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IT IS TIME TO THINK BEYOND
SUPPRESSION

BEYOND VIRAL SUPPRESSION

DOVATO HAS DEMONSTRATED NO CLINICALLY SIGNIFICANT METABOLIC HEALTH* IMPACT IN SWITCH PATIENTS

Metabolic Health Parameters Reported in Studies did not determine if these changes translate into clinical differences

Metabolic health outcomes in the TANGO and SALSA studies

  • Small changes with generally favourable lipid results vs TAF-containing regimens

  • Similar small increases in metabolic syndrome across arms†

  • Similar small changes in fasting glucose across arms†

  • Similar small increases in HOMA-IR‡ levels across arms

OUT TO 144 WEEKS IN SWITCH PATIENTS[1,2]
Metabolic health outcomes in the TANGO and SALSA studies

  • Changes in lipid parameters were small and similar between treatment arms

OUT TO 48 WEEKS IN SWITCH PATIENTS[3]
RUMBA

  • Small changes in HDL cholesterol favouring DOVATO vs. BIC/FTC/TAF

  • Similar changes in other lipid parameters across arms

  • Similar changes across HOMA-IR across arms

OUT TO 48 WEEKS IN SWITCH PATIENTS[4]

*“Metabolic health” is an umbrella term for several metabolic variables that are associated with developing cardiometabolic disease.
†Metabolic syndrome defined by the International Diabetes Federation as a combination of risk factors for cardiovascular disease.[4]
‡Defined as homeostatic model assessment of insulin resistance (HOMA-IR) ≥2.[1]

IN CLINICAL STUDIES, DOVATO WAS ALSO ASSOCIATED WITH SMALL WEIGHT CHANGES

GEMINI-1 and 2 study icon
GEMINI-1 and 2 study icon

  • +3.7 kg in DOVATO arm vs +2.4 kg in DTG + TDF/FTC arm*

OUT TO 144 WEEKS IN TREATMENT-NAÏVE PATIENTS[5]
STAT study icon

  • +4.9 kg (median)

OUT TO 48 WEEKS IN NEWLY DIAGNOSED PATIENTS[6]
TANGO study icon

  • +2.2kg in DOVATO arm vs +1.7kg in TAF-containing regimens arm*
     

    Change in weight, both adjusted mean and ≥10% increase, was similar between arms in participants with baseline TAF use

OUT TO 144 WEEKS IN SWITCH PATIENTS[1]
SALSA study icon

  • +2.1 kg in DOVATO arm vs +0.6 kg in continued current regimens arm*
     

    Changes in weight, both adjusted mean (2.4 kg vs 0.1 kg) and ≥10% increase, were higher in the DOVATO arm in participants with baseline TDF use (14% vs 3%)
     

    Change in weight, both adjusted mean and ≥10% increase, was similar between arms in participants with baseline TAF use; change in weight was higher in the DOVATO arm in participants with baseline TDF use

OUT TO 48 WEEKS IN SWITCH PATIENTS[3,7]
RUMBA

  • No significant difference between arms with regard to weight (+0.26kg in DOVATO arm vs +0.18kg in the BIC/FTC/TAF arms), BMI, and waist circumference

  • Small changes in lean trunk mass and fat percentage favouring DOVATO

OUT TO 48 WEEKS IN SWITCH PATIENTS[4]

DTG 50 mg + 3TC 300 mg used in the GEMINI studies.
*Mean weight changes reported unless otherwise noted.
†≥10% weight gain.

WHAT WEIGHT CHANGES HAVE BEEN OBSERVED WITH OTHER ARTs?

  • Weight Gain: Treatment Naïve

    INCREASED WEIGHT GAIN WITH TAF AND INIs IN TREATMENT-NAÏVE PATIENTS

    In a Pooled Analysis of 8 Treatment-Naïve RCTs (N=5,680)[8]:

    TAF Was Associated With Weight Gain at 96 Weeks

    LS mean weight change over time in patients taking NRTIs*[8]

    Chart showing change in weight over time in patients taking NRTIs

    TAF was also associated with an increased risk of a clinically meaningful† weight gain compared with ABC (OR, 1.90 [95% CI: 1.25–2.88]; P=0.003) and TDF (OR, 1.47 [95% CI: 1.14–1.90]; P=0.003).

