active

NRTI, NNRTI, PI

146
Q

What is the risk of 3 drug-class resistance?

147
Q

In 3 drug-class resistance which integrase inhibitor is preferred?

A

DOLUTEGRAVIR

148
Q

What drugs can be considered in 3 drug-class resistance?

A 
PIs
INSTIs
MARAVIROC (CCR5 inhibitor)
Etravirine (NNRTI)
ENFUVIRITIDE (Fusion inhibitor)
149
Q

Can NRTIs be used even if existing or potential reverse transcriptase mutations?

A

YES

combine with PI (or new data DTG)

150
Q

What drug class if enfuvirtide?

A

Fusion inhibitor

151
Q

What is the name of the fusion inhibitor ART?

A

Enfuvirtide

152
Q

How is enfuviritide (fusion inhibitor) administered?

A

SC injection

153
Q

If a person has triple or multiple class failure and a 3 drug active ART regimen cannot be created, what are the options?

A

Continue on current therapy
or
research drugs

154
Q

What is the benefit of continuing current ART even if failure and multi-class resistance?

A

some virological suppression preserves CD4 and improved clinical benefits than if stop treatment

155
Q

Should single active ART be added to a failing multi resistant regimen?

A

NO

risk of resistance to that drug/class

156
Q

When should a single active ART be added to a failing multi resistant regimen?

A

high risk of clinical progression

eg CD4 <100

157
Q

If a person has integrase resistance and/or triple-class resistance, how should dolutegravir be dosed?

A

TWICE daily

158
Q

What impact does delaying ART start until after 8 weeks of TB treatment have on people living with co-infection (HIV/TB)?

A

Increased AIDS
&
DEATH

159
Q

What are the complexities of starting ART at the same time as TB treatment?

A

large PILL BURDEN
higher rates of TOXICITY
drug-drug INTERACTIONS
IRIS

160
Q

What group of PLW HIV are at lower risk of HIV disease progression over the subsequent 6 months?

A

CD4 cell count >350cell/count

161
Q

Those with a CD4 count >350cell/count can have ART start deferred until after TB treatment - why?

A

less risk of HIV progression over 6 month period

162
Q

When should ART be started asap in context of TB treatment?

A

If CD4 cell count <50 cells

however may be more practical at <100 cells

163
Q

What should be performed regularly if ART is being started in the context of TB meningitis?

A

regular CSF PRESSURE measurement

164
Q

How does rifamycins complicated ART prescription?

A

INTERACT with many agents

liver enzyme INDUCER

165
Q

What side effects can occur with rifamycins that can also do so with ART?

A

RASH

HEPATOXICITY

166
Q

What is the FIRST LINE ART if TB treatment is also indicated?

A

EFAVIRENZ + NRTI backbone

167
Q

What dosing adjustment is required for EFAVIRENZ when prescribed alongside TB treatment?

A

STANDARD dose
once daily
No adjustment

168
Q

What impact does rifampicin have on integrase inhibitors?

A

DECREASE serum levels by 50%

169
Q

What dosing adjustment is required for RALTEGRAVIR when prescribed alongside TB treatment?

A

STANDARD dose
400mg twice daily
No adjustment

170
Q

What dosing adjustment is required for DOLUTEGRAVIR when prescribed alongside TB treatment?

A

DOUBLE dose

50mg TWICE daily

171
Q

Can PIs be administered alongside standard TB treatment?

172
Q

What impact does rifampicin have on PIs?

A

DECREASE serum levels below therapeutic target

173
Q

Why can PI dose not be increased to counteract the effect of rifampicin?

A

increased HEPATOTOXICITY

174
Q

What impact does PI have on RIFABUTIN?

A

INCREASE concentrations

175
Q

What dosing adjustment is required If RIFABUTIN is being administered with a PI?

A

REDUCE frequency

176
Q

What dosing adjustment is required If RIFABUTIN is being administered with a dolutegravir or raltegravir?

A

STANDARD dose
full-dose daily
No adjustment

177
Q

Why can rifamycins not be administered with elvitegravir?

A

boosted with COBICISTAT

178
Q

Why can rifamycins not be administered with TAF?

A

INDUCE p-glycoprotein DECREASE tenofovir level

179
Q

Can TAF be used as an alternative to TDF when administered alongside rifamycins?

180
Q

BHIVA - hepatitis B + HIV co-infection - when to treat?

A

start ART without delay

181
Q

What is the benefit of starting early ART in hepatitis B + HIV co-infection?

A

to reduce risk of liver-related DEATH

182
Q

In hepatitis B + HIV co-infection, when might it be acceptable to delay ART start until patient ready?

A

CD4 >500
DNA <2000IU/ml
minimal or no liver inflammation/fibrosis

183
Q

If a person with hepatitis B + HIV co-infection delays ART what monitoring should be performed?

A

SIX monthly
- HBV DNA and ALT
YEARLY
- fibroscan

184
Q

What TWO agents can be used as part of the regimen to treat both hepatitis B + HIV co-infection?

