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DipHIV > ART treatment guidelines > Flashcards

ART treatment guidelines Flashcards

1
Q

INSIGHT START 2015 Key findings

A

RCT randomised people with initial CD4>500 to early ART or when <350, 4.1% in deferred arm Vs 1.5% in immediate treatment arm experience a serious illness over 3 years follow up (HIV and non HIV related)

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2
Q

Main trial evidence for starting ART within 2 weeks when presenting with AIDS defining or serious bacterial infection and a CD4<200

A

ACTG 5164 -> fewer AIDS progressions/deaths and improved cost effectiveness when ART commenced within 14 days compared to after completion of acute treatment. No increase in IRIS seen.
(Majority have PCP, TB excluded, very unwell excluded as had to be able to consent)
(most studies favour deferred ART in setting of crypto and TB meningitis)

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3
Q

Poor prognostic factors in pHI indicating ART be started as early as possible

A
  • Neurological involvement
  • Any AIDS defining illness
  • CD4<350
  • PHI diagnosed within 12 weeks of a previous negative test

Data from START, TEMPRANO and HPTN052 showed clinical benefit from starting ART regardless of CD4.
Also reduced transmission risk when VL very high, enhanced probability of immunological recovery to normal levels, limitation of viral reservoir

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4
Q

Evidence for treatment as prevention

A
  • HPTN 052 showed ART yielded 96% reduction in transmission to HIV negative partners and zero transmissions when the parter was undetectable
  • PARTNER, PARTNER2, opposites attract all then confirmed
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5
Q

Conditions to allow monitoring of elite controllers and no treatment, exclude:

A
  • Chronic Hepatitis B, C or HTLV
  • Significant past or present cancer, autoimmune disease or cardiovascular disease
  • Planned immunosuppressive or chemotherapy
  • Pregnancy, planned pregnancy or breastfeeding
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6
Q

Monitoring for viral controllers off ART

A
  • Constitute about 1-5% of all those with HIV 1
  • HIV VL 6-12 monthly
  • CD4 and CD:CD8 ratio at least 6 monthly
  • Clinical assessment 6 monthly for CVD, malignancy, co-morbidities, hepatitis, pregnancy
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7
Q

Rationale for guidelines on viral controllers

A
  • START included patients with low level viraemia and 92 undetectable, subgroup analysis provided data that support immediate ART in setting of low level viraemia although equipoise remains for suppressors.
  • In a French longitudinal study of 302 viral controllers over 14.8 years, 30% clinically progressed
  • Even in controllers, elevated T cell activation can be seen which can be associated with CVD
  • Enrol in trials where possible.
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8
Q

Recommendations for first line?

A

Biktarvy
FTC/3TC + TDF/TAF + Dolutegravir
3TC + Dolutegravir (Dovato)
ABC/3TC/Dolutegravir (Triumeq)

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9
Q

Who cannot start dolutegravir/lamivudine first line?

A

HIV VL>500,000
CD4<200
Hepatitis B co-infection
Transmitted drug resistance
Documented/archived/suspected M184V
HIV related cognitive impairment
Diagnosed in pregnancy
Caution in those with PHI, OI or renal disease

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10
Q

When to do baseline INSTI resistance testing?

A
  • Other major mutations or drug class resistance detected
  • Diagnosis made in pregnancy
  • Likely acquisition from a source with INSTI resistance
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11
Q

What to start if ART naive and evidence TDR?

A
  • TDF/TAF plus 3TC/FTC then either dolutegravir, bictegravir or boosted darunavir
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12
Q

What to start in context of rapid ART initiation?

A

TDF/TAF plus 3TC/FTC then either dolutegravir, bictegravir or boosted Darunavir

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13
Q

What to start in context of very high viral load >500,000

A

TDF/TAF plus 3TC/FTC then either dolutegravir, bictegravir or boosted ritonavir

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14
Q

How long to expect VL to become undetectable?

