Once-Weekly Oral HIV Therapy Shows Promise in Phase 2 Trial, Maintaining Viral Suppression Through 48 Weeks
核心洞察
A phase 2 trial demonstrated that once-weekly oral islatravir plus lenacapavir maintained high rates of HIV viral suppression through 48 weeks in adults already suppressed on daily therapy.
The experimental weekly regimen achieved 94.2% viral suppression at week 24 and maintained efficacy through week 48, with no treatment-emergent resistance detected.
Safety profile was favorable with no treatment-related grade 3 or higher adverse events, and CD4+ T-cell counts remained stable throughout the study period.
A once-weekly oral combination of islatravir and lenacapavir maintained high rates of virologic suppression through 48 weeks in adults with HIV-1 (搜索), according to results from a phase 2, randomized, open-label, active-controlled study conducted across 44 US sites. The findings suggest a potential breakthrough in HIV treatment that could address adherence challenges associated with daily antiretroviral therapy.
Study Design and Population
The randomized trial enrolled 104 adults with HIV-1 (搜索) infection who had achieved virologic suppression (HIV-1 RNA < 50 copies/ml) for at least 24 weeks on treatment with bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF). Participants were randomized in a 1:1 ratio to either switch to weekly islatravir 2 mg plus lenacapavir 300 mg or remain on their daily BIC/FTC/TAF regimen.
The primary endpoint was the proportion of participants with HIV RNA greater than or equal to 50 copies/ml at week 24. At week 48, all participants were given the opportunity to enter an extension phase and receive the experimental weekly regimen.
Efficacy Results
The once-weekly combination demonstrated robust efficacy comparable to daily therapy. At week 24, one participant in the islatravir plus lenacapavir group and no participants in the BIC/FTC/TAF group had HIV-1 (搜索) RNA viral load of 50 copies/mL or more. In both treatment groups, 94.2% of participants maintained an HIV-1 RNA viral load of less than 50 copies/mL at week 24.
High efficacy was sustained through week 48, with no participants in either group having HIV-1 (搜索) RNA viral load of 50 copies/mL or more. Viral suppression was maintained by 94.2% in the islatravir plus lenacapavir group and 92.3% in the BIC/FTC/TAF group.
The single participant in the experimental group with detectable viremia at week 24 had entered the study with viremia (HIV-1 (搜索) RNA 251 copies/mL) and demonstrated detectable HIV-1 RNA at week 24 (HIV-1 RNA <100 copies/mL) but resuppressed by week 30 on continued treatment. Based on self-report, pill counts, and pharmacokinetic parameters, this individual appeared to take the medication correctly.
Resistance Profile
No emergent resistance to islatravir or lenacapavir was detected in the study by genotypic or phenotypic analysis, including in the individual who had low-level viremia at week 24 and then re-suppressed on the regimen. This finding suggests a low risk of treatment-emergent resistance with the once-weekly combination.
Safety and Tolerability
The safety profile was favorable, with no treatment-related grade 3, grade 4, or serious adverse events in either group. Adverse events related to islatravir plus lenacapavir were all grade 1 or grade 2 and occurred in 19% of participants versus 6% in the BIC/FTC/TAF group. The most common treatment-related adverse events in the experimental group were diarrhea and dry mouth, each occurring in 2 participants.
Importantly, CD4+ T-cell counts remained stable in both treatment groups through week 48. The mean change from baseline to week 48 in CD4+ T-cell count was −12 (SD, 214.7) cells/μL in the islatravir plus lenacapavir group and −29 (SD, 186.1) cells/μL in the BIC/FTC/TAF group. This stability is particularly significant given that higher doses of islatravir in prior studies were associated with decreases in CD4+ T-cell and lymphocyte counts.
Adherence Outcomes
Adherence by pill count was high in both arms, with a median adherence of 100% in the islatravir plus lenacapavir group and 98.8% in the BIC/FTC/TAF group through week 48. The proportion of participants achieving adherence rates of at least 95% was higher with once-weekly treatment than with daily therapy. No participants discontinued treatment due to lack of efficacy, and no clinically meaningful differences were observed between groups in weight or body mass index over the study period.
Clinical Implications and Future Directions
According to Dr. Amy Colson, medical director of the Zinberg Clinic (搜索) at Cambridge Health Alliance and research director at Community Resource Initiative (搜索), the results are encouraging for the HIV community. "If the robust efficacy and safety data are confirmed in the ongoing phase 3 ISLEND studies, islatravir plus lenacapavir could become the first once-weekly treatment option for people living with HIV-1 (搜索) infection," she noted.
The potential clinical impact extends beyond efficacy metrics. "Clinicians who care for people with HIV recognize how daily pill taking can generate adherence-anxiety, raise privacy concerns, and serve as a frequent reminder of HIV status," Colson explained. "Addressing these day-to-day stressors could lead to meaningful improvement in quality-of-life which is particularly important when we are dealing with a medical condition which requires lifelong treatment."
Study Limitations
Key limitations include the small sample size, restriction to US sites only, and the open-label design. As in all open-label studies, knowledge of treatment assignment could bias the reporting of adverse events. The findings are most applicable to adults with HIV-1 (搜索) infection, virologic suppression, and no history of antiretroviral treatment failure.
The ongoing phase 3 studies are larger and will evaluate the combination in a global population, providing robust safety, efficacy, and patient-reported-outcomes data from diverse regions to make the results more generalizable to the global community of people living with HIV.