Dovato Offers Similar Efficacy, Less Weight Gain to Biktarvy in Head-to-Head Trial

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.

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.

“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.

READ MORE: Digital Health Tools Could Increase PrEP Uptake Among Young Individuals At-Risk For HIV

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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References

1. ViiV Healthcare announces positive data demonstrating 2-drug regimen Dovato is as effective as 3-drug regimen Biktarvy for maintenance therapy of HIV-1. News release. Businesswire. July 23, 2024. Accessed July 24, 2024. https://www.businesswire.com/news/home/20240719271594/en/ViiV-Healthcare-announces-positive-data-demonstrating-2-drug-regimen-Dovato-is-as-effective-as-3-drug-regimen-Biktarvy-for-maintenance-therapy-of-HIV-1

2. Elmer PJ, Brown JB, Nichols GA, Oster G. Effects of weight gain on medical care costs. Int J Obes Relat Metab Disord. 2004;28(11):1365-1373. doi:10.1038/sj.ijo.0802774

3. ViiV Healthcare to announce data form largest head-to-head randomized clinical trial for 2-drug regimen Dovato against 3-drug regimen Biktarvy at AIDS 2024. News release. ViiV Healthcare. July 15, 2024. Accessed July 24, 2024. https://viivhealthcare.com/hiv-news-and-media/news/press-releases/2024/july/viiv-healthcare-to-announce-data-from-largest-head-to-head-randomised/