ATLAS-2M

EFFICACY

  • ATLAS-2M Study Design

    Virologically suppressed adults (≥18 years) with HIV-1:1-3


    Selected exclusion criteria1:

    • 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).2

    †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.1

    ‡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.1

    §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.1

    ||Oral lead-in regimen consisting of 30-mg cabotegravir and 25-mg rilpivirine given once daily for 4 weeks.1

    Patients transitioning from the ATLAS trial with once-monthly exposure to CABENUVA received their first injections on Day 1.1

  • ATLAS-2M Baseline Characteristics

    Baseline patient characteristics1
      Every-2-month CABENUVA
    (n=522)    		 Once-monthly CABENUVA
    (n=523)
    Age, median years (IQR)
    Range    		 42 (34 to 51)
    20 to 83    		 42 (34 to 50)
    19 to 75
    Sex assigned at birth,* %
    Male
    Female
    74
    26
    73
    27
    Race, %
    White
    Black/African American
    Other
    71
    19
    10
    75
    17
    8
    Hispanic or Latino ethnicity, % 14 12
    Median BMI, kg/m2 (IQR)
    BMI range
    BMI ≥30    		 26 (23 to 29)
    18 to 48
    113 (22%)    		 26 (23 to 29)
    17 to 78
    98 (19%)
    T-cell count ≥350 cells/µL, % (IQR) 642 (499 to 827)
    93    		 688 (523 to 878)
    95
      Every-2-month CABENUVA
    (n=522)    		 Once-monthly CABENUVA
    (n=523)
    Age, median
    years (IQR)
    Range    		 42 (34 to 51)

    20 to 83    		 42 (34 to 50)

    19 to 75
    Sex
    assigned at
    birth,* %
    Male
    Female


    74
    26


    73
    27
    Race, %
    White
    Black/African
    American
    Other
    71
    19

    10
    75
    17

    8
    Hispanic or Latino ethnicity, % 14 12
    Median BMI,
    kg/m2 (IQR)
    BMI range
    BMI ≥30    		 26 (23 to 29)

    18 to 48
    113 (22%)    		 26 (23 to 29)

    17 to 78
    98 (19%)
    T-cell count ≥350 cells/µL, % (IQR) 642 (499 to 827)
    93    		 688 (523 to 878)
    95

    *8 patients who were assigned male at birth identified as female at enrollment.

  • ATLAS-2M: Efficacy

    ATLAS-2M: ITT-E FDA snapshot virologic outcomes through Week 152 

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

    †One patient who was included as a CVF did not meet the protocol defined criteria but was included due to a viral load of ≥200 copies/mL measured at study site using a non-protocol–specific assay.1,3

  • ATLAS-2M: CVF

    CVF with resistance observed in patients receiving CABENUVA in ATLAS-2M1,3-4

    As a prespecified secondary endpoint, patients who met the protocol-defined CVF criteria (14/1045) were tested for emergent INSTI (cabotegravir) or NNRTI (rilpivirine) substitutions conferring resistance by 152 weeks.3

     Resistance-associated mutations in patients who meet protocol-defined CVF1,3-4
      EVERY-2-MONTH CABENUVA
    (n=522)    		 ONCE-MONTHLY CABENUVA
    (n=523)
    Patients with CVF, n (%) 12 (2)* 2 (<1)
    INSTI resistance-associated mutations† N155N/H+Q148Q/R (n=2),
    T97A+N155H, N155H, Q148R (n=3)    		 N155N/H and Q148+E138E/K
    NNRTI resistance-associated mutations† K103N, K101E, Y188L, Y188L+P225H, K101E+E138A, E138A+K103N, E138E/K, K101E+M230L, K103N+Y181C, E138K, E138A+M230M/L, E138A+Y181Y/C K101E+M230L

    All clinical isolates from patients who failed with resistance (exploratory analysis)1,3-4

    • Maintained phenotypic susceptibility to multiple ARVs, including dolutegravir, bictegravir, boosted PIs, and/or nearly all NNRTIs
    • 13 of the 14 patients who failed re-suppressed on oral ART
    • 1 patient who failed to achieve re-suppression reported poor adherence to PI-based ARV therapy 

    *One patient who was included as CVF did not meet the protocol-defined criteria but was included due to a viral load ≥200 copies/mL measured at study site using a non-protocol specified assay.

