Background:
While single-tablet regimens (STRs) are currently the global standard for HIV treatment, some people with HIV (PWH) take multi-tablet regimens (MTR) due to treatment resistance, intolerance or drug interactions. The combination of bictegravir (BIC), an integrase strand transfer inhibitor, and lenacapavir (LEN), a first-in-class capsid inhibitor, could simplify treatment in virologically suppressed (VS) PWH for whom STRs are not indicated. We report the Phase 2, 24-Week primary outcomes for BIC + LEN versus stable baseline regimen (SBR) in VS PWH on a complex regimen.
Methods:
ARTISTRY-1 (NCT05502341) is an ongoing, randomized, open-label, multicenter Phase 2/3 study. In Phase 2, 128 participants on SBR (≥6 months prior to screening) were randomized 2:2:1 to receive once-daily oral BIC 75 mg + LEN 25 mg, oral BIC 75 mg + LEN 50 mg or continue SBR. All participants receiving BIC + LEN received an oral loading dose of LEN 600 mg on Days 1 and 2 of treatment. The primary endpoint was the proportion of participants with HIV RNA ≥50 copies/mL (FDA Snapshot) at Week 24. Secondary endpoints included the proportion of participants with HIV RNA <50 copies/mL, change from baseline in CD4 cell count and the proportion of participants with treatment emergent adverse events (TEAEs) up to Week 24.
Results:
51 and 52 participants received BIC 75 mg + LEN 25 mg or BIC 75 mg + LEN 50 mg, respectively, and 25 continued SBR. At baseline, 19% of participants were female, 31% were Black and 16% were Hispanic or Latinx; median (Q1, Q3) age was 60 (56, 65) years and participants were taking a median (range) of 3 (2–9) tablets per day. Outcomes at Week 24 are shown in the Table. HIV-1 RNA was ≥50 copies/mL in 0/51 of participants in the BIC 75 mg + LEN 25 mg group, 1/52 (2%) in the BIC 75 mg + LEN 50 mg group (later suppressed to <50 copies/mL without regimen change) and 0/25 in the SBR group. CD4 counts were comparable in all groups. The most common TEAEs in the two BIC + LEN treatment groups up to Week 24 were diarrhea (7%), COVID-19 (6%) and constipation (5%). Drug-related TEAEs occurred in 18%, 6% and 0% of participants, respectively.
Conclusions:
BIC + LEN was highly effective in maintaining viral suppression in participants switching from an MTR, with similar safety profiles observed in the two BIC + LEN treatment groups. These data support the use of BIC and LEN in combination to simplify treatment in VS PWH who are receiving complex regimens. A BIC/LEN STR will be tested in the Phase 3 part of the study.
