OBJECTIVES:: Coronavirus disease 2019 (COVID-19) vaccination is reportedly efficient in people with HIV (PWH) but vaccine trials included participants with normal CD4 T-cell counts. We analyzed seroconversion rates and antibody titers following two-dose vaccination in PWH with impaired CD4 T-cell counts. METHODS:: We collected retrospective postvaccination SARS-COV-2 serology results available in a university hospital for PWH vaccinated between March and September, 2021 who were tested for antispike antibodies from 8 to 150 days following dose 2. Antibody titers were compared in PWH with CD4 T-cell count less than 200 cells/μl, 200 < CD4 T-cell counts < 500 cells/μl and CD4 T-cell count greater than 500 cells/μl at vaccination. RESULTS:: One hundred and five PWH were included: n = 54 in the CD4 T-cell count less than 500 cells/μl group (n = 18 with CD4 <200 cells/μl, n = 36 with 200 < CD4 < 500 cells/μl) and 51 in the CD4 T-cell count greater than 500 cells/μl group. They received two doses of BNT162b2 (75%), mRNA-1273 (8.5%), or ChAdOx1 nCoV-19 (16.5%). The median time from vaccine dose 2 to serology was consistent across all groups (73 days, interquartile range [29–97], P = 0.14). Seroconversion rates were 100% in the CD4 T-cell count greater than 500 cells/μl group but 89% in participants with CD4 T-cell counts less than 500 cells/μl (22 and 5.5% seronegative in the CD4 T-cell counts <200 cells/μl and 200 < CD4 < 500 cells/μl groups, respectively). Median antibody titers were 623.8 BAU/ml [262.2–2288] in the CD4 greater than 500 cells/μl group versus 334.3 BAU/ml [69.9–933.9] in the CD4 less than 500 cells/μl group (P = 0.003). They were lowest in the CD4 less than 200 cells/μl group: 247.9 BAU/ml [5.88–434.9] (P = 0.0017) with only 44% achieving antibody titers above the putative protection threshold of 260 BAU/ml. CONCLUSION:: PWH with CD4 T-cell counts less than 500 cells/μl and notably less than 200 cells/μl had significantly lower seroconversion rates and antispike antibody titers compared with PWH with CD4 T-cell counts greater than 500 cells/μl, warranting the consideration of targeted vaccine strategies in this fragile population.