    †Suspected virologic failure time point.

    Resistance data in clinical trials reinforced in the real world

    Real-world CVF

ATLAS-2M

SAFETY

  • Drug-related adverse events through Week 152<sup>2,3</sup>

    ATLAS-2M: The majority of adverse reactions were Grade 1-2 ISRs and were the most common side effect associated with CABENUVA in both arms, the majority of which were mild to moderate and short in duration.3 

    Drug-related AEs* Occurring in ≥1% of Patients in Either Group2
      EVERY 2-MONTH CABENUVA
    (n=522)    		 ONCE-MONTHLY CABENUVA
    (n=523)
    ISRs 81% 79%
    Pyrexia† 9% 10%
    Fatigue‡ 5% 8%
    Musculoskeletal pain§ 3% 4%
    Diarrhea 2% <1%
    Dizziness 2% 2%
    Headache 2% 2%
    Pain 2% 2%
    Nausea 1% 2%
    Rash‖ 1% 1%
    Weight increased 1% <1%
    Presyncope <1% 1%
    Sleep disorders <1% 2%
    Discontinuation rate due to drug-related AEs 2% 3%

    *Adverse reactions defined as “treatment-related” as assessed by the investigator.

    †Pyrexia: includes pyrexia, feeling hot, chills, influenza-like illness, body temperature increased. 

    ‡Fatigue: includes fatigue, malaise, asthenia. 

    §Musculoskeletal pain: includes musculoskeletal pain, musculoskeletal discomfort, back pain, myalgia, pain in extremity.

    ||Rash: includes erythema, pruritus, pruritus generalized, purpura, rash, rash-erythematous, generalized, macular. 

    Sleep disorders: includes insomnia, poor quality sleep, somnolence.

  • ATLAS-2M: ISRs through Week 152<sup>1,3-4</sup>

    • Rate of ISRs at each visit decreased over the first 48 weeks and remained consistent thereafter
      • Self-reported ISRs could potentially underestimate the true rate of ISRs over time; ISRs may still be present but not reported during the study
    • Discontinuations due to injection-related reasons: every-2-month=2%, once-monthly=3%
    • Median (IQR) duration was 3 (2-5) days in both arms

When it's time for CABENUVA, we have resources

Discover access resources

AE=adverse event; ART=antiretroviral therapy; ARV=antiretroviral; ATV=atazanavir; BMI=body mass index; CI=confidence interval; CVF=confirmed virologic failure; HBV=hepatitis B virus; INSTI=integrase strand-transfer inhibitor; IQR=interquartile range; ISR=injection site reaction; ITT-E=intent-to-treat exposed; M=month; NNRTI=non-nucleoside reverse transcriptase inhibitor; NRTI=nucleoside reverse transcriptase inhibitor.

References:

  1. 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 randomized, multicentre, open-label phase 3b, non-inferiority study. Lancet. 2020;396(10267):1994-2005. doi:10.1016/S0140-6736(20)326666-0
  2. Data on file. ViiV Healthcare group of companies. Durham, NC.
  3. 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.
  4. Jaeger H, Overton ET, Richmond G, et al. Long-acting cabotegravir and rilpivirine dosed every 2 months in adults with HIV-1 infection (ATLAS-2M), 96-week results: a randomised, multicentre, open-label, phase 3b, non-inferiority study. Lancet HIV. 2021;8(11):e679-e689. doi:10.1016/S2352-3018(21)00185-5

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