Nearly a year after a safety signal prompted the FDA to pause five HIV studies run by Gilead Sciences, the biopharma has terminated one affected programme: the Phase II/III WONDERS-2 trial. The study had been assessing a once-weekly oral regimen comprising GS-1720, an integrase strand transfer inhibitor, and GS-4182, a prodrug of capsid inhibitor lenacapavir, approved as Yeztugo as an HIV preventative and marketed as Sunlenca to treat multi-drug-resistant HIV.WONDERS-2 was comparing the combo against Gilead's megablockbuster HIV drug Biktarvy (bictegravir/emtricitabine/tenofovir alafenamide) in treatment-naive HIV patients, while a similar study, WONDERS-1, is testing the duo in patients who are virologically suppressed (see – Vital Signs: Gilead's fastest growing drugs and Vital Signs: Best selling drugs of 2025).According to ClinicalTrials.gov, while WONDERS-2 has ended, WONDERS-1 remains active. The FDA had placed a clinical hold on both trials in June after a subset of patients who received GS-1720 and GS-4182 experienced decreases in CD4-positive T-cell and absolute lymphocyte counts, which could indicate weakened immune systems. Three other Phase I studies evaluating the experimental HIV treatments alone, or in combination with each other, were also paused. "Following consultation with the FDA, Gilead has discontinued safety follow up in GS US 695 7156 (WONDERS-2), effectively terminating the study," a Gilead spokesperson told FirstWord. "All participants currently enrolled have CD4 and absolute lymphocyte count levels that have returned to baseline or are within normal ranges."Despite the setback, Gilead's late-stage HIV pipeline has other shots on goal. The biopharma is running the Phase III ARTISTRY-1 and ARTISTRY-2 trials, which are testing whether virologically suppressed patients can be switched to a fixed-dose tablet of bictegravir and lenacapavir without losing viral control. The former study enrolled close to 700 patients who were taking up to 11 daily antiretroviral pills, and the latter recruited nearly 600 patients on Biktarvy.