Weekly Oral HIV Maintenance Therapy Matches Daily B/F/TAF
Key Takeaways
- Adults with HIV-1 already suppressed on daily B/F/TAF had similar week-48 viral suppression after switching to once-weekly oral ISL/LEN or continuing daily therapy.
- No participants assigned to weekly ISL/LEN and 0.3% of those continuing daily B/F/TAF had HIV-1 RNA of at least 50 copies/mL at week 48, and the prespecified noninferiority criterion was met.
- Discontinuation because of adverse events was infrequent in both groups, occurring in 2% with weekly ISL/LEN and 1.7% with daily B/F/TAF.
- Serious adverse events were uncommon in both groups, occurring in 5.3% with weekly ISL/LEN and 4.6% with daily B/F/TAF.
Investigators conducted a phase 3, double-blind, randomized, active-controlled, noninferiority trial in 12 countries among adults whose HIV-1 had been virologically suppressed for at least 6 months while receiving once-daily bictegravir-emtricitabine-tenofovir alafenamide (B/F/TAF). A total of 607 participants were randomized in a 1:1 ratio, with 304 assigned to once-weekly oral islatravir-lenacapavir (ISL/LEN) at 2 mg/300 mg and 303 continuing daily B/F/TAF during a planned 96-week treatment period with matched placebo for the alternative regimen. The primary endpoint was HIV-1 RNA of 50 copies per milliliter or higher at week 48 by the Food and Drug Administration-defined snapshot algorithm, with noninferiority set at a margin of 4 percentage points. The researchers also reported that 21% of participants were women, 31% were Black, 26% were Hispanic or Latine, and 15% were 65 years of age or older.
At week 48, HIV-1 RNA of 50 copies per milliliter or higher was reported in 0 participants in the weekly ISL/LEN group and 1 participant (0.3%) in the daily B/F/TAF group, for a between-group difference of -0.3 percentage points (95% confidence interval, -1.4 to 0.8), which met the prespecified noninferiority margin. In the Phase 3 trial of weekly oral islatravir-lenacapavir for HIV-1 treatment, HIV-1 RNA remained below 50 copies per milliliter in 284 of 304 participants (93.4%) receiving weekly therapy and 280 of 303 (92.4%) continuing daily therapy, a difference of 1.0 percentage point (95% confidence interval, -3.2 to 5.2). Mean CD4+ T-cell counts changed modestly in both groups at week 48.
These findings apply to maintenance after switching in adults already suppressed on B/F/TAF, not to treatment initiation or to people with unsuppressed HIV-1. Reportable evidence here is limited to the week-48 abstract summary within a planned 96-week trial, so longer-term efficacy and the fuller picture for resistance, adherence, subgroup effects, and safety are not yet available from this source.
According to the authors, among people with virologically suppressed HIV-1, once-weekly oral ISL/LEN was noninferior to once-daily B/F/TAF for maintaining viral load suppression.
Clinician Questions
Which patients with HIV-1 were represented in the weekly oral ISL/LEN maintenance trial?
The trial enrolled adults with HIV-1 whose viral load had already been suppressed for at least 6 months while they were receiving once-daily B/F/TAF, so the reported findings apply to switch-maintenance therapy in that population rather than to treatment initiation or to people with unsuppressed HIV-1.
How was the primary virologic endpoint defined?
The primary endpoint was the proportion of participants with HIV-1 RNA of 50 copies per milliliter or higher at week 48, determined by the Food and Drug Administration-defined snapshot algorithm.
What remains unanswered after the week-48 weekly oral ISL/LEN results?
The trial is planned for 96 weeks, but the reportable data here are limited to the week-48 abstract summary, and the abstract does not provide longer-term outcomes, subgroup analyses, resistance findings, adherence measures, or more detailed safety characterization.