The adjusted regression model showed that CD4+ T cell count (<200 vs. ≥500, β = −0.279, p = 0.018), HIV viral load (≥200–<5000 vs. <200, β = −0.35, p = 0.002), and days between second vaccination dose date and serology sample collection date (β = −0.003, p < 0.001) predicted Box–Cox-transformed SARS-CoV-2 spike (trimer) total Ig titers in PLWH who received two doses of a COVID-19 vaccine (Table 3). This evidence concerns the gene CD4 and COVID-19.