Real-world studies are designed to evaluate associations among variables and not to definitively establish causality. These results are descriptive. Data are susceptible to bias. Observational studies have the potential for missing, inaccurate, incomplete, or overlapping data.

Low rates of resistance in clinical trials reinforced in the real world

  RANDOMIZED CLINICAL TRIALS REAL-WORLD EVIDENCE
OUTCOME ATLAS & FLAIR3
n=591 (ITT-E)
Week 48		 ATLAS-2M2
n=1045 (ITT-E)
Week 152		 SOLAR1
n=447 (mITT-E)
Month 12		 SLR4
N=13,899
CVF or VF (RWE) 1%
(n=6)		 ONCE-MONTHLY
0.4% (n=2)		 EVERY-2-MONTH
2.3% (n=12)		 0.4%
(n=2)		 1.2%
(172/13,899)‡
CVF or VF (RWE) with resistance 1%
(n=6)		 0.4%
(n=2)		 1.9%
(n=10)		 0.4%
(n=10)		 0.7%
(52/8117)†
Re-suppression
after CVF or
VF (RWE)		 5/6
PI- and INSTI-based regimens		 13/14
PI- and INSTI-based regimens		 2/2
PI- and INSTI-based regimens		 65/74†
The most common regimens switched to included oral INSTI-based regimens§
  RANDOMIZED CLINICAL TRIALS
OUTCOME ATLAS & FLAIR3
n=591 (ITT-E)
Week 48
CVF or VF (RWE) 1%
(n=6)
CVF or VF (RWE) with resistance 1%
(n=6)
Re-suppression
after CVF or
VF (RWE)		 5/6
PI- and INSTI-based regimens
  RANDOMIZED CLINICAL TRIALS
OUTCOME ATLAS-2M2
n=1045 (ITT-E)
Week 152
CVF or VF (RWE) ONCE-MONTHLY
0.4% (n=2)		 EVERY-2-MONTH
2.3% (n=12)
CVF or VF (RWE) with resistance 0.4%
(n=2)		 1.9%
(n=10)
Re-suppression
after CVF or
VF (RWE)		 13/14
PI- and INSTI-based regimens
  RANDOMIZED CLINICAL TRIALS
OUTCOME SOLAR1
n=447 (mITT-E)
Month 12
CVF or VF (RWE) 0.4%
(n=2)
CVF or VF (RWE) with resistance 0.4%
(n=10)
Re-suppression
after CVF or
VF (RWE)		 2/2
PI- and INSTI-based regimens
  REAL-WORLD EVIDENCE
OUTCOME SLR4
N=13,899
CVF or VF (RWE) 1.2%
(172/13,899)‡
CVF or VF (RWE) with resistance 0.7%
(52/8117)†
Re-suppression
after CVF or
VF (RWE)		 65/74†
The most common regimens switched to included oral INSTI-based regimens§

*7987 patients were included in cohorts with genotypic data available. Of these, there were 80 VF events with genotypic data available; 28 had no RAMs observed.

†8117 patients were included in cohorts with re-suppression outcomes after VF available. Of these, there were 74 VF events with a known re-suppression outcome; 9 did not resuppress.

‡The definition used for virologic failure varied between studies.

§8521 patients were included in cohorts with post-VF regimen data available. Of these, there were 92 VF events with post-VF regimen data available. Of these, 66 received an oral regimen, which included PI-based (47%, n=31/66), INSTI-based (44%, n=29/66), and other (9%, n=6/66) regimens.

  • ATLAS & FLAIR Study Designs

    *≥18 years of age.5

    †HIV-1 RNA <50 copies/mL.5

    ‡Third agent included INSTI, NNRTI, or PI.5

    §Oral lead-in regimen consisted of 30-mg cabotegravir and 25-mg rilpivirine once daily for at least 1 month.

    ||On the last day of the oral lead-in, patients received initiation injections of cabotegravir and rilpivirine followed by continuation injections 1 month later and then monthly thereafter.