A

TENOFOVIR DF or TAF

185
Q

What NRTIs are contraindicated as monotherapy in hepatitis B + HIV co-infection?

A

LAMIVUDINE
or
EMTRICITABINE

186
Q

Why are lamivudine/emtricitabine contraindicated as monotherapy in hepatitis B + HIV co-infection?

A

risk of RESISTANCE

187
Q

When can entecavir be used for HBV treatment in hepatitis B + HIV co-infection?

A

In ADDITION to a fully suppressive ART regimen

entecavir cannot be used as part of ART regimen

188
Q

What risk is associated with stopping HBV treatment?

A

FLARE of HBV replication and liver DAMAGE

SEVERE in cirrhosis

189
Q

BHIVA - hepatitis C + HIV co-infection - when to treat?

A

start ART before HCV treatment

190
Q

What impact does hepatitis C + HIV co-infection have on clinical outcomes?

A

ACCELERATED

  • fibrosis
  • cirrhosis
  • liver-related death
  • HCC
191
Q

What impact does ART have on clinical outcomes for hepatitis C + HIV co-infection?

A

SLOWS progression to liver disease

likely to still be faster than HCV mono-infection

192
Q

What dosing adjustment is required for RIBOVIRIN (HCV treatment) is used alongside ABACAVIR?

A

WEIGHT-based dose adjustment

193
Q

What considerations should be made before prescribing ART for a person with hepatitis C + HIV co-infection?

A

Drug-drug interactions if HCV treatment also started

194
Q

When to start ART - HIV + kaposi sarcoma?

A

PROMPTLY (AIDS-defining malignancy)

195
Q

When to start ART - HIV + non-Hodgkin lymphoma?

A

PROMPTLY (AIDS-defining malignancy)

196
Q

When to start ART - cervical cancer?

A

PROMPTLY (AIDS-defining malignancy)

197
Q

When to start ART - CIN2/3?

198
Q

What impact does HIV have on CIN2/3?

A

Higher treatment FAILURE rate than HIV-negative women

199
Q

List THREE AIDS defining malignancies?

A

Kaposi sarcoma
Non-Hodkins lymphoma (diffuse B cell, Burkitts, primary CNS)
Invasive cervical cancer

200
Q

When to start ART - anal cancer?

A

If treated with chemo-radiotherapy START

201
Q

When to start ART - Hodgkin lymphoma?

A

during CHEMOTHERAPY

202
Q

When to start ART - other non-AIDS defining malignancy?

A

during CHEMOTHERAPY or RADIOTHERAPY

203
Q

In patients starting chemotherapy and with HBcAb positive - what should be included in treatment plan?

A

Antiviral prophylaxis

- ie tenofovir

204
Q

What ART should be avoided when planning cytotoxic chemotherapy?

A

RITONAVIR or COBICISTAT boosted ART

205
Q

Atazanavir is contraindicated in use with chemotherapy irinotecan - why?

A

Irinotecan METABOLISED by UGT1A1 isoenzymes
Atazanavir INHIBITS UGT1A1
Gilbert syndrome - congenital inhibition of these isoenzymes
Gilbert syndrome + irinotecan resulted in life threatening TOXICITY

206
Q

ART and chemotherapy similar side effects - MYELOSUPPRESSION - which ART to avoid?

A

ZIDOVUDINE

207
Q

ART and chemotherapy similar side effects - PERIPHERAL NEUROPATHY - which ART to avoid?

A

STAVUDINE
DIDANOSINE
ZALCITABINE

208
Q

What are the THREE categories of PLW HIV with abnormal neuropsychological testing results?

A

1) HIV-associated asymptomatic neurocognitive impairment
2) HIV-associated mild neurocognitive disorder
3) HIV-associated dementia

209
Q

What is the difference between HIV- associated asymptomatic neurocognitive impairment, mild neurocognitive disorder and dementia?

A

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
Q

What impact does CD4 cell count have on neurocognitive function in PLW HIV?

A

low NADIR CD4 associated with neurocognitive IMPAIRMENT

211
Q

What ART should be avoided in a person with HIV-associated neurocognitive disorders?

212
Q

Which class of ART has been associated with a reduced risk of severe HIV-associated dementia?

213
Q

What is a CPE score of ART?

A

Clinical penetration effectiveness

- score that reflects cerebral effects of individual ART

214
Q

Why is efavirenz ideally avoided in HIV-associated neurocognitive disorders?

A

less improvement in cognitive function
quicker time to cognitive impairment
switch to non-EFV ART improved CNS symptoms

215
Q

What is the reason for assessment of CSF HIV RNA in people with HIV-associated neurocognitive disorders?

A

CSF HIV RNA - can be detectable despite undetectable plasma

Genetic DIVERSITY between CSF and plasma HIV including potential for resistance

216
Q

Who is at higher risk of HIV-associated nephropathy?

A

Black people
LOW CD4
DETECTABLE VL

217
Q

When to start ART - HIV-associated nephropathy?

