Long acting Injectable

HIV Medication and

ILANA Study
Dr Hamzah Farooq
Clinical Research Fellow
Specialist Registrar in Infectious Diseases & Virology
SHARE Collaborative
Queen Mary University of London

©2021 SHARE - Research for Health Equity 1

Three-Drug Regimens (3DR) and Two-Drug Regimens (2DR)

• Most licensed antiretrovirals target one of three viral enzymes:

1. Reverse transcriptase: nucleoside and nonnucleoside reverse transcriptase
inhibitors (NRTI and NNRTI, respectively).
2. Integrase: integrase strand transfer inhibitors (INSTI).
3. Protease: protease inhibitors (PI)

• In the mid-1990s protease inhibitor, swiftly followed by NNRTI, permitted durable viral
suppression by combining two NRTI and a third drug; this ‘recipe’ has remained
standard of care since, allowing incredible achievements including life expectancy
normalization
• Most three-drug regimens (3DR) include ABC or TDF, but concerns around their long-
term toxicities are a driver to explore 2DR.

ILANA Implementing Long-Acting Novel Antiretrovirals

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Three-Drug Regimens (3DR) and Two-Drug Regimens (2DR)

• Multiple studies have recently showed non-inferiority of 2DR vs 3DR:

• GEMINI I & GEMINI II (DTG/3TC)
• TANGO (DTG/3TC)
• SWORD I & SWORD II (DTG/RPV)
• Dualis (DTG/DRV/r)

• Due to above and other studies, European (EACS), British (BHIVA) and other
organisations globally recommend 2DR regimens in cases:
• In persons with suppression of HIV-VL < 50 copies/mL for the past 6 months
• these dual therapy strategies should only be given if there is
a) No historical resistance and
b) HBV immunity or if non-immune concomitant HBV Vaccination

ILANA Implementing Long-Acting Novel Antiretrovirals

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Injectable ARV Medication

• Multiple trials have shown that injectable ARV medication is effective and safe:

ILANA Implementing Long-Acting Novel Antiretrovirals

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 Trial Phase n Arms
 LATTE-2  IIb  286  •LAI CAB (400 mg) + LAI RPV (600 mg) q4w
•LAI CAB (600 mg) + LAI RPV (900 mg) q8w
•CAB (30 mg) + ABC/3TC (600/300 mg) q24h
 FLAIR  III  566  •LAI CAB (400 mg) + LAI RPV (600 mg) q4w
•DTG/ABC/3TC (50/600/300 mg) q24h
 ATLAS  III  616  •LAI CAB (400 mg) + LAI RPV (600 mg) q4w
•2 NRTIs + 1 INSTI, NNRTI or boosted PI or unboosted
ATV
Results
•At Week 96, viral suppression:
• q4w: 87% (100 of 115 patients)
• q8w: 94% (108 of 115 patients)
• oral: 84% (47 of 56 patients)
•At Week 48, viral suppression:
• LAI: 93.6% (265 of 283 patients)
• oral: 93.3% (264 of 283 patients)
•At Week 48, viral suppression:
• LAI: 92.5% (285 of 308 patients)
• oral: 95.5% (294 of 308 patients)

ATLAS-2M  IIIb  1045  •LAI CAB (400 mg) + LAI RPV (600 mg) q4w •At Week 48, viral suppression:
•LAI CAB (600 mg) + LAI RPV (900 mg) q8w • q4w: 93% (489 of 523 patients)
• q8w: 94% (492 of 522 patients)
PrEP 
  IIb/III  4566  •LAI CAB (600 mg) q8w •LAI CAB: Incidence rate 0.41%
HPTN083a  •TDF/FTC (300/200 mg) q24h •(13 HIV infections)
(Ongoing-   •TDF/FTC: Incidence rate 1.22%
study) •(39 HIV infections)
 
  III  3224  •LAI CAB (600 mg) q8w •LAI CAB: Incidence rate 0.21%
HPTN084a  •TDF/FTC (300/200 mg) q24h •(4 HIV infections)
Ongoing-   •TDF/FTC: Incidence rate 1.79% (34 HIV infections)
study)  

