CD4 and infection: Finally, breakthrough risk varied by calendar period, aligning with the surge of infections and Omicron variant.27 Through these variations over time, the cumulative incidence of breakthroughs was higher among PWH vs PWoH regardless of CD4 count, suggesting residual immune function abnormalities (despite CD4 count recovery) results in an increased risk of breakthroughs for all PWH, not only those with advanced HIV disease or unsuppressed HIV RNA.