TWO HEAD-TO-HEAD TRIALS COMPARING THE EFFICACY OF DOVATO VS BIKTARVY
DYAD: A Head-to-Head, Randomized (2:1), Open-Label, Noninferiority Trial of DOVATO vs BIKTARVY1
TRIAL DESIGN
222 Adult Participants Who Started on BIKTARVY Either Switched to DOVATO or Continued BIKTARVY1
DYAD is a single-center study conducted in the US.
Select Inclusion Criteria1
- Participants virologically suppressed on BIKTARVY for ≥3 months
- At least 2 documented measurements of HIV suppression on BIKTARVY at least 3 months apart
- Participants ≥18 years of age
- Stable form of insurance that was expected to continue without significant changes for at least 12 months
Select Exclusion Criteria1
- HBV infection or acute need for HCV therapy
- History of prior viral failure
- Suspected or documented INSTI resistance
- Major NRTI resistance
Primary Endpoint1
- Proportion of participants with HIV-1 RNA ≥50 copies/mL at Week 48 using the FDA Snapshot algorithm (ITT–E) and a 6% noninferiority margin
Secondary Endpoints1
- Proportion of participants with plasma HIV-1 RNA <50 copies/mL at Weeks 48, 96, and 144 in the ITT–E population
- Mean change in weight from baseline at Week 48, compared using 2-sample t-tests
*Observational phase follows participants after they exit DYAD in the real world and collects 96- and 144-week efficacy and safety data recorded in the electronic health record.1
BASELINE CHARACTERISTICS
On Average, Participants Were on ART for ~10 Years and Took 3 Prior ART Regimens1
| Baseline Characteristics | DOVATO (n=149) |
BIKTARVY (n=73) |
|---|---|---|
| Age, median (range), years | 49 (24-73) | 51 (20-73) |
| ≥50, n (%) | 74 (50%) | 44 (60%) |
| Female, n (%) | 24 (16%) | 12 (16%) |
| Race, n (%) | ||
| Caucasian | 102 (68%) | 54 (74%) |
| Black | 44 (30%) | 18 (25%) |
| Asian | 1 (1%) | 0 (0%) |
| Ethnicity, n (%) | ||
| Hispanic or Latino | 43 (29%) | 22 (30%) |
| Weight, median (range), kg | 90.4 (53.1–171.9) | 88.5 (59.1–123.5) |
| CD4+ T-cell count, median (range), cells/mm3 | 720.5 (214–1479) | 734.5 (151–1573) |
| Duration of ART prior to Day 1, median (range), years | 12 (1-32) | 9.5 (1-27) |
| Number of prior ART regimens | 3 (1-9) | 3 (1-10) |
| Participants with unknown genotype, n (%) | 89 (60%) | 36 (49%) |
| Insurance coverage, n (%) | ||
| Private | 132 (89) | 59 (81) |
| Medicare | 12 (8) | 10 (13) |
| Medicaid | 5 (3) | 2 (3) |
| Ryan White | 0 (0) | 2 (3) |
60%
of participants in the DOVATO arm had unknown resistance history1
The study population had a median age of ~50 years, 16% female, and ~30% non-white people living with HIV1
EFFICACY
DOVATO Was Noninferior to BIKTARVY at 48 Weeks,† With Fewer Medicines1
Virologic Outcomes at Week 48 by FDA Snapshot Analysis
Noninferiority criteria were not specified for the HIV-1 RNA <50 copies/mL endpoint.
There was no virologic data for 16 (11%) participants in the DOVATO arm and 9 (12%) participants in the BIKTARVY arm.
†Noninferiority analysis with a 6% margin using the Farrington-Manning Score Test.
RESISTANCE
A High Barrier to Resistance and No Cases of INSTI Resistance for DOVATO Through Week 481
Cases of CVW With Treatment-Emergent Resistance1§
| DOVATO (n=149) |
BIKTARVY (n=73) |
|
|---|---|---|
| 2 consecutive viral loads ≥50 copies/mL‡ | 12 (8.1%) | 6 (8.2%) |
| And with treatment-emergent resistance§‖ | 1 | 1 |
| Cases of treatment-emergent resistance by type | ||
| NRTI resistance | 1 | 1 |
| INSTI resistance | 0 | 1 |
0
cases of INSTI resistance were reported in the DOVATO arm through Week 48 vs 1 case in the BIKTARVY arm1
‡Only participants meeting this criteria were assessed for treatment-emergent resistance.
