Safety and Immunogenicity of Inactivated COVID-19 Vaccines Among People Living with HIV in China

Abstract

Purpose Vaccination reduces the incidence of severe COVID-19 and death and effectively limits viral spread. Concerns have been raised about COVID-19 vaccine responses in the large population of HIV-infected patients. This study aims to explore the safety and immunogenicity of the inactivated COVID-19 vaccine in people living with HIV (PLWH). Patients and Methods All participants in this study already had their second dose of an inactivated COVID-19 vaccine at least 14 days earlier, without a history of SARS-CoV-2 infection. The primary safety outcomes were the incidence of adverse reactions and changes in CD4 + T-cell counts. SARS-CoV-2 IgG and neutralizing antibody responses to the D614G variant and delta variant were measured for immune response assessment. Results Forty-seven HIV-infected patients and 18 healthy donors (HDs) were enrolled in this study. Adverse reactions were mild or self-limiting and were reported in 19.1% of HIV-infected patients. Most PLWH developed antibody responses against the inactivated COVID-19 vaccine. The longitudinal analysis of antibody responses in PLWH (median interval between detection and complete vaccination, 59 days) showed that antibodies were maintained for at least three months, though their titers were reduced. However, the antibody-positive rates in PLWH were significantly lower than those in HDs. Additionally, compared to HDs (Geomean titers (GMT) of 165 for D614G and GMT of 72 for delta), the neutralizing antibody titers against the two variants in PLWH (GMT of 43 for D614G and GMT 13 for delta) were decreased significantly (p = 0.018 and p < 0.001, respectively). HIV-infected patients with CD4 + T-cell counts ≤350 cells/μL appeared to exhibit a poor antibody response to inactivated vaccination. Conclusion Inactivated COVID-19 vaccines appear to be efficacious in PLWH. However, antibody responses in HIV-infected patients are inferior to those in healthy individuals, especially PLWH with lower CD4 + T-cell counts.

The safety and immunogenicity of a two-dose schedule of CoronaVac, and the immune persistence of vaccination for six months, in people living with HIV: A multicenter prospective cohort study

“…This phenomenon may be associated with the dysfunction of the immune system among PLWH. All reported AEs were mild or self-limited, which was consistent with other studies that investigated inactivated vaccines among PLWH ( 18 , 20 , 24 ).…”

“…This study has several strengths. First of all, the participants were prospectively followed up for 6 months, which was longer than other previous studies in China ( 18 , 19 , 22 ). The follow-up period is important and could provide compelling evidence to identify an optimal vaccination schedule for PLWH.…”

“…However, few studies published data on the safety and immunogenicity of inactivated vaccines in PLWH. In a study that investigated 47 PLWH in Beijing, the antibody levels in PLWH have been maintained for at least three months, but PLWH with lower CD4+T-cell counts showed a poor antibody response to the inactivated vaccines ( 18 ). In studies conducted in Kunming ( 19 ), Chongqing ( 20 ), and Wuhan ( 21 ), PLWH displayed weaker immune responses to COVID-19 vaccination compared to HIV-negative participants.…”

Immunologic Interplay Between HIV/AIDS and COVID-19: Adding Fuel to the Flames?

“…Humoral responses to NVX-CoV2373 have been shown lower in PLWH as compared to people without HIV, especially in those without prior SARS-CoV-2 infection [ 108 •]. Immunogenicity of inactivated vaccines in PLWH have been reported similar [ 109 , 110 •] or lower [ 111 – 113 ] than in general population according to different studies, but invariably reduced in those with low CD4 + T-cell counts and/or CD4/CD8 ratio [ 109 , 110 •, 111 ].…”

“…[ 109 ] CoronaVac (2 doses) Cross-sectional, observational study (China) 55 PLWH: all males; mean age: 36 years (SD: 11) 21 HIV-negative controls: 17 (81%) males, 4 (19%) females; mean age: 35 years (SD: 8) CD4 + T-cell count strata: - ≥ 350/µL: immunological responders - < 350/µL: immunological non-responders All PLWH on cART for at least 1 year HIV-RNA < 50 copies/mL in all participants Participants with prior SARS-CoV-2 infection excluded Anti-RBD IgG (ELISA) Time-points: 2–18 weeks after the second dose Similar anti-RBD IgG in PLWH and HIV-controls Lower humoral response in PLWH with CD4 + T-cell counts < 350/µL Han, et al . [ 111 ] CoronaVac or BBIBP-CorV (2 doses) Non-interventional study (China) 47 PLWH: 45 (95.7%) males, 4 (4.3%) females; median age: 34 years (IQR: 26–42) 18 HIV-negative controls: all males; median age: 40 years (IQR: 28–57) Median CD4 + T-cell count: 474 cells/µL (IQR: 145–926) CD4 + T-cell count strata: - ≤ 350 cells/µL: suboptimal immune recovery - > 350 cells/µL: good immune recovery All PLWH on cART for at least 6 months Median plasm HIV-RNA: 20 copies/mL (IQR: 20–163.8) Participants with prior SARS-CoV-2 infection excluded Anti-S IgG (magnetic particles chemiluminescence immunoassay) Neutralizing antibody activity (pseudovirus neutralization assay) Time–points: 28 days after vaccination Lower levels of IgG and neutralization activity (against both D614G and Delta variant) in PLWH compared to HIV-negative controls Even lower humoral responses in PLWH with low CD4 + T-cell counts Feng, et al . [ 110 •] BBIBP-CorV (2 doses) Open-label two-arm non-randomized study (China) 42 PLWH: 29 males, 13 females; mean age: 42.7 years 28 HIV-negative controls: 16 males, 12 females; mean age: 37.8 years Mean CD4 + T-cell count: 659/µL (SD: 222) All PLWH on cART Plasma HIV-RNA: - > 20 copies/mL: n = 12 - < 20 copies/mL: n = 8 - undetectable: n = 22 Participants with prior SARS-CoV-2 infection excluded Anti-RBD Ig (ELISA) Neutralizing antibody activity (chemiluminescent reaction; spike-ACE2 binding inhibition assay) SARS-CoV-2–specific T-cells (ICS by flow cytometry after stimulation of PBMCs with spike peptide pool) Time-points: baseline; 4 weeks after first dose; 4 weeks after second dose …”