A

Advise 3-6 months or 1-3 months if INSTI

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15
Q

Monitoring of patients choosing not to start ART

A
  • Counsel as to risk to health and risk onwards transmission
  • Assess capacity
  • Ensure sexual partners are informed and signposted to PrEP
  • Offer regular follow up approx 3 monthly
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16
Q

First line recommended HIV-1 treatment options:

A
  • TDF/FTC or TAF/FTC and dolutegravir
  • TAF/FTC/Bictegravir (Biktarvy)
  • Dolutegravir/Lamivudine (Dovato)
  • Dolutegravir/abacavir/lamivudine (Triumeq)
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17
Q

Recommended as initial treatment in certain clinical situations?

A
  • TAF/TDF + FTC + boosted Darunavir
  • TAF/TDF + FTC/3TC + Doravirine
  • TAF/TDF + FTC/3TC + EFV (e.g. in pregnancy or TB)
  • TAF/TDF + FTC + RAL (only if baseline VL<100,000)
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18
Q

Studies comparing DTG and EFV

A
  • ADVANCE (open label Truvada/Descovy+DTG Vs Atripla -> non inferiority)
  • NAMSAL (DTG based vs 400mg EFV based -> non inferior)
  • SINGLE (Triumeq vs Atripla -> superiority for DTG and fewer discontinuations)
  • Generally DTG showed greater virological success and less adverse event driven discontinuation
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19
Q

Biktarvy studies

A
  • GS1489 (Biktarvy vs ABC/3TC/DTG) -> BMD changes similar in both, greater increases in TC and LDL cholesterol in BIK group)
  • GS1490 (Biktarvy vs TAF/FTC/DTG)
  • Both showed non inferiority for virological success
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20
Q

Studies for once daily dolutegravir/lamivudine

A

GEMINI I AND II
- Treatment naive randomised to DTG/3TC or TDF/FTC/DTG
- Week 4 72% in dual arm and 70% in triple suppressed
- Week 48 91% and 93%
- In those with CD4<200, 68.3% Vs 87.3% in triple suppressed at week 96
- Lower risk drug related AE in DTC/3TC at week 144
- Renal/bone parameters favoured dual
- Mean weight increased in both
- Lipid parameters improved in both although favoured triple

  • Excluded major mutations, hep B, and no one had VL >500,000
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21
Q

Evidence for doravirine:

A

DRIVE-AHEAD:
- TDF/3TC/DOR (Delstrigo) Vs Atripla in treatment naive, non inferior in terms of virological success at week 48 (84.3%<20 vs 80.8% in Atripla), non-inferior regardless of VL>100,000
- Delstrigo had lower rates dizziness + sleep disorders and better lipid parameters
DRIVE-FORWARD:
- 2 NRTIs + DOR Vs 2 NRTIs + DAR/r
- At week 48 non inferior virological success, 88% and 86%, at week 96 favoured DOR (73% vs 66%)
- Rash, neuropsych and lipids better with DOR
DRIVE-SHIFT:
- Switch study from 2 NRTI + EVG/PT/NNRTI Vs Delstrigo
- Non inferiority at week 48
- Lipid reductions better in Delstrigo group

NB: all doravirine studies have compared it to EFZ or DAR/r and shown non-inferiority, have not been compared to INSTIS which have shown superiority to these drugs, hence DOR not recommended unless certain reasons, limited experience with 3TC/ABC and DOR hence not recommended first line

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22
Q

Key raltegravir study informing guidance to be first line only in certain situations

A
  • SPRING-2 was treatment naive 2 NRTI + RAL BD Vs 2 NRTI + DOL
  • DOL was non inferior in terms of virological success at 48 and 96
  • At week 96 if analysed by VL, DTG favoured where VL>100,000
  • Trend towards less virological failure with resistance on DTG (together with known lower genetic barrier for resistance means not recommended unless certain clinical scenarios)
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23
Q

Key darunavir studies informing guidance to start first line only in certain situations