§One non-CVW DOVATO participant developed SVF at Week 4 with an HIV-1 RNA of 148 copies/mL but did not return for confirmatory resting. At Week 12, HIV-1 RNA was 87 copies/mL and a genotype was inadvertently collected at this initial episode of unconfirmed viremia. Genotypic testing demonstrated K65R, M184V, T219E. The participant was discontinued from the trial at Week 12, at which time they had an HIV-1 RNA <50 copies/mL on DOVATO. The participant was suppressed when they discontinued DOVATO and transitioned to a DTG-based regimen (DTG + DRV/c). A baseline genotypic test demonstrated no NRTI or INSTI resistance.
‖One participant in the DOVATO arm demonstrated TAMs and M184V resistance but no integrase resistance. This participant switched to a DTG-based regimen (DTG + DRV/c) and was suppressed at the time of the switch. In the BIKTARVY arm, 1 participant demonstrated M184M/I and integrase resistance (G140G/S). The participant in the BIKTARVY arm was suppressed when they discontinued from the study, and they remained on BIKTARVY.
WEIGHT CHANGE DATA
Mean Change in Weight at Week 481
Clinical significance of these data is unknown.
ns=not significant.
There was no statistically significant difference between arms in mean change in weight from baseline.1
PASO DOBLE: The Largest Head-to-Head Clinical Trial of DOVATO vs BIKTARVY to Date¶
TRIAL DESIGN
A Phase 4, Randomized (1:1), Open-Label, Noninferiority Trial of DOVATO vs BIKTARVY2
Stratification by use of TAF-containing regimen at baseline and sex at birth.
PASO DOBLE is a multicenter study conducted in Spain.2
¶The other clinical trials comparing DOVATO vs BIKTARVY are DYAD (N=222) and RUMBA (N=134).1,3
Select Inclusion Criteria2
- Virologically suppressed ≥24 weeks
- On current ART containing >1 pill/day, or any STR containing at least one of the following: COBI booster, EFV, or TDF
- No evidence of previous viral failure
- No known or suspected resistance to study drugs
Select Exclusion Criteria2
- Previously treated with DTG or BIC
- Chronic hepatitis B
Primary Endpoint2
- Proportion of participants with plasma HIV-1 RNA ≥50 copies/mL at Week 48 in the ITT–E population (FDA Snapshot, 4% noninferiority margin)
Secondary Endpoints4
- Proportion of participants with plasma HIV-1 RNA <50 copies/mL at Weeks 48 and 96 in the ITT–E population (FDA Snapshot, -8% noninferiority margin)
- Absolute weight change at Week 48 and Week 96
- Proportion of participants with weight change >5% from baseline at Week 48 and Week 96
All participants had no prior exposure to DTG or BIC. 72% of patients were on an ART regimen without TAF prior to randomization2
BASELINE CHARACTERISTICS
PASO DOBLE Studied >500 Patients Who Had on Average ~11 Years on ART2
| Baseline Characteristics | DOVATO (n=277) |
BIKTARVY (n=276) |
|---|---|---|
| Age, years, median (IQR) | 50 (41-57) | 51 (39-58) |
| Sex, n (%) | ||
| Female | 74 (26.7%) | 73 (26.4%) |
| Ethnicity, n (%) | ||
| Caucasian | 201 (72.6%) | 201 (72.8%) |
| Latin | 66 (23.8%) | 67 (24.3%) |
| Black | 4 (1.4%) | 5 (1.8%) |
| CD4+ <350 cells/mm3, n (%) | 26 (9.4%) | 24 (8.7%) |
| Years on ART, years, median (IQR) | 11.7 (7.2-19.3) | 11.1 (7.0-19.2) |
| Duration of prior ART regimen, months, median (IQR) | 66.2 (43.5-97.0) | 62.8 (41.1-88.7) |
| Presence of TAF in previous ART, n (%) | 77 (27.8%) | 78 (28.3%) |
| Presence of TDF in previous ART, n (%) | 92 (33.2%) | 103 (37.3%) |
| Weight at baseline, kg, median (IQR)5 | 72.8 (63.4-83.3) | 72.8 (63.0-81.8) |
| BMI, kg/m2, median (IQR) | 25.1 (22.3-28.5) | 24.8 (22.2-28.2) |
| Overweight/ obese (BMI >25 kg/m2), n (%) | 143 (51.8%) | 134 (48.6%) |
Across both arms, patients were, on average, ~50 years of age and on ART for ~11 years2
EFFICACY
DOVATO Was Noninferior to BIKTARVY at 48 Weeks
Snapshot Outcomes at Week 48 in ITT–E Population2
At Week 48, 13 (4.7%) participants on DOVATO and 26 (9.4%) participants on BIKTARVY had no virologic data.
