The increased risk of severe COVID-19 breakthrough illness for PWH with moderate immune suppression (ie, CD4 cell count 200-349 cells/μL)27 (1) suggests that the recommendation for additional primary series vaccination doses should be expanded to PWH with moderate immune suppression, (2) supports the current recommendation of a first booster, and (3) suggests counseling on risk-reduction strategies among those with moderate immune suppression. This evidence concerns the gene CD4 and COVID-19.