A

FLAMINGO:
- treatment naive, open label so less robust
- 2 NRTI + either DTG or DAR/r
- End point was VL<50 at 48 weeks, DTG was non inferior
- At 96 weeks 80% in DTG Vs 68% in DAR/r with greatest difference in those with high VL at baseline
- In those with VL>100,000, 82% at 96 weeks Vs 52% in DAR/r group
- No difference in virological failure and no resistance in either
- More clinical serious AE in DTG including suicide attempt

ACTG 5257:
- 3 arm study comparing RAL, DAR/r, atazanavir
- All equivalent virological efficacy
- Composite endpoint of efficacy and tolerability RAL>DAR/r>ATZ/r
- RAL tolerability over DAR/r particularly marked in women
- Higher proportion experienced virological failure on DAR/r but individuals on RAL more likely to develop resistance

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24
Q

Why is Dar/r in the first line guidance (in certain circumstances) but not atazanavir/r?

A

ARIA was randomised, open label non inferiority study comparing DTG with ABC/3TC to atazanavir/r
- At week 48 DTG was superior with 82% <20 Vs 71%
- Given the higher rates of virological failure and grade 3 and 4 AEs along with lower virological success, atazanavir/r only in those who need boosted PI but cannot have DAR/r

  • Inferior to RAL in ACTG5257, inferior to TDF/FTC/EVG/c in WAVES, higher emergent CKD in D.A.D
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25
Q

Why Rilpivirine no longer recommended first line?

A
  • Non inferior to EFV with lower rates of toxicity but higher risk of resistance emergence at virological failure, food requirements and interaction with acid reducing agents
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26
Q

Typical resistance patterns on failing NRTI/NNRTI

A
  • 70% are wild type
  • NRTI: M184V (3TC/FTC)
  • NNRTI: K103N/Y181C (EFV), K101/E138K (RPV)
  • INSTI: Q148/N255/Y143 (RAL), R263K (DTG)
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27
Q

What to prescribe when HIV diagnosed in context of suboptimal prep?

A
  • Send resistance but whilst awaited could start:
  • TDF/TAF + FTC/3TC + DTG/DARr/c/BIK
  • (Despite M184V being common still effective)
  • (same as what to start in context of rapid ART initiation or very high viral load)
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28
Q

Transmitted drug resistance prevalence in UK baseline tests 2016

A
  • 9.6% had at least one mutation
  • 4% NRTI, 4% NNRTI, and PI 2%
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29
Q

If previous NRTI resistance mutations, what should you not switch a boosted PI regimen to? (in the context of switch in virological suppression)

A
  • NNRTI or first generation INSTI
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30
Q

Recommendations for choice of ART for suppressed switch or maintenance:

A
  • NNRTI 3-drug: DOR or RPV maintenance or switch, NVP/EFZ maintenance only
  • INSTI 3-drug: DTG,BIC,EVG/c,RAL
  • PI based 3-drug: atazanavir/r/v, or DAR/r/c, LOP/r
  • DTG/3TC
  • DTG/RPV
  • CAB/RPV
  • RAL/DAR/r/c
  • 3TC or FTC with PI
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31
Q

When would guidelines recommend you could use DTG/RPV?

A
  • Studied only in suppressed switch, high risk of NNRTI resistance at VF
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32
Q

When would guidelines recommend you could use RAL with boosted darunavir?

A

Suppressed switch, underperformed at high VL>100,000 and CD4<200 when used first line

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33
Q

When would guidelines recommend you could start DTG with boosted Darunavir?