A

IMMEDIATELY

218
Q

What kidney disease is HIV replication a risk factor for?

A

Immune-complex kidney disease (eg IgA nephropathy)

219
Q

What impact does ART treatment have on kidney transplantation outcomes for PLW HIV and CKD?

A

EXCELLENT outcomes

if VL undetectable and CD4 >200

220
Q

What ART is contraindicated if eGFR < 60ml/min?

A

TENOFOVIR DF
+
ATAZANAVIR

221
Q

Which NRTI does not need dose adjustment in impaired renal function?

222
Q

Does adjustment for NRTIs is required at what eGFR?

A

<50 ml/min

223
Q

Does adjustment for MARAVIROC is required at what eGFR?

224
Q

What ART increases risk of nephrolithiasis (renal calculi)?

A

ATAZANAVIR

225
Q

What HIV specific factors contribute to the increased risk of cardiovascular disease?

A

VIRAEMIA
immune DYSFUNCTION
pro-INFLAMMATORY state

226
Q

When assessing CVD risk with QRISK, what correction can be added to reflect risk associated with HIV?

227
Q

What impact does hepatitis C co-infection have on CVD risk in PLW HIV?

A

UNCLEAR

possible association with acute coronary events (ACS) and STROKE

228
Q

What impact do PIs have on CVD risk?

A 
INCREASED if PI:
LOPINAVIR
or
INDINAVIR
or 
FOSAMPRENAVIR
229
Q

Which NRTI is preferred in people with raised CVD risk?

A

TENOFOVIR DF

230
Q

What is the potential benefit of INSTIs in those with high CVD risk?

A

NO effect on plasma lipids

231
Q

Which ART is associated with postural hypotension?

232
Q

What effect may ART have on high-density lipoprotein (HDL)?

A

LESS stable

bind LESS well to hepatocyte receptors

233
Q

Which NNRTI has the biggest negative impact on lipid profile?

234
Q

Which NNRTI has a potentially beneficial impact on lipid profile?

A

RILPIVIRINE

235
Q

WOMEN + ART - what side effects are they more likely report?

A

LIPODYSTROPHY
RASH
NAUSEA

236
Q

WOMEN + ART - what proportion of women vs men are likely to discontinue ART within the first year?

A

19% vs 11%

237
Q

What patient group are more at risk fo CNS effects from EFAVIRENZ?

238
Q

Why are African people more at risk of CNS effects from EFAVIRENZ?

A

variant in CYP2B6

239
Q

WOMEN + ART - what impact does being female have on side effects associated with NEVIRAPINE?

A

increased

  • RASH
  • HEPATOTOXICITY
240
Q

WOMEN + ART - Are women or men more likely to have poor adherence to ART?

241
Q

WOMEN + ART - which ART is the only one to have licence for use in pregnancy?

A

ZIDOVUDINE

242
Q

WOMEN + ART - how many prospective reports on ART in pregnancy are required before impact on congenital outcomes can be assessed?

243
Q

WOMEN + ART - for which ART is there sufficient reports to suggest no increased risk of congenital abnormality?

A 
abacavir
zidovudine
tenofovir DF
emtricitabine
lamivudine
atazanavir
darunavir
lopinavir
ritonavir
efavirenz
nevirapine
244
Q

What impact does efavirenz have on levonorgestrel?

A

REDUCES levonorgestrel concentrations

245
Q

What is the risk of severe depression or suicidal ideation in people prescribed efavirenz with a past history of mental illness?

246
Q

How does risk of suicidality compare between those on efavirenz vs not on efavirenz?

A

8/1000 vs 4/1000

247
Q

What dose adjustment of EFAVIRENZ is recommended in YOUNG PEOPLE?

A

AVOID standard dose (600mg OD) if:
weight <50kg
AND
history of mental illness

248
Q

What impact does being a YOUNG PERSON have on ART ADHERENCE?

A

reduced adherence

249
Q

What proportion of YOUNG PEOPLE are TRIPLE-CLASS EXPERIENCED?

250
Q

Which tenofovir formulation is preferred in people with osteoporosis or high risk (>20% FRAX) of fragility fracture?

A

Tenofovir ALAFENAMIDE (TAF)

251
Q

In addition to TDF which ART drug class is associated with low bone mineral density?

A

protease inhibitors

252
Q

Is there benefit in switching from PIs if low bone mineral density?

A

NO evidence

253
Q

Which ART has been associated with vitamin D deficiency?

254
Q

Which ART class has been associated with AVASCULAR NECROSIS?

255
Q

What effect does older age have on CD4 cell count?

A

FASTER DECLINE if not on ART

256
Q

What effect does older age have on recovery of CD4 cell count once ART started?

A

LIMITED recovery

257
Q

What is the hypothesis for more limited recovery of CD4 cell count in older age once ART started?

A

THYMIC DYSFUNCTION

lower NADIR CD4 cell count

258
Q

To which ART class is exposure increased with age?

A

Boosted PIs

DipHIV (14 decks)

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