    Defined as ≤10 days of prior therapy with any ARV following a diagnosis of HIV-1 infection. Screening HIV-1 RNA ≥1000 copies/mL.6

    #Or DTG + 2 NRTIs if HLA-B*5701-positive.6

    **Patients required to have HIV-1 RNA <50 copies/mL by 4 weeks prior to randomization.6

  • ATLAS-2M Study Design

    Selected exclusion criteria9:

    • Previous virologic failure
    • Any known INSTI or NNRTI resistance (excluding K103N)
    • HBV infection at screening
    • Moderate to severe hepatic impairment
    • Women who were pregnant or breastfeeding, or planned to become pregnant or breastfeed

    *Acceptable ARV regimens (either initial or second ARV regimen) included 2 NRTIs plus an INSTI, NNRTI, or boosted PI (or ATV unboosted).8

    †Patients transitioning from the ATLAS trial who were on oral ART must have been on their current oral regimen for at least 52 weeks and had plasma HIV-1 RNA <50 copies/mL.9

    ‡Newly enrolled patients were virologically suppressed for at least 6 months on 2 NRTIs + third agent, with suppression defined as plasma HIV-1 RNA <50 copies/mL.9

    §Patients transitioning from ATLAS on once-monthly CABENUVA either completed at least 52 weeks in the comparative phase or switched from an oral regimen after Week 52 in the extension phase and had plasma HIV-1 RNA <50 copies/mL.9

    ||Oral lead-in regimen consisting of 30-mg cabotegravir and 25-mg rilpivirine given once daily for 4 weeks.9

    Patients transitioning from the ATLAS trial with once-monthly exposure to CABENUVA received their first injections on Day 1.9

  • SOLAR Study Design

    Primary endpoint (mITT-E population)

    Proportion of patients with HIV-1 RNA ≥50 copies/mL in the Month 12 analysis‡

    Secondary efficacy endpoint

    Proportion of patients with HIV-1 RNA <50 copies/mL in the Month 12 analysis

    Exclusion criteria
    • History of virologic failure
    • Known or suspected presence of resistance mutations to the individual components of BIKTARVY or CABENUVA
    • HBV infection at screening
    • Moderate to severe hepatic impairment
    • Women who were pregnant or breastfeeding or planned to become pregnant or breastfeed
    • Efficacy analyses, baseline questionnaire, and preference calculation were based on the mITT-E (N=670) population. After consultation with a blinded external expert, 11 participants at a single study site were excluded from the ITT-E population due to critical findings related to significant and persistent noncompliance to protocol requirements
    • Safety analyses were based on ITT-E (N=681) population

    *Suppression defined as plasma HIV-1 RNA <50 copies/mL. A single prior INSTI-based regimen was allowed for reasons other than treatment failure.

    †On last day of the OLI period or oral ART, patients received 2 sets of initiation CABENUVA injections 1 month apart followed by every-2-month injections thereafter.

    ‡Month 12 (OLI and BIKTARVY) and Month 11 (SWI).

  • SLR Study Design

    The SLR included real-world, observational cohort studies describing outcomes in virologically suppressed people with HIV published or presented between January 2020 and November 2024. Studies including <10 patients were excluded.4

Robust clinical trial program + real-world studies

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3TC=lamivudine; ABC=abacavir; ART=antiretroviral therapy; ARV=antiretroviral; ATV=atazanavir; CVF=confirmed virologic failure; DTG=dolutegravir; FDA=Food and Drug Administration; HBV=hepatitis B virus; INSTI=integrase strand-transfer inhibitor; ITT-E=intent-to-treat exposed; LA=long-acting; mITT-E=modified intent-to-treat exposed; NNRTI=non-nucleoside reverse transcriptase inhibitor; NRTI=nucleoside reverse transcriptase inhibitor; OLI=oral lead-in; PI=protease inhibitor; RAM=resistance associated mutation; RWE=real-world efficacy; SLR=systematic literature review; VF=virologic failure; SWI=starting with injections; W=Week.

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 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.
  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. Ring K, Elias A, Devonald M, Smuk M, Orkin C. Long-acting injectable cabotegravir and rilpivirine in observational cohort studies: a systematic review on virologic failure, resistance and re-suppression outcomes in virally suppressed individuals living with HIV. HIV Med. 2025;26(8):1267-1288.
  5. Swindells S, Andrade-Villanueva J-F, Richmond G, et al. Long-acting cabotegravir and rilpivirine for maintenance of HIV-1 suppression. N Engl J Med. 2020;382(12):1112-1123. doi:10.1056/NEJMoa1904398
  6. Orkin C, Arasteh K, Górgolas Hernández-Mora M, et al. Long-acting cabotegravir and rilpivirine after oral induction for HIV-1 infection. N Engl J Med. 2020;382(12):1124-1135. doi:10.1056/NEJMoa1909412
  7. Orkin C, Oka S, Philibert P, et al. Long-acting cabotegravir plus rilpivirine for treatment in adults with HIV-1 infection: 96-week results of the randomised, open-label, phase 3 FLAIR study. Lancet HIV. 2021;8:e185-e196.
  8. Data on file. ViiV Healthcare group of companies. Durham, NC.
  9. 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

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