    BIC and DTG Were Associated With a Significantly Increased Risk of Weight Gain Compared With Boosted EVG at 96 Weeks

    LS mean weight change over time in patients taking INIs*[8]

    Chart showing weight change over time in patients taking INIs

    Adapted from Sax et al, 2020.[8]

    BIC and DTG (OR, 1.82 [95% CI: 1.24–2.66]; P=0.002), and EVG/c (OR, 1.36 [95% CI: 1.04–1.78]; P=0.026), were also associated with an increased risk of a clinically meaningful† weight gain compared with EFV.

    Asterisks are colour-coded to match the respective comparator and denote P≤0.05 compared with EVG/c.[8]

    LS=least squares; OR=odds ratio.
    *Multivariate model; stepwise model selection was used to identify baseline risk factors.[8]
    †≥10% weight gain.

  • Weight Gain: TDF to TAF

    INDEPENDENT RISK OF WEIGHT GAIN WITH TAF: TDF⟶TAF SWITCH

    Outcomes Demonstrated Across RCTs and Real-World Data

    Pooled Analysis of 12 Suppressed-Switch RCTs (N=7,316): Switching From TDF to TAF Associated With Significant Weight Gain at 48 Weeks

    LS mean weight change over time*[9]

    Chart showing change in weight over time in patients switching from TDF to TAF

    Adapted from Erlandson et al, 2021.[7]

    Switching from TDF to TAF was associated with ≥10% weight gain.

    OPERA Cohort: Adjusted Predicted Weight Over Time Before and After TDF to TAF Switch Among Patients Who Maintained All Other ARVs (n=5,479)[10]

    Chart showing weight change over time from the OPERA cohort.

    Republished from Mallon et al, 2021[10] under the Creative Commons Attribution (CC-BY 4.0).

    Asterisks indicate P<0.05 compared with the stay-on baseline regimen weight change.[9]
    LS=least squares.
    *Stepwise model selection was used to identify baseline risk factors associated with change in weight following switch, using linear mixed effects models.[9]

  • Weight Gain: ABC to TAF

    INDEPENDENT RISK OF WEIGHT GAIN WITH TAF: ABC⟶TAF SWITCH

    Outcomes Demonstrated Across RCTs and Real-World Data

    Pooled Analysis of 12 Suppressed-Switch RCTs (N=7,316): Switching From ABC to TAF Associated With Significant Weight Gain at 48 Weeks

    LS mean weight change over time*[9]

    Chart showing change in weight over time for patients switching from ABC to TAF associated with significant weight gain.

    Adapted from Erlandson et al, 2021.[9]
    Statistical analyses not reported.

    Swiss Cohort: Adjusted Median Weight Gain Through 18 Months in Patients (N=2,987) Who Received ABC and Continued ABC or Switched to TAF[11]

    Chart showing change in weight over time for patients in the Swiss cohort.

    Adapted from Surial et al, 2021.[11]

    Asterisks indicate P<0.05 compared with the stay-on baseline regimen weight change.[9]
     LS=least squares.
    *Stepwise model selection was used to identify baseline risk factors associated with change in weight following switch, using linear mixed effects models.[9]

    BONE AND RENAL PARAMETERS ACROSS STUDIES

    These studies did not determine if these changes translate to clinical differences

    GEMINI-1 and 2 study icon
    GEMINI-1 and 2 study icon

    • Small changes in renal function and bone biomarkers from baseline, with improvements favouring DOVATO vs DTG + TDF/FTC
       

      AEs due to renal and urinary disorders were comparable across both arms

    OUT TO 144 WEEKS IN TREATMENT-NAÏVE PATIENTS[5]
    TANGO study icon

    • Small and similar changes in bone biomarkers across both arms out to 144 weeks

    • Small and similar changes in renal biomarkers across both arms out to 144 weeks

    OUT TO 144 WEEKS IN SWITCH PATIENTS[1,12]
    SALSA study icon

    • Similar small changes in eGFR from cystatin C were observed in both treatment groups; decrease in eGFR were observed in both treatment groups, with a greater decrease with DOVATO

    • Small changes in bone biomarkers favoured DOVATO vs continued regimens

    OUT TO 48 WEEKS IN SWITCH PATIENTS[3]

    DTG 50 mg + 3TC 300 mg used in the GEMINI studies.
    AE=adverse event.