RESISTANCE
High Barrier to Resistance
0
(n=0/277)
cases of treatment-emergent resistance in the DOVATO arm
vs 0 (n=276) in the BIKTARVY arm at Week 482
Only participants meeting CVF criteria were tested for resistance (0 for DOVATO, 1 for BIKTARVY). Confirmed virologic failure was defined as HIV-1 RNA ≥50 copies/mL followed by a second consecutive HIV-1 RNA assessment ≥200 copies/mL at any point through Week 48.2
WEIGHT CHANGE DATA
At Week 48, DOVATO Participants Experienced Statistically Significantly Less Weight Gain vs Those on BIKTARVY
Adjusted Mean Weight Change2
Adjusted by baseline value, sex, presence of TAF in previous ART, age, and ethnicity.2
At Week 48, participants in the BIKTARVY arm gained more weight than DOVATO participants2
The clinical significance of these findings is unknown.
Change in weight from baseline at Week 48 for DOVATO was consistent with the TANGO study.5
Data from Week 48 was a prespecified secondary endpoint. Data from Weeks 6 and 24 were not specified endpoints.4
BIKTARVY Had Statistically Significantly More Participants Who Gained >5% of Their Baseline Weight vs DOVATO
Proportion of Participants With Weight Change >5% of Baseline2
The adjusted odds ratio# at Week 48 was 1.81 (95% CI; 1.19, 2.76; P=0.006) with fewer DOVATO participants gaining >5% of baseline weight.2
For the average participant in the study, 5% of body weight was ~8 lb (~3.26 kg)5
Weight gain >5% of baseline at Week 48 was a prespecified secondary endpoint. Data from Weeks 6 and 24 were not specified endpoints.4
#Adjusted by baseline value, sex, presence of TAF in previous ART, age, and ethnicity.2
DISCOVER 4 YEARS OF DOVATO DATA AMONG SUPPRESSED PATIENTS
ART=antiretroviral therapy; BIC=bictegravir; BMI=body mass index; CI=confidence interval; COBI=cobicistat; CVF=confirmed virologic failure; CVW=confirmed virologic withdrawal; DRV/c=darunavir/cobicistat; DTG=dolutegravir; EFV=efavirenz; HBV=hepatitis B virus; HCV=hepatitis C virus; INSTI=integrase strand transfer inhibitor; IQR=interquartile range; ITT–E=intent-to-treat–exposed; NRTI=nucleoside reverse transcriptase inhibitor; STR=single-tablet regimen; SVF=suspected virologic failure; TAF=tenofovir alafenamide; TAM=thymidine analogue mutation; TDF=tenofovir disoproxil fumarate.
References:
1. Rolle C-P, Castano J, Nguyen V, Hinestrosa F, DeJesus E. Efficacy, safety, and tolerability of switching from bictegravir/emtricitabine/tenofovir alafenamide to dolutegravir/lamivudine among adults with virologically suppressed HIV: the DYAD study. Open Forum Infect Dis. 2024;11(10):1-10. doi:10.1093/ofid/ofae560
2. Ryan P, et al. Non-inferior efficacy and less weight gain when switching to DTG/3TC than when switching to BIC/FTC/TAF in virologically suppressed people with HIV (PWH): the PASO-DOBLE (GeSIDA 11720) randomized clinical trial. Abstract presented at: AIDS 2024; July 22-26, 2024; Virtual and Munich, Germany. Oral abstract OAB3606LB.
3. Vandekerckhove L, Trypsteen W, Blomme E, et al. Impact of switch towards 3TC/dolutegravir on the intact and total HIV-1 viral reservoir in the RUMBA study. Presented at: HIV Drug Therapy Glasgow; October 23-26, 2022; Virtual and Glasgow, Scotland. Slides M042.
4. ClinicalTrials.gov. DTG/3TC vs. BIC/FTC/TAF maintenance therapy in people living with HIV: (PASO-DOBLE). NCT04884139. Updated August 25, 2023. Accessed July 19, 2024.
5. Data on file, ViiV Healthcare.
PMUS-DLLWCNT240066 October 2024
