The development of a new once-weekly HIV treatment regimen offers a significant step forward in managing Human Immunodeficiency Virus (HIV-1). Clinicians often face adherence challenges with the current daily oral medications. Therefore, a less frequent dosing schedule could profoundly impact long-term patient outcomes. This Phase 2, randomized, open-label study evaluated the efficacy and safety of once-weekly oral Islatravir (ISL) plus Lenacapavir (LEN) against the established daily standard, bictegravir, emtricitabine, and tenofovir alafenamide (B/F/TAF).
Trial Design and Primary Findings
The study enrolled adults who were virologically suppressed, meaning they had an HIV-1 RNA viral load of less than 50 copies/mL while on daily B/F/TAF for at least 24 weeks. A total of 104 participants were randomly assigned to either the once-weekly ISL (2 mg) plus LEN (300 mg) group or the continued daily B/F/TAF group. At the primary endpoint of week 24, both groups showed comparable, high rates of virologic suppression. For example, only one participant in the ISL+LEN group and none in the B/F/TAF group had a viral load of 50 copies/mL or more. Consequently, 94.2% of participants in both arms maintained a viral load of less than 50 copies/mL.
Sustained Efficacy with the Once-weekly HIV Treatment
The positive results were sustained through week 48, showing the long-term potential of the new regimen. At this later time point, 94.2% of ISL+LEN participants and 92.3% of B/F/TAF participants maintained an HIV-1 RNA viral load of less than 50 copies/mL. This difference was clinically insignificant. Furthermore, no participants in either group had a viral load of 50 copies/mL or more at week 48. These findings strongly suggest that switching to the weekly combination maintains virologic control effectively.
Safety Profile and Tolerability
Safety is a paramount concern for any new treatment. Thankfully, the once-weekly regimen was well-tolerated. Investigators observed that no serious adverse events (AEs) or AEs that were grade 3 or greater were related to the study drug in either arm. Two participants receiving ISL+LEN did discontinue treatment before week 24, but these discontinuations were attributed to AEs deemed unrelated to the study drug. Changes in CD4 T-cell and lymphocyte counts were also similar between the two groups from baseline to week 48. Moreover, clinicians saw no discontinuations due to decreases in these key immune markers. However, the open-label nature, modest sample size, and U.S.-only participants represent study limitations.
Frequently Asked Questions
Q1: What is the primary benefit of the once-weekly oral ISL+LEN regimen?
The primary benefit is addressing adherence challenges associated with daily medication. A less frequent, once-weekly dosing schedule can significantly simplify the treatment regimen for patients with HIV-1, potentially improving long-term success rates.
Q2: How does the efficacy of weekly ISL+LEN compare to the daily standard B/F/TAF?
The study demonstrated that the weekly ISL+LEN regimen maintained high rates of virologic suppression that were comparable to the daily B/F/TAF regimen through week 48. At week 24, both groups had 94.2% of participants with an HIV-1 RNA viral load of less than 50 copies/mL.
Q3: Were there any major safety concerns with the once-weekly treatment?
No. The study reported that no serious adverse events or adverse events of grade 3 or greater were related to the treatment in the ISL+LEN group or the B/F/TAF group.
References
- Colson AE et al. Once-Weekly Oral Islatravir Plus Lenacapavir Versus Daily Oral Bictegravir, Emtricitabine, and Tenofovir Alafenamide in Persons With HIV-1 : A Phase 2 Randomized Study. Ann Intern Med. 2025 Dec 23. doi: 10.7326/ANNALS-25-01939. PMID: 41429026.
- Rathbun, A., & Mahto, A. A Review of Emerging Long-Acting Agents for HIV Treatment and Prevention. Infectious Disease Clinics of North America. 22 Dec 2024.
- Clinical News Wire. Phase 2 Trial Confirms Efficacy and Safety of Novel Once-Weekly Oral HIV Regimen. MedPage Today. 15 Jan 2025.