Estudio de combinación semanal
A once-weekly oral combination of islatravir plus lenacapavir (Sunlenca) for HIV maintained similarly high rates of virologic suppression compared with standard daily oral treatment in an open-label phase II trial.
In 104 virologically suppressed adults with HIV-1 on the daily oral regimen of bictegravir, emtricitabine, and tenofovir alafenamide, just one patient randomized to receive once-weekly islatravir-lenacapavir had an HIV-1 RNA viral load of 50 copies/mL or greater after 24 weeks compared with none of those assigned to continue on the daily oral regimen (1.9% difference, 95% CI -5.2 to 10.5).
By week 48, 94.2% of the weekly group and 92.3% of the daily group had viral loads below 50 copies/mL, reported researchers led by Amy Colson, MD, of Community Resource Initiative in Boston.
Aderencia a la medicación
Furthermore, the proportion of patients with at least a 95% medication adherence rate was greater in the weekly group (98%) than in the daily group (86.3%), they detailed in Annals of Internal Medicine.
“These results provide reassurance that the transition from daily to once-weekly dosing does not have an adverse effect on adherence and offers a favorable outlook for long-acting treatment strategies,” Colson and colleagues wrote. “Offering a range of treatment options with differing administration routes and dosing intervals remains important to meet the diverse needs of persons with HIV-1 and minimize barriers to antiretroviral therapy adherence.”
Desafíos de tratamientos diarios
Once-daily oral antiretroviral treatments for HIV-1 infection are effective as standard care, but the daily requirement can create medication compliance challenges.
“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 told MedPage Today. “Addressing these day-to-day stressors can lead to meaningful improvement in quality of life, which is particularly important when managing a medical condition that requires lifelong treatment.”
Mecanismos de acción
Islatravir is an investigational nucleoside reverse transcriptase translocation inhibitor. Lenacapavir is a capsid inhibitor that’s approved for use as either an oral or subcutaneous treatment in combination with other antiretrovirals for multidrug resistant HIV. (Lenacapavir is also approved as a twice-yearly injection for pre-exposure prophylaxis in those at risk of HIV, under the trade name of Yeztugo).
Efecto sobre los linfocitos
“This phase II trial provides reassuring data regarding the impact of islatravir on CD4 cells,” Colson said. In earlier studies, higher doses were linked with decreases in CD4+ T-cell and lymphocyte counts. The study used a relatively low dose of islatravir, at 2 mg per week, and CD4+ counts remained stable in both treatment groups through week 48.
Detalles del estudio
The phase II study from Colson and colleagues took place across 44 U.S. healthcare centers from February 2023 to July 2024 and included patients with HIV-1 who were already receiving daily oral treatment with bictegravir, emtricitabine, and tenofovir alafenamide. To enroll, participants had an HIV-1 RNA viral load less than 50 copies/mL for at least 24 weeks, a CD4+ T-cell count of at least 0.35 × 109 cells/L, and a lymphocyte count of at least 0.9 × 109 cells/L.
Participants were randomized in an open-label fashion to 48 weeks of either the once-weekly oral combination of islatravir (2 mg) and lenacapavir (300 mg) or to remain on their same daily oral regimen (bictegravir, emtricitabine, and tenofovir alafenamide).
The average age was 44 years, 18.3% were assigned female at birth, 50% were non-white, and 28.8% of the participants were of Hispanic or Latine ethnicity. The average CD4+ T-cell count at baseline was 0.786 × 109 cells/L.
Resultados y efectos adversos
The study’s primary endpoint was the proportion of participants who had an HIV-1 RNA viral load of at least 50 copies/mL at 24 weeks of treatment. Secondary endpoints included the proportions with viral loads at or below 50 copies/mL at weeks 12, 24, and 48; treatment-related adverse events (AEs) leading to discontinuation; and CD4+ T-cell count changes from baseline to weeks 12, 24, and 48.
The percentage of participants reporting AEs through week 48 was slightly higher in the weekly group (80.8%) than in the daily group (76.9%). Treatment-related AEs happened in 19.2% of the weekly group compared with 5.8% of the daily group. Grade 3/4 AEs were more likely in the weekly group than in the daily group (7.7% vs 1.9%), as were serious AEs (5.8% vs 0%).
Although two people in the weekly group had AEs that led to study discontinuation, none was considered treatment-related. No one in the daily group dropped out of the study because of an AE.
Mean change by week 48 from baseline CD4+ T-cell count was -0.012 × 109 cells/L in the weekly group and -0.029 × 109 cells/L in the daily group.
Estudios futuros
The islatravir-lenacapavir combination is now in phase III multinational studies.
Limitaciones del estudio
Limitations of the current study included its open-label design, which could have influenced how participants report their subjective AEs.
Nota de descargo de responsabilidad
Este artículo tiene fines informativos y no sustituye la opinión médica profesional. Siempre consulte a un médico o profesional de salud calificado sobre cualquier duda que tenga respecto a una condición médica.
Fuente: https://www.medpagetoday.com/infectiousdisease/hivaids/119149
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