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 ATLAS-2M 152 Weeks: Safety and Treatment Satisfaction 1
/ Safety profiles of Q8W and Q4W dosing at Week 152 are similar and consistent with previous analyses
/ No new safety signals were identified since Week 48
/ Since Week 96, excluding ISRs, there were 2 participants with drug-related AEs leading to withdrawal‡
/ ISRs were mostly Grade 1-2 (99%), short-lived (median duration, 3 days), with few discontinuations (2%) due to
injection-related reasons through 152 weeks (3 additional participants since Week 96)

100
Overall ISRs
Participants with ISRs* (%)

CAB + RPV LA Q8W Grade 1 or Grade 2

CAB + RPV LA Q4W Grade 1 or Grade 2
80 Grade 3†

60

40

20

0
D1 W4 W8 W12 W16 W20 W24 W28 W32 W36 W40 W44 W48 W52 W56 W60 W64 W68 W72 W76 W80 W84 W88 W92 W96 W100 W104 W108 W112 W116 W120 W124 W128 W132 W136 W140 W144 W148 W152

Participants Q8W 194 322 514 NA 511 NA 502 NA 496 NA 495 NA 493 NA 487 NA 485 NA 481 NA 482 NA 480 NA 473 NA 462 NA 456 NA 458 NA 460 NA 459 NA 456 NA 456
at visit Q4W 196 515 515 513 508 502 503 502 499 492 491 490 488 483 480 480 477 477 476 478 475 475 475 470 468 464 459 450 451 450 449 453 455 456 454 449 449 446 448

CAB + RPV LA administered every 2 months demonstrated durable, non-inferior efficacy,

comparable safety outcomes, and significantly higher participant treatment satisfaction
to monthly dosing over 152 weeks of treatment

*AE grade is the maximum grade reported by the participant at each visit. †There were no Grade 4 or 5 ISRs.
‡
Lipoatrophy and pyrexia (both Q4W). No drug-related serious AEs were reported. §In participants without prior CAB exposure. 1. Overton et al. CROI 2022; Virtual. Poster 479
‖
Adjusted for baseline score, sex at birth, age (<50, ≥50 years), race (White, non-White), and third agent class (INI, PI, NNRTI). 2. Data on file, ViiV Healthcare.
ATLAS-2M 152 Weeks: Safety and Treatment Satisfaction 1
/ HIV treatment satisfaction questionnaire§ total mean scores significantly improved‖ from baseline (Q8W, 57.73; Q4W, 56.72) to Week 152 for
both treatment groups
/ The mean change‖ from baseline significantly favored Q8W dosing at all 3 timepoints

Adjusted‖ mean (95% CI) change from baseline in total HIVTSQs score2
Q8W – Q4W
5.07 (4.36, 5.778) 1.07 (0.07, 2.07)
Week 24 p=0.036
4.00 (3.30, 4.70)

4.86 (4.02, 5.69) 1.73 (0.56, 2.91)

Week 48 p=0.004
3.12 (2.29, 3.95)
4.98 (4.15, 5.82) 1.75 (0.57, 2.93)
Week 152 p=0.004
3.23 (2.40, 4.06)

0 1 2 3 4 5 6
Q8W (n=319) Q4W (n=323)

CAB + RPV LA administered every 2 months demonstrated durable, non-inferior efficacy,

comparable safety outcomes, and significantly higher participant treatment satisfaction
to monthly dosing over 152 weeks of treatment

*AE grade is the maximum grade reported by the participant at each visit. †There were no Grade 4 or 5 ISRs.
‡
Lipoatrophy and pyrexia (both Q4W). No drug-related serious AEs were reported. §In participants without prior CAB exposure. 1. Overton et al. CROI 2022; Virtual. Poster 479
‖
Adjusted for baseline score, sex at birth, age (<50, ≥50 years), race (White, non-White), and third agent class (INI, PI, NNRTI). 2. Data on file, ViiV Healthcare.
 The ILANA Study:
Implementing Long-Acting
Novel Antiretrovirals

Chief Investigator: Professor Chloe Orkin

Professor in HIV Medicine

Queen Mary University of London

8
©2021 SHARE - Research for Health Equity
 Background- about CAB/RPV

• LA therapy beneficial elsewhere in Medicine

• Many studies have demonstrated demand and interest in long-acting therapies in PWH

• Long-acting CAB and RPV LA is effective and safe (three large phase III clinical trials).

• Participants on CAB and RPV LA overwhelmingly preferred it to daily oral therapy.

