Clinical Takeaways From ViiV’s PASO DOBLE and CLARITY Studies

Prior to the start of IDWeek 2025, ViiV Healthcare announced new 96-week results from their phase 4 PASO DOBLE (GeSIDA 11720) study. The findings showed that the 2-treatment regimen dolutegravir/lamivudine (DTG/3TC; Dovato) maintains virological suppression as effectively as the 3-treatment regimen bictegravir/emtricitabine/tenofovir alafenamide fumarate (BIC/FTC/TAF; Biktarvy) in adults with HIV.¹

The study met its primary end point, with DTG/3TC demonstrating sustained noninferior efficacy vs BIC/FTC/TAF based on the proportion of participants with HIV-1 RNA ≥ 50 copies/mL at 96 weeks using the FDA snapshot and a 4% noninferiority margin in the exposed intention-to-treat population.¹

“We've already seen the week 48 data, where we showed noninferior efficacy for Dovato vs Biktarvy. And we've now also shown that at 96 weeks, with very good efficacy rates for both treatment arms, very low rates of biologic failure, and no resistance development,” Jean van Wyk, MBChB, MFPM, chief medical officer at ViiV Healthcare, told Contagion at IDWeek.

The secondary end point of the study was assessing weight gain.

“What we see at week 96 is that there's now a significant difference in weight gain in favor of the Dovato arm—so over 3 lb of additional weight gain with Biktarvy,” van Wyk said. “We, of course, know that increased weight gain can have adverse cardiometabolic effects over time. It's interesting that half of people in the US who are living with HIV are above 50 years old, so they also use lots of other medications. They already have other comorbidities. So we have to think about long-term health—in this case, metabolic health—and if we can avoid it by adding any additional pressure on the cardiovascular system, that could be a good thing.”

CLARITY Study

Separately, in the lead-up to IDWeek, ViiV presented data from its phase 1 CLARITY study that provided the first direct comparison of the acceptability and tolerability of single-dose cabotegravir (CAB) and lenacapavir (LEN) long-acting (LA) injections in HIV-negative adults. The company reported that 69% of participants rated CAB injections as “totally or very acceptable” compared with 48% for LEN. Additionally, 90% of participants and 86% of health care providers (HCPs) preferred CAB over LEN after receiving single doses of both injectables.²

“CLARITY was designed where we gave one dose of each of those 2 drugs to healthy volunteers. We included 63 individuals in the trial. They got one drug on day 1 and then the other drug on day 15,” van Wyk said.

Participant and Provider Preferences:

• Participants: A total of 90% (54 of 60) preferred CAB LA; 10% (6 of 60) preferred LEN.
• HCPs: A total of 86% (6 of 7) preferred CAB LA; 14% (1 of 7) preferred LEN.²

Top Reasons for CAB Preference:

• Less pain during injection (74%)
• Less postinjection soreness (61%)
• Shorter duration of injection-site swelling (57%)
• Smaller injection-site nodules (56%)²

Participants who preferred LEN cited less soreness after injection and smaller or shorter-lasting swelling.

In terms of the modality itself, van Wyk believes LA injectables will play a vital role. “We believe that long-acting injectables really are an integral part in the future of HIV therapy as well as prevention,” he said.

References
1.ViiV Healthcare announces 96-week data reaffirming Dovato is as effective as Biktarvy in maintaining virological suppression of HIV-1 with significantly less weight gain. Press release. ViiV Healthcare. October 17, 2025. Accessed October 19, 2025.
https://www.businesswire.com/news/home/20251015024690/en/ViiV-Healthcare-announces-96-week-data-reaffirming-Dovato-is-as-effective-as-Biktarvy-in-maintaining-virological-suppression-of-HIV-1-with-significantly-less-weight-gain
2. ViiV Healthcare’s CLARITY study shows long-acting cabotegravir more acceptable than lenacapavir injections after a single dose, with 90% preferring cabotegravir. Press release. GSK. October 15, 2025. Accessed October 15, 2025.
https://www.gsk.com/en-gb/media/press-releases/viiv-healthcare-s-clarity-study-shows-long-acting-cabotegravir-more-acceptable-than-lenacapavir-injections-after-a-single-dose-with-90-preferring-cabotegravir/