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Immunogenicity of mRNA vaccination against SARS-CoV-2 in persons living with HIV (PLWHs) with low CD4 count or previous AIDS
Immune Response to mRNA COVID Vaccines Weaker in HIV+ With Low CD4s
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18th European AIDS Conference, EACS 2021, October 27-30, 2021, London
Mark Mascolini
HIV-positive people with a sub-200 CD4 count had a worse immune response to the Pfizer and Moderna mRNA COVID vaccines than did HIV-positive people with higher CD4 counts or healthy HIV-negative people in a 335-person analysis in Italy [1]. But overall the vaccines produced robust humoral and cell-mediated immune responses in these antiretroviral-treated people with HIV.
Italian researchers in the HIV-VAC Study Group noted that observational studies suggest a worse prognosis with COVID-19 in HIV-positive people than in the general population. Some work, they added, suggests that a higher risk of severe COVID-19 with HIV can be traced to lower IgG concentrations and low neutralizing antibody levels. And data on immune responses to COVID vaccines in HIV-positive people, especially people with low CD4 counts, remain scant.
To address these issues, the HIV-VAC Study team focused on HIV-positive people who had an mRNA COVID vaccine (Pfizer or Moderna). They stratified these individuals into three CD4 brackets: below 200, 200 to 500, and above 500. Everyone with HIV was taking antiretroviral therapy. The researchers estimated immune responses at the time of the first dose (T0), the time of the second dose (T1), and 1 month after the second dose (T2) by three measures: (1) binding antibody units (BAU/mL) of SARS-CoV-2 receptor binding domain (RBD) IgG, (2) SARS-CoV-2 neutralizing titers (levels) assessed by microneutralization assay, and (3) T-cell-mediated immune responses in whole blood (interferon-gamma production after S peptide stimulation). They compared results across the three CD4-count brackets and between people with HIV and HIV-negative healthcare workers who got the Pfizer vaccine.
The analysis involved 166 people with HIV infection-32 in the sub-200 CD4 group, 56 in the 200-500 group, and 78 in the over-500 group. Proportions of women in those three groups were 25%, 16%, and 13%, and median ages were 57, 54, and 54. Median HIV infection duration was significantly longer in the sub-200 group than in the 200-500 and over-500 groups (22.2 vs 9.2 vs 11.0 years, P = 0.033). The sub-200 group had a lower proportion with an AIDS diagnosis (37.5% vs 46.4% vs 47.4%, P < 0.001) as well as a lower proportion with an HIV load below 50 copies (68.8% vs 92.9% vs 100%, P < 0.001) and a lower nadir CD4 count (49 vs 63 vs 174, P < 0.001). Current median CD4 counts across the three groups were 140, 335, and 727 (P < 0.001). Higher proportions in the sub-200 and 200-500 groups than in the over-500 group got the Pfizer vaccine (68.8% and 67.9% vs 44.9%, P = 0.010).
In all three CD4 strata, the RBD-binding IgG response improved significantly from T0 to T1 and from T0 to T2 (P < 0.001 for all differences). Cell-mediated immunogenicity rose significantly from T0 and T1 to T2 in the sub-200 CD4 group (P < 0.001) and from T0 to T1 and T0 to T2 in the other two CD4 groups (P < 0.001).
Vaccine responses were significantly lower in the sub-200 CD4 group than in either the over-500 group or healthy controls for (1) detectable RBD-binding IgG (P = 0.021 and P < 0.001), (2) median binding antibody units of RBD-binding IgG (P < 0.001 for both comparisons), (3) neutralizing antibody >/= 10 (P = 0.002 and P < 0.001), and (4) median reciprocal dilution values by microneutralization assay (P < 0.001 for both comparisons). The latter three values were significantly lower in the 200-500 CD4 group than in healthy controls (P < 0.001, P = 0.019, P = 0.05). And median reciprocal dilution values by microneutralization assay were significantly lower in the 200-500 CD4 group than in the over-500 group (P < 0.001).
At T2 humoral immunogenicity by anti-RBD (BAU/mL) was significantly lower in the sub-200 CD4 group than in the 200-500 group (P < 0.05), the over-500 group (P < 0.001), or healthy controls (P < 0.001). Humoral immunogenicity measured that way was also significantly lower in the 200-500 CD4 group than in healthy controls (P < 0.001) and in the over-500 group than in healthy controls (P < 0.05). Cell-mediated immunogenicity measured by interferon-gamma was significantly lower at T2 in (1) the sub-200 group than the 200-500 group (P < 0.01), the over-500 group (P < 0.001), and healthy controls (P < 0.001), and (2) the 200-500 group than healthy controls (P< 0.05).
Multivariable linear regression to explore associations between current CD4 count and humoral immune response to mRNA vaccination adjusted for age, years of HIV infection, current CD4 count, nadir CD4 count, HIV load below 50 copies, type of mRNA vaccine, and previous or current malignancy. This analysis determined that a current CD4 count below 200 (versus above 500) independently lowered RBD-binding IgG (BAU/mL): beta -0.64 (95% confidence interval [CI] -0.94 to -0.34, P < 0.001). Current CD4 count below 200 (versus above 500) also independently predicted lower neutralizing antibody titer: beta -0.41 (95% CI -0.70 to -0.12, P = 0.006). A CD4 count of 200-500 (versus over 500) did not predict these two humoral immune responses.
Current CD4 count below 200 (versus over 500) also independently predicted cell-mediated immune response to vaccination by interferon-gamma release after S peptide stimulation: beta -0.74 (95% CI -1.13 to -0.34, P < 0.001). Again, CD4 count between 200 and 500 did not independently predict this response.
Despite consistently worse immune responses to mRNA COVID vaccines in HIV-positive people with a CD4 count below 200, the researchers concluded that "SARS-CoV-2 vaccination with an mRNA vaccine induced a robust humor and cell-mediated immune response in most [emphasis added] people living with HIV on antiretroviral therapy." They stressed that the HIV-negative healthy control group was not matched to the HIV-positive groups, although comparisons controlled for age and sex. They also cautioned that the short follow-up after two vaccination injections allows no insights into waning immune response over time in people with HIV.
Reference
1. Antinori A, Cicalini S, Meschi S, et al. Immunogenicity of mRNA vaccination against SARS-CoV-2 in persons living with HIV (PLWHs) with low CD4 count or previous AIDS. 18th European AIDS Conference, EACS 2021, October 27-30, 2021, London. Abstract OS4/3.
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