Bictegravir vs Darunavir in Advanced HIV: Results from the LAPTOP Trial

At CROI 2025, Georg Behrens, MD, PhD, professor for T-Cell Immunology at Hannover Medical School, discussed the findings from the LAPTOP trial, a multi-center, European, open-label study that compared bictegravir (BIC) with darunavir (DRV) in therapy-naïve individuals with advanced HIV disease. This trial aimed to evaluate the efficacy and safety of an integrase inhibitor (INI)-based regimen versus a boosted protease inhibitor (PI)-based regimen in individuals with high viral loads and low CD4 counts, a population often underrepresented in clinical trials.

The LAPTOP trial randomized nearly 450 participants across seven European countries to receive either BIC (combined with tenofovir alafenamide [TAF] and emtricitabine [FTC]) or DRV (with cobicistat, FTC, and TAF) for 48 weeks. The primary endpoint was time to failure, which was defined as the first occurrence of virological failure or specific clinical events.

The results demonstrated that BIC/TAF was superior to DRV-based therapy in achieving the primary composite endpoint. Participants in the BIC group showed a higher percentage of HIV RNA levels <50 copies/mL and experienced faster CD4 recovery. Additionally, fewer participants receiving BIC/TAF failed to achieve virological suppression compared to those on the PI-based regimen.

Behrens noted, "The challenge is that patients with advanced HIV disease are very often hospitalized and seek care for severe diseases. They are often excluded from other registrational trials because they have very low CD4 counts, numerous comorbidities, and opportunistic infections."

The inclusion of therapy-naïve individuals with advanced HIV disease presented several challenges in the trial. Participants in this group typically have severely compromised immune systems, with CD4 counts below 40 cells per microliter, and often require hospitalization for treatment of opportunistic infections. Behrens emphasized the difficulty in recruiting this population, which has often been underrepresented in clinical trials due to the complexity of their condition.

"These patients are very vulnerable. The diagnosis is made only a few days earlier, and they are often in critical care," Behrens explained. "It's a vulnerable time, and so recruiting them for a study like this is challenging."

The study also aimed to answer clinically relevant questions for this group, including concerns about drug-drug interactions and the risk of immune reconstitution inflammatory syndrome (IRIS). By incorporating clinical endpoints, the LAPTOP trial went beyond measuring viral suppression and assessed the real-world effectiveness of the two treatment regimens.

Bictegravir-based therapy was shown to have better virological outcomes and a faster immune recovery compared to darunavir-based therapy. Behrens emphasized that INIs like bictegravir, with their high genetic barrier and known safety profiles, are expected to become a central part of HIV treatment.

"Bictegravir-based therapy was non-inferior to darunavir-based therapy, but it showed better virological suppression and faster immune recovery," he said. "This suggests that integrase inhibitors may be a more effective and safer treatment option for therapy-naïve individuals with advanced HIV."

Despite the encouraging results, Behrens acknowledged that the study’s follow-up period was limited to 48 weeks, and the long-term safety and efficacy of both regimens remain to be fully explored. "We need long-term follow-up to better understand how these treatments perform over time and in more diverse populations."

"In the long run, if resistance mutations against integrase inhibitors develop due to their widespread use, protease inhibitors might once again become a viable treatment option," he said. "This is something we must plan for, not just for the next five years, but for the next 10 to 20 years."

Looking ahead, Behrens and his team are planning to explore the mechanisms underlying the faster immune recovery seen in the bictegravir arm. "We plan to reanalyze samples from these patients using more advanced technologies to better understand why the viral load decline in the bictegravir arm is faster and whether this translates into quicker resolution of inflammation," Behrens said.

While there are no plans for further follow-up of the LAPTOP study, the research team is committed to continuing their investigation into the long-term safety and efficacy of both regimens.

Reference

Behrens G, et. al. Bictegravir vs Darunavir in Therapy-Naïve Individuals With Advanced HIV: A Non-Inferiority Trial. Presented at: CROI 2025; March 9-12, 2025; San Francisco, California.