If the Drugs Are Working, Why Switch HIV Treatment in People Who Are Virologically Suppressed?

Sharon Walmsley, MD, and Mario Cascio, discuss HIV in this CME activity titled "If the Drugs Are Working, Why Switch HIV Treatment in People Who Are Virologically Suppressed?" For the full presentation, please visit us at www.peervoice.com/VZX870.

1. PeerVoice

If the Drugs Are Working, Why Switch HIV Treatment in People
Who Are Virologically Suppressed?

Learning Objectives
Explain the rationale for switching antiretroviral therapy (ART) regimens in people
with virologically suppressed HIV
Assess the clinical and patient-reported outcomes (PRO) data for HIV switch
regimens for people with virologically suppressed HIV
Based on clinical trial populations, evaluate eligibility criteria of people with
virologically suppressed HIV for an ART switch

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2. PeerVoice

Part 1 of 2: Clinician and Individual Perspectives on Switching HIV ART:
When Treatment Is Working, Why Switch?

k es

Sharon Walmsley, MD Mario Cascio

Professor of Medicine Board Member and Advocate
University of Toronto NPS Italia APS

Director, Immunodeficiency Clinic & HIV Clinical Research Milano, Italy

University Health Network

Toronto, Ontario, Canada

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3. PeerVoice

Sharon Walmsley, MD, has a financial interest/relationship or affiliation in the form of:
Grant/Research Support from Gilead Sciences, Inc.; GSK plc.; Janssen Inc.; Merck KGaA;
and ViiV Healthcare ULC.

Advisory Board or Panel for Gilead Sciences, Inc.; Merck KGaA; and ViiV Healthcare ULC.

Mario Cascio has a financial interest/relationship or affiliation in the form of:
Consultant for ViiV Healthcare ULC.

Speakers Bureau participant with Gilead Sciences, Inc.

These relationships have ended.

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4. PeerVoice

ART Switch: Challenges

A Maintaining virological suppression
? Lack of certainty that the switch will add any benefit or will fix/prevent the problem
:

FI

Sa

I, 29] Resistance Adherence
Ko

fects and tolerability

( € ] Drug-drug interactions Side

Access and affordability

©
& Psychological and emotion:

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5. PeerVoice

ART Switch: Potential Harms

Cardinal principle of regimen switching
Maintain viral suppression without jeopardising future options

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6. PeerVoice

Patient-Clinician Collaboration: Joint Decision-Making

Y
@
©

Understanding the patient's values, preferences, and goals

Holistic approach to patient care

Ensure care is collaborative, accessible, and aligned with patient goals

Propose treatment change to receptive patients

|

Suggest clinical trials when appropriate and consider latest data

Recognise barriers unique to marginalised populations

SS

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Abbreviations and References

ART Switch: Challenges

Reference(s): Sharon Walmsley, MD. PeerVoice interview; July 2024.
ART Switch: Potential Harms

Reference(s): Sharon Walmsley, MD. PeerVoice interview; July 2024.

Patient-Clinician Collaboration: Joint Decision-Making

Reference(s): Sharon Walmsley, MD, and Mario Cascio. PeerV

e interview; July 2024.

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8. PeerVoice

Part 2 of 2: Switch Options for People With Virologically Suppressed HIV:
The Current and Emerging Treatment Landscape

4 LS

Sharon Walmsley, MD Mario Cascio

Professor of Medicine Board Member and Advocate
University of Toronto NPS Italia APS

Director, Immunodeficiency Clinic & HIV Clinical Research Milano, Italy

University Health Network

Toronto, Ontario, Canada

Copyright © 2010-2024, PeerVoice

9. PeerVoice

Sharon Walmsley, MD, has a financial interest/relationship or affiliation in the form of:
Grant/Research Support from Gilead Sciences, Inc.; GSK plc.; Janssen Inc.; Merck KGaA;
and ViiV Healthcare ULC.

Advisory Board or Panel for Gilead Sciences, Inc.; Merck KGaA; and ViiV Healthcare ULC.

Mario Cascio has a financial interest/relationship or affiliation in the form of:
Consultant for ViiV Healthcare ULC.

Speakers Bureau participant with Gilead Sciences, Inc.

These relationships have ended.

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10. PeerVoice

Principles for Successful Regimen Switching

Review ART history:
+ Virologic suppression, resistance test results, and past adverse events

+ If resistance data are unavailable, resistance may often be inferred by
treatment history

+ Consult with an HIV specialist for patients with a history of resistance to
21 drug classes

During the first 3 months after a regimen switch:

+ More intensive monitoring of tolerability, viral suppression, adherence,
and laboratory changes

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Principles for Successful Regimen Switching (Cont'd)

| }——

Switching from an agent with a high barrier to resistance to one with a lower
barrier to resistance may result in virologic failure

Correcting a laboratory abnormality
Achieving some other benefit

Many switch studies do not include patient-reported outcomes (PRO)

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12. PeerVoice

ART Switch: Summary of Efficacy and Safety Data

(Trial)

Bictegravir,
emtricitabine, and
tenofovir alafenamide
(GS-US-380-4030)!

