Low resistance in clinical trials reinforced in the real world

Interpret results using real-world limitations.

In clinical trials, resistance was rare and manageable

  PIVOTAL TRIALS  
OUTCOME ATLAS & FLAIR3
n=591 (ITT-E)
Week 48		 ATLAS-2M7
n=1045 (ITT-E)
Week 152		 SOLAR1
n=447 (mITT-E)
Month 12
    ONCE-MONTHLY
(n=523)		 EVERY-2-MONTH
(n=522)		  
Virologically suppressed 93% 86% 87% 90%
CVF 1%
(n=6)		 0.4%
(n=2)		 2.3%
(n=12)		 0.4%
(n=2)
CVF with resistance 1%
(n=6)		 0.4%
(n=2)		 1.9%
(n=10)		 0.4%
(n=2)
CVF with treatment-emergent* resistance 0.7%
(n=4)		 0.4%
(n=2)		 1.5%
(n=8)		 0.4%
(n=2)
Re-suppression 5/6
PI- and INSTI-based regimens		 2/2
PI- and INSTI-based regimens		 11/12
PI- and INSTI-based regimens		 2/2
PI- and INSTI-based regimens
With ~2000 patients in clinical trials receiving CABENUVA, <1% experienced treatment-emergent resistance; and the majority of CVFs occurred in the first 6 months of therapy (n=13/22).1-3*
  PIVOTAL TRIALS
OUTCOME ATLAS & FLAIR3
n=591 (ITT-E)
Week 48		 ATLAS-2M7
n=1045 (ITT-E)
Week 152
    ONCE-MONTHLY
(n=523)
Virologically suppressed 93% 86%
CVF 1%
(n=6)		 0.4%
(n=2)
CVF with resistance 1%
(n=6)		 0.4%
(n=2)
CVF with treatment-emergent* resistance 0.7%
(n=4)		 0.4%
(n=2)
Re-suppression 5/6
PI- and INSTI-based regimens		 2/2
PI- and INSTI-based regimens
With ~2000 patients in clinical trials receiving CABENUVA, <1% experienced treatment-emergent resistance; and the majority of CVFs occurred in the first 6 months of therapy (n=13/22).1-3*
  PIVOTAL TRIALS  
OUTCOME ATLAS-2M7
n=1045 (ITT-E)
Week 152		 SOLAR1
n=447 (mITT-E)
Month 12
  EVERY-2-MONTH
(n=522)		  
Virologically suppressed 87% 90%
CVF 2.3%
(n=12)		 0.4%
(n=2)
CVF with resistance 1.9%
(n=10)		 0.4%
(n=2)
CVF with treatment-emergent* resistance 1.5%
(n=8)		 0.4%
(n=2)
Re-suppression 11/12
PI- and INSTI-based regimens		 2/2
PI- and INSTI-based regimens
With ~2000 patients in clinical trials receiving CABENUVA, <1% experienced treatment-emergent resistance; and the majority of CVFs occurred in the first 6 months of therapy (n=13/22).1-3*

CVF was defined as 2 consecutive HIV-1 RNA levels ≥200 copies/mL.

*Resistance that emerged from cabotegravir and/or rilpivirine that was detected at the time of virologic failure.

Most patients who met CVF re-suppressed on alternative, highly suppressive ARTs.1,3,6,7

When switching to CABENUVA, rates of CVF were similar and low

OUTCOME BEYOND4,5
n=160		 OPERA6
n=1293
Virologically suppressed 97% 95%
CVF 1%
(n=2)

The 2 CVFs transitioned to oral, INSTI-based, single-tablet regimens.5

There were NO NEW CVFs identified between Months 6 and 24.		 2%
(n=25)

SIMILAR RATE OF CVF observed between participants switching to CABENUVA or a new oral therapy (3%).*
Re-suppression Data not available 15/19
The most common regimens patients switched to were oral, INSTI-based.

