A single once-daily pill combining two antiretrovirals simplifies HIV treatment, as demonstrated by a phase 3 trial

This international clinical trial shows that a new once-daily single-tablet combination of bictegravir and lenacapavir enables the safe simplification of treatment for people living with HIV who, despite maintaining viral suppression, rely on complex multi-tablet regimens due to previous resistance or other clinical constraints. In a particularly ageing population with a long treatment history, switching to this new tablet maintained virological control with efficacy comparable to that of complex regimens, without the emergence of new resistance and with a similar safety profile. However, the study demonstrated non-inferiority rather than superiority and was specifically designed to assess the feasibility of switching treatment, not to establish advantages in antiviral efficacy.

In addition to preserving HIV control, the new regimen was associated with greater patient satisfaction and improvements in metabolic parameters—key considerations for individuals with multiple comorbidities and polypharmacy. These findings are especially significant as they open, for the first time, the door to treatment simplification in patients previously considered difficult to simplify, a group for whom options were extremely limited. It should be noted, however, that these are medium-term data (limited to one year of follow-up), obtained in a carefully selected population not co-infected with hepatitis B virus. Longer-term data will therefore be needed to confirm the impact of this strategy and to define more precisely which clinical profiles stand to benefit most compared with other alternatives already available.

This study shows that in patients receiving complex antiretroviral regimens with good immunovirological outcomes, switching to a once-daily single tablet of a new combination (islatravir/lenacapavir) achieves equivalent results, with improved acceptance due to the much simpler regimen.

It is a high-quality study involving a very large number of patients, although it does not represent a major advance compared with other once-daily single-tablet options already available on the market. Nevertheless, these two agents are new, highly potent, and very well tolerated, and they allow for long-acting formulations—that is, a single tablet taken once a week. In this context, which is already under investigation, it is clear that being able to take just one tablet per week would represent a very substantial improvement for eligible patients.