Lenacapavir, a twice-yearly injectable, suppresses viral load in people with highly resistant virus, and it also shows promise for previously untreated people. In the Phase II/III CAPELLA trial, 36 adults with resistance to multiple antiretrovirals were first randomized to add oral lenacapavir or a placebo to their current failing regimen for two weeks; 88% and 17%, respectively, had at least a half-log reduction in viral load. Next, they received lenacapavir injections every six months plus an optimized background regimen. Interim results at 26 weeks showed that 81% had a viral load below 50. This was accompanied by an average gain of 81 CD4 cells. The Phase II CALIBRATE trial enrolled 182 previously untreated participants who were randomized to receive injectable or oral lenacapavir plus two other antiretrovirals or a standard three-drug regimen for 28 weeks. At that point, approximately 94% of lenacapavir recipients had an undetectable viral load. Going forward, they will receive lenacapavir injections every six months with just one other drug.