A

Studied only in suppressed switch

34
Q

When would guidelines recommend you could start 3TC or FTC with a boosted PI? (Ie 2 drug regimen)

A

Suppressed switch only, in absence of known or suspected M184V/I
Several studies demonstrate non inferiority of lamivudine with a boosted PI (ATLAS-M demonstrated switch to lamivudine plus atazanavir/r was superior to continuing TDF/FTC plus atazanavir/r in people with viral suppression and no NRTI resistance)

35
Q

Facts about M184V

A
  • Emerges rapidly in those on non-suppressive therapy with FTC/3TC and is the most common NRTI mutation seen with VF
  • Alone confers >200 fold resistance to FTC/3TC
  • Continues to have partial activity
  • It impairs viral fitness
  • Worsen susceptibility to Abacavir when present with TAMS (no effect alone)
  • Improves susceptibility to Tenofovir, AZT and stavudine
36
Q

K65R key facts

A
  • Occurs more rapidly in HIV-1 subtype C
  • After M184V, is the most common NRTI associated resistance mutation to develop in patients receiving TDF regimen
  • K65R is selected by TDF/TAF, ABC and rarely 3TC
  • K65R reduces TDF/TAF and ABC susceptibility around 2 fold, reduces 3TC/FTC susceptibility 5-10 fold
  • Increases AZT susceptibility except when in combination with Q151M
  • K65R rarely occurs in combination with TAMS because they exhibit bidirectional antagonism
37
Q

What did SINGLE study show?

A

EFV was inferior to DTG with higher suicidality rates, more adverse events and discontinuations

38
Q

Most common transmitted PI resistance

A

L90M
M46L

39
Q

If people have experienced virological failure, NRTI choice should be guided by resistance testing (or suspected resistance), therefore which backbone and why?

A

TDF based backbone when M184V seen/suspected as it reduces abacavir sensitivity and leads to tenofovir hypersusceptibility

40
Q

TDF to TAF effect on lipids

A

Increases in triglycerides and total, LDL and HDL
Minimal change in total/HDL cholesterol level
Associated with average weight gain of 1.6kg at week 48

41
Q

SWITCH MRK study
ODIS
SPIRAL

A
  • Multi centre, double blind, phase 3 RCT
  • Switching from LOP/r to RAL 400mg BD
  • Non inferiority was NOT shown, lower rates of HIV suppression were seen especially in patents who had a prior history of virological failure
  • ODIS showed similar to SWITCHMARK, SPIRAL was contrasting and showed non inferiority between boosted PI and RAL
42
Q

DAWNING

A
  • Treatment experienced adults failing first line ART (NNRTI and 2NRTI)
  • Switched to either LOP/r or DTG
  • DOL superior virological suppression even in the presence of NRTI resistance mutations (M184V, K65R)
  • Median time to suppression much better in DTG group
  • Showing that DTG (with 2NRTI) effective even with NRTI resistance, unlike RAL
43
Q

Studies providing evidence against DTG monotherapy

A

MONCAY
DOMONO
- less virological suppression and more INSTI resistance

44
Q

Studies supporting DTG/3TC switch

A

TANGO
- Open label, randomised to remain on TAF based therapy or switch to DTG/3TC
- End point virological failure - non inferiority shown at 48 weeks
- No resistance, no increased failure in presence of pro-viral M184V

ASPIRE
- Switching from any 3 drug regimen to DTG/3TC
- End point virological failure, non inferiority shown at week 48

45
Q

who can’t do suppressed switch to DTG/3TC

A

Don’t give if:
- Pregnant
- Hep B non immune and at risk
- Hep B co-infection
- Previous INSTI or 3TC resistance
- Previous failure on an INSTI
- Evidence largely from TANGO
- Some improvement in lipid seen if switching from boosted regimen

46
Q

Who can’t have DTG/Rilpiverine (Juluca) in setting of suppressed switch

A

Not if:
- History of previously virological failure or resistance to any NNRTI or INSTI
- Those with Hep B/non immune and at risk
- Evidence largely from SWORD (Juluca Vs current ART): non inferior in terms of VL<50 at week 48, neutral lipids, bone better dual, no clear evidence for safety or efficacy benefits
- No treatment naive DOL/RPV studies so only recommended as a switch

47
Q

Boosted PI and lamivudine

A

Generally no recommended due to PI side effects and DDI
However, could be considered in switch situation if absence of Hep V, no previous virological failure or lamivudine resistance

48
Q

Who can have two drug injectable regimen with CAB/RPV?