    Want to hear from the experts, including past webinar recordings?

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    Durable and robust suppression[1,5]

    See the data

    High barrier to resistance

    See the data

References:

  1. Osiyemi O, De Wit S, Ajana F, et al. Efficacy and safety of switching to dolutegravir/lamivudine (DTG/3TC) versus containing a tenofovir alafenamide-based 3- or 4-drug regimen for maintenance of virologic suppression in adults living with HIV-1: results through week 144 from the phase 3, non-inferiority TANGO randomized trial. Clin Infect Dis. 2022;ciac036 and suppl 1-18. doi:10.1093/cid/ciac036
  2. van Wyk J, Ait-Khaled M, Santos J, et al. Metabolic health outcomes at week 144 in the TANGO study, comparing a switch to DTG/3TC versus maintenance of TAF-based regimens. Presented at: The 11th International AIDS Society Conference on HIV Science; July 18-21, 2021; Virtual. Poster PEB164.
  3. Llibre JM, Alves Brites C, Cheng C-Y, et al. Switching to the 2-drug regimen of dolutegravir/lamivudine (DTG/3TC) fixed-dose combination is non-inferior to continuing a 3-drug regimen through 48 weeks in a randomized clinical trial (SALSA). Presented at: The 11th International AIDS Society Conference on HIV Science; July 18-21, 2021; Virtual. Slides OALB0303.
  4. DeGroote S, Vanherrewage S, Tobback E, et. al. Understanding changes in metabolic parameters switching to 2DR from 3DR Integrase Strand Inhibitors (InSTIs). Presented at HIV Glasgow 2022; October 23-26, 2022. Glasgow, UK. Poster.
  5. International Diabetes Federation. The IDF consensus worldwide definition of the metabolic syndrome. Published 2006. Accessed June 25, 2024. https://idf.org/media/uploads/2023/05/attachments-30.pdf
  6. Cahn P, Sierra Madero J, Arribas JR, et al. Three-year durable efficacy of dolutegravir plus lamivudine in antiretroviral therapy-naïve adults with HIV-1 infection. AIDS. 2022;36(1):39-48. doi:10.1097/QAD.0000000000003070
  7. Rolle C-P, Berhe M, Singh T, et al. Dolutegravir/lamivudine as a first-line regimen in a test-and-treat setting for newly diagnosed people living with HIV. AIDS. 2021;35(12):1957-1965. doi:10.1097/QAD.0000000000002979
  8. Hagins D, Mussini C, Zhang F, et al. Week 48 metabolic health after switch to DTG/3TC vs CAR by baseline regimen (SALSA). Presented at: Conference on Retroviruses and Opportunistic Infections; February 12-16, 2022; Virtual. Poster 603.
  9. Sax PE, Erlandson KM, Lake JE, et al. Weight gain following initiation of antiretroviral therapy: risk factors in randomized comparative clinical trials. Clin Infect Dis. 2020;71(6):1379-1389. doi:10.1093/cid/ciz999
  10. Erlandson KM, Carter CC, Melbourne K, et al. Weight change following antiretroviral therapy switch in people with viral suppression: pooled data from randomized clinical trials. Clin Infect Dis. 2021;73(8):1440-1451. doi:10.1093/cid/ciab444
  11. Mallon PWG, Brunet L, Hsu RK, et al. Weight gain before and after switch from TDF to TAF in a US cohort study. J Int AIDS Soc. 2021;24(4):e25702. http://onlinelibrary.wiley.com/doi/10.1002/jia2.25702/full
  12. Surial B, Mugglin C, Calmy A, et al; for the Swiss HIV Cohort Study. Weight and metabolic changes after switching from tenofovir disoproxil fumarate to tenofovir alafenamide in people living with HIV. Ann Intern Med. 2021;174(6):758-767. doi:10.7326/M20-4853
  13. van Wyk J, Ajana F, Bisshop F, et al. Switching to DTG/3TC fixed-dose combination (FDC) is non-inferior to continuing a TAF-based regimen in maintaining virologic suppression through 48 weeks (TANGO study). Presented at: International AIDS Conference; July 21-24, 2019; Mexico City, Mexico. Slides WEAB0403LB.

July 2024 PM-GB-DLL-WCNT-220003 v2

Prescribing Information

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