People living with HIV (PLWH) are susceptible to severe COVID‐19 infection and hence this fragile population has prioritised vaccination. This systematic review and meta‐analysis aimed to assess the humoral immune response after receiving two doses schedule of COVID‐19 mRNA vaccinations in this high‐risk population. A systematic electronic search on the PubMed database and manual searches were performed for relevant articles until 30 Sep 2022. Two outcomes of interest were seroconversion rates and anti‐spike receptor binding domain (anti‐S‐RBD) antibody titres at the median time of 14–35 days following two‐dose vaccination among PLWH. Nineteen cohorts and one cross‐sectional study were eligible for inclusion in this study. The pooled estimate of seroconversion rate after receiving two doses of mRNA vaccination schedule were 98.4% and 75.2% among PLWH with CD4>500 cells/mm3 and CD4<200 cells/mm3, respectively. Compared with controls, PLWH with CD4>500 cells/mm3 had a 51% likelihood of having positive anti‐Spike‐RBD immunoglobulin G (IgG) (OR: 0.509, 95% CI: 0.228, 1.133, p = 0.098) post‐vaccination and this value was only 1.4% (OR: 0.014, 95% CI: 0.002, 0.078, p = 0.000) for PLWH with CD4<200 cells/mm3. There was no significant difference in titres of antibodies on 14–35 days post‐vaccination between PLWH with CD4>500 cells/mm3 and healthy controls (p = 0.06). The pooled median of anti‐S‐RBD IgG values were 1461.93 binding antibody units (BAU)/ml and 457.41 BAU/ml in PLWH with CD4>500 cells/mm3 and CD4<200 cells/mm3, respectively. According to these findings, vaccination with both Pfizer‐BioNTech and Moderna vaccines induced a robust humoral response in ART‐treated HIV patients with preserved CD4 cell count. A diminished humoral immune response to vaccination against COVID‐19 in PLWH with unrestored CD4 count implied the need of specific vaccination schemes.
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