A
  • Have significant need for injectable ART
  • VL<50 for at least 6 months
  • No known or suspected NNRTI or INSTI resistance
  • No history of virological failure or unplanned treatment interruption on NNRTI or INSTI
  • No history of INSTI monotherapy
  • Can commit to 2 monthly injections
  • Accept the risk of VF despite complete adherence (1 in 70 a year at year 1, 1 in 60 at year 2)
  • Only one of: baseline RPV polymorphisms, BMI>30 or A1/6 subtype if baseline resistance unavailable
  • Do not need tenofovir containing regimen for treatment or prevention Hep B

Can be continued in people:
- Received it as part of a trial
- Are on for compassionate or named patient progamme

All will need:
- 2 monthly VL
- Prompt recall for testing/resistance if rebound

49
Q

LATTE studies

A
  • phase 2b
  • LATTE 1: ART randomised to different doses PO CAB or EFV with dual NRTI, if suppressed then received a 2 drug regimen of their randomly allocated drug/dose with rilpivirine 25mg
  • As a 2 drug maintenance therapy, CAB+RPV was non inferior to EFV + 2NRTI
  • Combined efficacy and safety results meant CAB 30mg chosen
50
Q

ATLAS study

A
  • IM CAB+RPV 4 weekly was non inferior to daily oral ART at week 48 (in terms of virological success and failure)
  • VF in each arm around 1%, however the 3/300 patients in IM group developed resistance at failure (2 NNRTI, 1 INSTI)
51
Q

ATLAS 2M

A
  • Compared LA CAB/RPV 1 monthly or 2 monthly, was non inferior in terms of efficacy
  • NB no direct comparisons of 2 month to oral
52
Q

FLAIR

A
  • IM CAB/RPV every 4 weeks non inferior to PO triumeq at week 48 in terms of virological success and failure
  • Around 300 in each arm, of which 3 per group developed virological failure
  • None of the 3 in triumeq group developed resistance, however all 3 in LA arm did (both NNRTI and INSTI), all were subtype A1
53
Q

Counselling someone wanting to start IM CAB/RPV

A
  • Not suitable if ever had treatment interruption, virological failure or resistance
  • Will have to take oral lead in for 4 weeks, will then have 2 injections 1 month apart then injections 2 monthly
  • Excellent adherence is critical, +/- 7 day window for early/lat administration, oral bridging would be in emergency
  • 2x deep gluteal injection
  • In trials, even with perfect adherence 1 in 70 on 2 monthly injections have viral rebound at 1 year and 1 in 60 at 2 years with most of these having resistance
  • NOT recommended in pregnancy as not tested (however if already on it and become pregnancy can remain on it)
54
Q

Discussion points to help with adherence:

A
  • Alarm clock
  • Record medicine taking
  • Pill box with days of week
  • Simplify pills
  • Link to activity
  • If stigma offer alternative reasons for medication e.g. contraception
  • Alternative packaging
  • Screen and treat depression
  • Screen for etoh and drug use
  • Ask about socioeconomic factors and signpost to support
55
Q

If stopping ART completely and regimen contains EFV/NVP/ETV with NRTI backbone, what to do?

A
  • Replace all drugs with DAR/r for 4 weeks
56
Q

What to when switching from NNRTI to other drugs

A
  • Etravirine is a potent inducer, EFV moderate, NVP weak
  • If switching from EFV or NVP in context of viral suppression, a direct switch without dose adjustment is fine (if detectable a switch to boosted PI preferable to within class switch)
  • If switching from etravirine to DTG, increase DTG to 50mg BD for 2 weeks (as you cannot easily dose adjust when switching to EVG/DOR/BIC advice is to only do it when suppressed and to check VL)
  • If switching from EFV to maraviroc, increase to 600mg BD for 7 days
57
Q

Oral lead in when switching from NNRTI to CAB/RPV

A
  • With etravirine/EFV give normal dose 30mg CAB but double dose RPV 50mg for 2 weeks then 2 weeks standard dosing (30mg + 25mg)
    OR standard dose CAB/RPV PO with additional 2NRTI cover
  • With NVP 4 weeks standard dosing is fine
58
Q