In OPERA6

  • Following CVF, patients in each group had similar rates of virologic re-suppression†
  • The most common regimens switched to were oral, INSTI-based regimens

CVF was defined as 2 HIV-1 RNA measurements ≥200 copies/mL or 1 HIV-1 RNA ≥200 copies/mL plus discontinuation.

*Adjusted odds ratio (95% CI): 0.64 (0.4 to 1.02).

†Among those with a viral load available post-CVF, HIV-1 RNA <200 copies/mL: 95% (18/19) of patients previously treated with CABENUVA and 84% (36/43) of those previously treated with oral ART. HIV-1 RNA <50 copies/mL: 79% (15/19) of patients previously treated with CABENUVA and 72% (31/43) of those previously treated with oral ART.

  • OPERA Study Design

    Includes routine clinical data from EHRs* from 101 clinics across 23 US states and territories6

    • Overall, the OPERA database represents ~14% of people with HIV in the US
    Endpoints
    • Virologic outcomes among those with at least 1 follow-up HIV-1 RNA available
      • HIV-1 RNA <50 copies/mL
      • Confirmed virologic failure
    Censoring criteria
    • Discontinuation of ART regimen of interest
    • Death
    • 12 months after last clinical contact
    • End of analysis period June 30, 2023

    Real-world studies are designed to complement clinical trial data, not definitively establish causality. Data may better reflect actual patient populations and clinical care. Data are susceptible to bias. Observational studies have the potential for missing, inaccurate, incomplete, or overlapping data.

    *Includes patients switched to CABENUVA or a new oral ART regimen between January 21, 2021, and December 31, 2022.

    †Suppression defined as plasma HIV-1 RNA <50 copies/mL.

  • BEYOND Study Design

    Prospective, observational, real-world study of participants with HIV initiating CABENUVA across 27 US sites4,5

    • Analyses based on 233 participants initiating CABENUVA and determined to be consistent with the indication
    Primary outcomes
    • Reasons for initiating CABENUVA
    • Demographic characteristics
    • Clinical characteristics of participants upon initiation
    Key secondary outcomes
    • Virologic outcomes, including suppression* and CVF
    • Discontinuation of CABENUVA

    Real-world studies are designed to complement clinical trial data, not definitively establish causality. Data may better reflect actual patient populations and clinical care. Data are susceptible to bias. Observational studies have the potential for missing, inaccurate, incomplete, or overlapping data.

    *Suppression defined as plasma HIV-1 RNA <50 copies/mL.

  • Study Designs

    Trial Design Baseline Characteristics Primary Endpoint
    ATLAS8 Once-monthly CABENUVA vs daily oral ART Pooled

    Median age, 38 years
    Female, 27%
    White, 73%    		 Pooled

    HIV-1 RNA ≥50 copies/mL at W48: 1.9% vs 1.7%,
    adjusted difference 0.16 (95% CI -1.35, 1.67)
    FLAIR8 Once-monthly CABENUVA vs TRIUMEQ
    ATLAS-2M4 Once-monthly vs Every-2-month CABENUVA Median age, 42 years
    Female, 27%
    White, 73%    		 HIV-1 RNA ≥50 copies/mL at W48: 2% vs 1%,
    adjusted difference 0.8 (95% CI -0.6, 2.2)
    SOLAR1 Every-2-month CABENUVA vs BIKTARVY Median age, 37 years
    Female, 18%
    White, 69%    		 HIV-1 RNA ≥50 copies/mL at W48: 1% vs <1%, adjusted difference 0.7 (95% CI -0.7, 2.0)
    Trial Design Baseline Characteristics
    ATLAS8 Once-monthly CABENUVA vs daily oral ART Pooled

    Median age, 38 years
    Female, 27%
    White, 73%
    FLAIR8 Once-monthly CABENUVA vs TRIUMEQ
    ATLAS-2M4 Once-monthly vs Every-2-month CABENUVA Median age, 42 years
    Female, 27%
    White, 73%
    SOLAR1 Every-2-month CABENUVA vs BIKTARVY Median age, 37 years
    Female, 18%
    White, 69%
    Trial Primary Endpoint
    ATLAS8 Pooled