Frequency
and Route

Oral;
once daily

Efficacy Overview

‘Switching to B/F/TAF was
noninferior to DTG + F/TAF
at week 48

Safety Overview

TRAES: 14% with B/F/TAF vs 10% with DTG+F/TAF
Most common TRAEs were diarrhoea and
headache (both: 1% with B/F/TAF
vs 2% with DTG+F/TAF)

Cabotegravir and
rilpivirine
(ATLAS and FLAIR)?

IM;
once every 1
or 2 months

‘Switching to CAB/RPV every 4
weeks was noninferior to oral
ART through week 96
PRO: 91% preferred CAB and
RPV at week 48

SAEs: 6% with CAB/RPV vs 4% with
DTG+ABC+3TC oral therapy
Most common AE: Injection-site reactions
(«1% were grade 23; 88% resolved within 7 days)

Dolutegravir and
lamivudine
(SALSA)?

Oral;
once daily

Switching to DTG/3TC was
noninferior to continuing CAR
for maintaining virologic
suppression at week 48

TRAES more frequent with DTG/3TC (20%) vs
CAR (6%) through week 48 but comparable
post-week 24 (5% vs 2%)

AEs 25% with DTG/3TC: Weight increase (8%),
headache (7%), COVID-19 (6%), back pain (6%),
insomnia (6%), and dizziness (5%)

Doravirine, lamivudine,
and tenofovir disoproxil
fumarate
(ORIVE-SHIFT)*

Oral;
‘once daily

Switching to DOR/3TC/TDF
was noninferior to BL
regimen at week 24

TRAE: 19.5% of the DOR/3TC/TDF ISG and 2.2% of
the BL DSG; none occurred in 22% of either group
Most common AEs were
nasopharyngitis and headache

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Emerging ART Regimens

Frequency and

Regi Poel MoA Data Overview
IV; 2 doses in
3BNCII7 and the first month | Monoclonal | Phase 1: Viral suppression in treatment-naive
10-1074! and once a antibodies patients (Week 43)
month after
ts Fun Phase 2b: Viral suppression maintained
Goal ns das NRTTI (Week 96) and well tolerated regardless of dose
Y Phase 3: Ongoing
Islatravir/ Oral; Phase 2 trial: 94% maintained suppression
lenacapavirt once a week NRTTi after switch (Week 24)
Teropavimab and ve ola Broadly Phase Ib: 8 out of 10 patients maintained
zinlirvimab plus evaluationat | neutralising | virological suppression at week 26, including
lenacapavirs e Weake antibodies 6 of 6 in the LEN+TAB+ZAB 30 mg/kg arm

Note: Not a complete list of ART regimens under investigation.

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Abbreviations and References

Principles for Successful Regimen Switching
Abbreviation(s): ART: antiretroviral therapy.

Reference(s): Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the Use of Antiretroviral
Agents in Adults and Adolescents with HIV. Department of Health and Human Services.
https://clinicalinfo.hiv.gov/sites/default/files/guidelines/documents/AdultandAdolescentGL pdf. Accessed 9 July 2024.

Principles for Successful Regimen Switching (Cont'd)

Reference(s): Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the Use of Antiretroviral
Agents in Adults and Adolescents with HIV. Department of Health and Human Services.
https://clinicalinfo.hiv.gov/sites/default/files/guidelines/documents/AdultandAdolescentGL pdf. Accessed 9 July 2024.

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Abbreviations and References (Cont'd)

ART Switch: Summary of Efficacy and Safety Data

Abbreviation(s): 3TC: lamivudine; AE: adverse event; B: bictegravir; BL: baseline; CAB: cabotegravir; CAR: current
antiretroviral regimen; DOR: doravirine; DSG: delayed switch group; DTG: dolutegravir; F: emtricitabine;
IM: intramuscular; ISG: immediate switch group; PRO: patient-reported outcome; RPV: rilpivirine; SAE: serious adverse
event; TAF: tenofovir alafenamide; TDF: tenofovir disoproxil fumarate; TRAE: treatment-related adverse event.
Reference(s): 1. Sax PE et al. Clin Infect Dis. 202173:2485-e493,

2. Orkin C et al. N Engl J Med. 2020:382:124-1135.

3. Libre JM et al. Clin Infect Dis. 2023;76:720-729.

4. Johnson M et al. J Acquir Immune Defic Syndr. 2019:81:463-472.

Emerging ART Regimens

Abbreviation(s): i: inhibitor; IV: intravenous; LEN: lenacapavir; MoA: mechanism of action; NRTT: nucleoside reverse
transcriptase translocation; TAB: teropavimab; TBD: to be determined; ZAB: zinlirvimab.

Reference(s): 1. Sneller MC et al. Nature. 2022;606:375-381.

2. Molina JM et al. 2023 Conference on Retroviruses and Opportunistic Infections (CRO! 2023); Abstract 196.

3. Molina JM et al. Lancet HIV. 2024. doi:https://doi.org/10.1016/52352-3018(24)00031-6.

4. Colson A et al. 2024 Conference on Retroviruses and Opportunistic Infections (CRO! 2024); Abstract 208.

5. Eron JJ et al. CRO! 2024; Abstract 120.

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