PASO DOBLE is the largest head-to-head, phase 4 randomized clinical trial comparing DTG/3TC and BIC/FTC/TAF in patients with HIV.
ViiV Healthcare announced positive data demonstrating 2-drug regimen dolutegravir/lamivudine (DTG/3TC [Dovato]) can be used as an effective switch regimen for the 3-drug regimen bictegravir/emtricitabine/tenofovir alafenamide fumarate (BIC/FTC/TAF [Biktarvy]) for the treatment of HIV-1 in individuals who are virologically suppressed and who could benefit from treatment optimization, the company announced in a release.1 Additionally, DTG/3TC was shown to cause significantly less weight gain than BIC/FTC/TAF.
3D rendering of HIV virus / artegorov3@gmail - stock.adobe.com
PASO DOBLE (NCT04884139) is the largest head-to-head, phase 4 randomized clinical trial comparing DTG/3TC and BIC/FTC/TAF in the patient population.
About PASO DOBLE
Trial Name: DTG/3TC vs. BIC/FTC/TAF Maintenance Therapy in People Living With HIV: (PASO-DOBLE)
Clinicaltrials.gov Identifier: NCT04884139
Sponsor: Fundacion SEIMC-GESIDA
Summary: This trial is a phase IV, open-label, randomized multicentre clinical trial evaluating the efficacy of DTG/3TC versus BIC/FTC/TAF for the maintenance of virological suppression in HIV patients.
“The results from PASO DOBLE show that Dovato demonstrated non-inferior efficacy compared to Biktarvy, and that the average weight gain for trial participants taking DTG/3TC was significantly lower than those taking BIC/FTC/TAF over the course of the year,” said Harmony P. Garges, MD, MPH, chief medical officer at ViiV Healthcare, in the release.1 “This is a meaningful outcome, as treatment-related weight gain is an important topic for many people living with HIV. At ViiV Healthcare we’re dedicated to bringing innovative HIV treatments to people living with HIV that are not only safe and effective, but also address their specific needs beyond viral suppression.”
The PASO DOBLE clinical trial recruited 553 individuals living with HIV and who were virally suppressed. Patients switched treatment to either DTG/3TC (n=277) or BIC/FTC/TAF (n=276) as a once-daily pill. The study population included individuals who were on therapy that could be optimized, such as multiple tablet regimens, or those containing pharmacokinetic boosting agents or drugs with cumulative toxicity, such as efavirenz or tenofovir disoproxil fumarate.
The primary endpoint was met when DTG/3TC showed non-inferior efficacy compared to BIC/FTC/TAF in suppressing viral load to 50 copies/mL or below after 48 weeks, using the FDA snapshot and a 4% non-inferiority margin in the exposed intention-to-treat population.
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Ultimately, investigators found that at 48 weeks, DTG/3TC was non-inferior to BIC/FTC/TAF (risk difference between DTG/3TC [2.2%] minus BIC/FTC/TAF [0.7%] of 1.4%, 95% CI -0.5 to 3.4). Through week 48, protocol-defined confirmed virological failure (HIV-1 RNA ≥50 c/mL followed by a second consecutive HIV-1 RNA assessment ≥200 c/mL) occurred in 1 participant from the BIC/FTC/TAF arm and no participants in the DTG/3TC arm.
In addition to non-inferior efficacy, the DTG/3TC regimen also showed less weight gain compared to BIC/FTC/TAF through 48 weeks. On average, participants who switched to BIC/FTC/TAF gained 1.81 kilograms (95% CI 1.28-2.34) compared to 0.89 kilograms (95% CI 0.37-1.41) for those who switched to DTG/3TC, translating to nearly a kilogram worth of difference (95% CI 0.17-1.66). Further, the proportion of participants with weight gain exceeding 5% at week 48 was significantly higher at 29.9% for BIC/FTC/TAF compared to 20% for DTG/3TC (95% CI 1.19-2.76).
A higher percentage of participants gained more than 5% of their body weight when taking BIC/FTC/TAF compared to DTG/3TC. This difference was more pronounced among those switching from a regimen with abacavir (30.6% BIC/FTC/TAF vs 21.1% DTG/3TC) and even higher among those switching from a regimen with TDF (40.7% BIC/FTC/TAF vs 19.5% DTG/3TC).
Treatment-related weight gain is a significant concern for many people living with HIV for several reasons. Weight gain can be reason for people to stop taking their medication, which can lead to treatment failure and drug resistance. Additionally, it can increase the risk of developing serious health conditions such as heart disease and diabetes.3 The current study offers critical insights to optimize patient outcomes.
“The HIV treatment regimens that are commonly prescribed today are all highly effective, which makes it critical that we study the impact of these therapies beyond just viral suppression,” concluded Esteban Martínez, MD, PhD, chief executive investigator on PASO DOBLE and senior consultant in infectious diseases at Hospital Clínic of Barcelona, Spain, in the release.1 “The results from PASO DOBLE show Dovato, a 2-drug regimen, not just demonstrated the same efficacy as a 3-drug regimen, but also showed less weight gain compared to BIC/FTC/TAF through 48 weeks.”
Findings from PASO DOBLE, sponsored by the SEIMC-GeSIDA Foundation, will be announced at the 25th International AIDS Conference in Munich, Germany.3
READ MORE: HIV Resource Center
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