    HIV-1 RNA ≥50 copies/mL at W48: 1.9% vs 1.7%,
    adjusted difference 0.16 (95% CI -1.35, 1.67)
    FLAIR8
    ATLAS-2M4 HIV-1 RNA ≥50 copies/mL at W48: 2% vs 1%,
    adjusted difference 0.8 (95% CI -0.6, 2.2)
    SOLAR1 HIV-1 RNA ≥50 copies/mL at W48: 1% vs <1%, adjusted difference 0.7 (95% CI -0.7, 2.0)

OPERA

An observational study of US adults after a switch to CABENUVA or a new oral therapy6

  • At baseline in the CABENUVA arm, the median age was 39, 17% were female, and 41% were Black/African American. Includes patients started on either once-monthly or every-2-month CABENUVA

BEYOND

A prospective, observational study of US adults switching to CABENUVA4

  • At baseline, the mean age was 46, 12% were female, and 49% were White. Includes patients started on either once-monthly or every-2-month CABENUVA

Real-world studies are designed to complement clinical trial data, not definitively establish causality. Data may better reflect actual patient populations and clinical care. Data are susceptible to bias. Observational studies have the potential for missing, inaccurate, incomplete, or overlapping data.

Robust clinical trial program + real-world studies

See clinical trial results

Explore real-world studies

ART=antiretroviral therapy; CI=confidence interval; CVF=confirmed virologic failure; EHR=electronic health record; INSTI=integrase strand-transfer inhibitor; ITT-E=intent-to-treat exposed; PI=protease inhibitor.

References:

  1. Ramgopal MN, Castagna A, Cazanave C, et al. Efficacy, safety, and tolerability of switching to long-acting cabotegravir plus rilpivirine versus continuing fixed-dose bictegravir, emtricitabine, and tenofovir alafenamide in virologically suppressed adults with HIV, 12-month results (SOLAR): a randomised, open-label, phase 3b, non-inferiority trial. Lancet HIV. 2023;10(9):E566-E577. doi.org/10.1016/S2352-3018(23)00136-4
  2. Overton ET, Richmond G, Rizzardini G, et al. Long-acting cabotegravir and rilpivirine dosed every 2 months in adults with HIV-1 infection (ATLAS-2M), 48-week results: a randomised, multicentre, open-label, phase 3b, non-inferiority study. Lancet. 2020;396(10267):1994-2005. doi:10.1016/S0140-6736(20)32666-0
  3. Rizzardini G, Overton ET, Orkin C, et al. Long-acting injectable cabotegravir + rilpivirine for HIV maintenance therapy: week 48 pooled analysis of phase 3 ATLAS and FLAIR trials. J Acquir Immune Defic Syndr. 2020;85(4):498-506.
  4. Blick G, Santiago-Colon L, Richardson D, et al. Clinical outcomes at month 24 after initiation of cabotegravir and rilpivirine long-acting (CAB+RPV LA) in an observational real-world US study (BEYOND). Presented at the 13th IAS Conference on HIV Science; July 13-17, 2025; Kigali, Rwanda, and virtually. EP1078.
  5. Dandachi D, Garris C, Richardson D, et al. Clinical outcomes and perspectives of people with human immunodeficiency virus type 1 twelve months after initiation of long-acting cabotegravir and rilpivirine in an observational real-world US study (BEYOND). Open Forum Infect Dis. 2025;12(5):ofaf220. doi:10.1093/ofid/ofaf220
  6. Hsu RK, Sension M, Fusco JS, et al. Real-world effectiveness of cabotegravir + rilpivirine vs standard of care oral regimens in the US. Poster presented at: Retroviruses and Opportunistic Infections (CROI); March 3-6, 2024; Denver, CO.
  7. Overton ET, Richmond G, Rizzardini G, et al. Long-acting cabotegravir and rilpivirine dosed every 2 months in adults with human immunodeficiency virus 1 type 1 infection: 152-week results from ATLAS-2M, a randomized, open-label, phase 3b, noninferiority study. Clin Infect Dis. 2023;76(9):1646-1654.

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