• This treatment makes it possible to remove the burden of daily oral therapy

• Opens up the possibility of achieving viral suppression for those who, for a myriad of complex
reasons, can’t or won’t take oral therapy.

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Background

• EMEA approval December 17th 2020 - 2 monthly CAB/RPV

• MHRA approval too.
• NICE approval 18 November 2021
• British HIV Association Guidelines in 2022 – focus on those who need it most in first
instance
Who is CAB/RPV for:
• maintenance treatment of adults with HIV-1 with undetectable VL on ART
• without hepatitis B co-infection
• in whom there is no known or suspected resistance to CAB and RPV LA (INSTI or
NNRTI).

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Background- where will the trial take place?

• Six large clinic sites both in London and outside of London.

Individual Site Principal Investigators

Barts Health NHS Trust: Dr Vanessa Apea
Brighton and Sussex University Hospitals NHS Trust: Dr Amanda Clarke
Chelsea and Westminster Hospital NHS Foundation Trust: Dr Ruth Byrne
Guy's and St Thomas' NHS Foundation Trust: Dr Julie Fox
Royal Free London NHS Foundation Trust: Dr Tristan Barber
Royal Liverpool University Hospital: Dr Emily Clarke

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Background- what is the intervention

• All PWH participants will be receiving CAB and RPV LA as part of their routine
care, regardless of the study.
• It is a pragmatic real-world implementation trial
• This study explores implementation of a standard of care treatment in two
delivery sites.
• Each site will identify the most workable option to deliver of CAB and RPV LA
according in the community setting within their region or borough.
• Any patient who does not wish to participate in this study, will still receive the
treatment if they wish as part of their routine care.

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Objectives
• Primary objective: 
• To evaluate the feasibility of long-acting Cabotegravir and Rilpivirine (CAB and RPV LA)
administration at NHS HIV clinics and community settings for people with HIV (PWH) who plan to
receive the treatment as part of their routine clinical care.
• Secondary objectives:
• To evaluate the feasibility of CAB and RPV LA administration at six HIV clinics in England and
community-based settings for HIV care providers, nurses and community site staff
• To evaluate the acceptability of CAB and RPV LA for patients, nurses, and HIV care providers
• To evaluate the feasibility and acceptability of CAB and RPV LA at pre-specified region-specific
community-based sites
• To describe adherence to the dosing window
• To evaluate the utility of the Blueprints for the community nurses or clinic nurses
• To evaluate the fidelity to the Blueprint by the community nurses or clinic nurses
• To evaluate the utility of Facilitation Calls to improve implementation for the HIV clinic staff, community
nurses or clinic nurses
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Objectives
• Secondary objectives:
• Describe barriers and facilitators to implementation of CAB and RPV LA from the perspective of
HIV clinic staff, community nurses or clinic nurses
• Describe barriers and facilitators to implementation of CAB and RPV LA from the PWH
participant perspective
• Describe PWH participants’ preferences for the setting they receive injections and the reason for
their choice
• Describe any change in treatment satisfaction scores over time and by setting
• Describe the tolerability and acceptance of injections

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Study design

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Inclusion criteria

• Able and willing to complete informed consent prior to inclusion

• ≥ 18 years of age
• Documented HIV-1 infection
• Will receive CAB+ RPV as part of their routine clinical care
• In accordance with SmPC and NICE guidance:

Exclusion criteria
• Prior exposure to CAB + RPV LA
• Based on contraindication for CAB LA, RPV LA, in accordance with EU
license, MHRA license and NICE guidance:

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What is special about ILANA?

• Anti-racist, anti-sexist, anti-ageist study design

• Male and White participants capped at 50%, pts < 50 capped at 70%

• Aim to enroll women and people from racially minoritised backgrounds

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 Recruitment strategy
• Each site to recruit 18 participants

• List of people who want LA ART and are willing to wait for ILANA

• Willing to have CAB/LA in the community in 2nd six months

• Willing to consent to interviews and questionnaires

• Need to maintain list so people aren’t repeatedly approached

• It will take time for clinics to offer to everyone however, everyone will receive
it
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Final goal of ILANA

• This trial will observe in a real-world setting to see how feasible and acceptable
injectable HIV medication is and whether patients prefer in a clinic or
community setting.

• So, watch this space!

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 www.shareresearch.org.uk
www.qmul.ac.uk/share

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