SARS-CoV-2 spike (trimer) total Ig seropositive rates among PLWH who received two doses of a COVID-19 vaccine were 42.9% in those with CD4+ T cell counts < 200 cells/μL, 77.4% in those with ≥200–<500 cells/μL, and 86.0% in those with ≥500 cells/μL (p < 0.001). Here, CD4 is linked to COVID-19.