Gilead discontinued a Phase 2/3 trial of its long-acting oral HIV regimen after the FDA clinical hold remained in place. The program, Wonders-2, tested a combination of GS-1720 (integrase strand transfer inhibitor) and GS-4182 (capsid inhibitor) against Biktarvy. While some immune cell measures later returned to baseline for participants, the study was still terminated for “discontinued safety follow up,” effectively ending the trial. The FDA’s hold on the Wonders-1 sister study and related clinical testing remains intact. Gilead said it continues to work with study investigators to transition participants to standard of care options. The company is also working on long-acting integration strategies that build from lenacapavir’s regulatory pathway, including the earlier approval of Yeztugo (lenacapavir) and efforts to pair it with additional mechanisms. The move underscores how safety signals and clinical-hold constraints can derail multi-drug platform strategies even when short-term biomarker normalization is observed.