Definition of incomplete virological response

A
  • VL>200 in two consecutive tests after 24 weeks without ever achieving undetectable
59
Q

Definition of virological failure and virological rebound

A

Virological failure: incomplete virological response after starting treatment or evidence of viral rebound to >200
Virological rebound: 2 confirmed tests that are not below the lower limit of detection

60
Q

Management of a blip

A
  • Adherence, DDI search and repeat test 2-6 weeks
  • Reassure not usually linked to VF or resistance when just a one off
  • Some may be due to assay variation and lab processing artefacts
  • If LLV then at higher risk of VF
61
Q

Management of low level viraemia

A
  • Resistance testing
  • Ensure high genetic barrier regimen used and a 3 drug regimen
  • LLV is seen in around 8% of people at it is associated with risk of VF and resistance
  • Many people with LLV in studies have low drug levels (ie. it’s an adherence issues)
  • LLV is associated with immune activation
  • If the LLV is <50, no changes required
62
Q

Management of virological failure (VL>200)

A
  • Rapid re-test +/- resistance
  • 70% in UK have no major resistance
  • Review adherence, drug exposure, tolerability, DDI, food interaction, significant renal/liver, mental health, drug dependency
  • Resistance testing whilst on failing therapy or within 2-4 weeks or stopping
  • Review past ART and resistance tests for archived resistance
  • Tropism if considering Maraviroc
  • Intensification with single ART not recommended
  • Once VF confirmed, and preferably once resistance test available, change as soon as possible.
  • Don’t ever forget about hep B
63
Q

Regimen if multi class resistance

A
  • MDT advice
  • Avoid treatment interruption
  • Include at least 2 if not 3 fully active agents including boosted PI and 1 agent with a novel mechanism
64
Q

Mechanism of action of:
- Fostemsavir
- Ibalizumab
- Lenacapavir
- T20

A

Fostemsavir: targets glycoprotein 120
Ibalizumab: monoclonal targeting CD4
Lenacapavir: capsid inhibitor
T20/Enfuratide: Fusion inhibitor

65
Q

What to do if virological failure and no resistance found?

A
  • Adherence etc.
  • Probably a good idea to ensure a 2nd gen INSTI or darunavir/r
  • If VF on NNRTI, likely to be NNRTI resistance +/- NRTI resistance
  • Repeat test in 4 weeks
66
Q

What to do if first line treatment failure with NNRTI resistance?

A
  • UP to 2/3rds of those failing NNRTI/NRTI treatment will have NNRTI RAMs and half NRTI RAMs
  • Evidence supports doing one of 3 things:
  • Switch to 2NRTI + DTG (DAWNING, NADIA, VISEND)
  • Switch to 2NRTI plus boosted PI (NADIA)
  • Switch to boosted PI plus INSTI
67
Q

NADIA trial

A
  • 2 by 2 factorial open label study in those failing first line therapy
  • Randomised to receive DTG or DAR/r, and AZT or TDF and all have 3TC
  • Non inferiority shown in terms of virological suppression
  • Even when expected TDF resistant mutations, TDF did just as well as AZT
  • Similar virological rebound (6%) in both but in the DTG group 4 developed resistance, none in the DAR group
68
Q

What to do if first line treatment failure on 2NRTI and boosted PI?

A
  • Less than 1% will have PI mutations, 10-20% have NRTI mutations and 75% wildtype
  • Adherence etc and repeat 4 weeks, if still VF do resistance
  • Limited data about what to switch to
  • Could switch to different PI, 2nd gen INSTI or both
  • Switching to NNRTI or maraviroc with 2 active NRTI is an option but not recommended if historical or existing NRTI mutations or previous failure on NRTI regimen
69
Q

What to do if first line treatment failure with 1st and 2nd generation based INSTI

A
  • In studies on VF in RAL or EVG up to 50% were found to have integrase resistance, but it is very rare in setting of DTG or BIC
  • Boosted PI may be a good option
  • VIKING 3 showed that those with integrase mutations after failing RAL/EVG on switch to DTG over 50% achieved suppression
  • If considering switching to DTG after first line failure with RAL/EVG resistance, do BD DTG (no data on BIC)
70
Q

For those with multi-class virological failure with or without extensive drug resistance

A
  • MDT
  • Review all past and current resistance tests and treatment history
  • With extensive drug resistance switch to new ART regimen with at least 2 and preferably 3 fully active agents
  • if extensive resistance consider novel agents
  • Intensive adherence support
  • Can recycle NRTI even in presence of predicted resistance
  • Where feasible, including DAR/r probably advisable
71
Q

Which studies support use of NRTI containing regimen in 2nd line treatment for virological failure even in presence of extensive NRTI resistance?

A

NADIA, DAWNING, Earnest trial group study

(M184V enhances in vitro TDF susceptibility, also theorised that there may be clinical benefit due to the replication deficit it provides)

72
Q

Specific guidance for adolescents:

A
  • Avoid TDF in <25
  • See in specialised services until age 23-25
  • ART should be OD regimen with low pill burden and high genetic barrier based on 2nd gen INSTI plus 2XNRTI
  • Need multi agency support and consideration of injectables
  • Mortality of those with VT are 10x higher than in age matched controls
  • FRAX scores only validated from 40 years, so do a DEXA if concerned e.g. if prolonged viraemia, reduced mobility, abnormal BMI, growth stunting, steroid use
73
Q

Bone disease specific guidance

A
  • Do not give TDF
  • High risk of fragility fracture if FRAX>10%
  • Several studies have shown reduced BMD with TDF and also showed than when switched BMD improved
  • No difference in incidence of fractures yet shown
  • PIs can cause avascular necrosis
74
Q

Cardiovascular and metabolic disease considerations

A

Elevated CVD risk:
- Established atheroscelorotic CVD
- DM1>40 yrs
- eGFR<60 +/- albuminaemia
- Familial hyperchol
- QRISK>10%

Avoid abacavir, if needed boosted PI atazanavir may have advantages over DAR

75
Q

Which ART are associated with dyslipidaemia

A
  • Boosted PIS
  • EVG/c
  • EFV
  • Switch from TDF to TAF may see slight deterioration in lipids although preservation of the total/HDL ratio
76
Q

Weight gain and ART

A
  • TAF more compared to TDF or ABC, most marked in Black women, TDF->TAF associated with approx 2kg at 1 year (in part due to loss of weight restriction)
  • INSTI (compared to NNRTI or boosted PI, worse with BIC/DTG)
  • If Rx naive worth discussing ‘return to health’
  • Can advise average weight gain in population is 0.5kg/year
  • Offer lifestyle advise, dietician, signpost to services, advise stopping the drug may not lead to weight loss
77
Q

CKD considerations for ART

A
  • If PI then DAR if eGFR<60
  • No TDF if eGFR<60
  • No TAF if eGFR<30
78
Q

ART with nephrotoxic potential

A
  • TDF (eGFR decline, CKD proteinuria, Fanconi)
  • Atazanavir (stones, tubulointerstitial nephritis, CKD)
  • LOP/r (CKD)
79
Q

ART and ESRD:

A
  • e.g. if eGFR 15-29 TAF results in 5-6 fold higher tenofovir levels compared to normal, could consider low dose TAF10mg/200mg with careful monitoring of kidneys (e.g. if needed for HBV)
  • 3TC/FTC dose adjusted eGFR<30
  • All NNRTI except ABC renally cleared
  • For transplant no PI/booster, no TDF, ideally no TAF, DTG/3TC or DTG/RPV good options
80
Q

ART and neuro considerations

A
  • Don’t use EFV with cognitive impairment
  • INSTIs can cause insomnia/anxiety, no evidence cognitive impairment
  • Avoid dual therapy in HIV associated cognitive disorders

DipHIV (8 decks)

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