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  HIV Glasgow 2022
23-26 October
Virtual Meeting
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Older people with well-controlled HIV have similar antibody and higher T-cell responses after vaccination against SARS-CoV-2 compared to demographically and lifestyle-comparable people without HIV
  Higher Immune Response to COVID Vax in Older HIV+ Than Matched HIV-
HIV Drug Therapy Glasgow, October 23-26, 2022
Mark Mascolini
Older people with HIV in an Amsterdam cohort had a stronger cellular immune response to SARS-CoV-2 than similar HIV-negative people both before and after SARS-CoV-2 vaccination [1]. Antibody responses to the coronavirus were similar with and without HIV in this 55-and-older group. The AGEhIV Cohort Study Group cautioned that these results may not apply to all older people with HIV because their group was mostly Caucasian and had well-controlled HIV infection and high CD4 counts.
AGEhIV researchers who conducted this study noted that available evidence on humoral (antibody-driven) immune responses to SARS-CoV-2 vaccination is mixed because most studies compare HIV-positive people with healthy HIV-negatives often differing in age or sex. And scanty data address cellular immune responses to these vaccines in people with HIV. Determining COVID vaccine immune responses in older people with HIV is especially important because responses may differ between older and younger people, and older people run a higher risk of severe COVID disease.
This analysis compared 195 HIV-positive people with 246 HIV-negative people, everyone in both groups 55 or older. AGEhIV researchers draw HIV-negative controls from sexually transmitted infection clinics, so they have lifestyles similar to people with HIV. For this analysis, study participants made 5 scheduled visits to give blood samples and complete questionnaires. They gave an additional blood sample 4 to 13 weeks after the last dose of their primary SARS-CoV-2 vaccination course, which could use the Pfizer, Moderna, AstraZeneca, or Johnson & Johnson vaccine.
In samples drawn before and after vaccination, researchers measured antibody response as SARS-CoV-2 nucleocapsid IgA, IgM, and IgG antibody response; spike IgG antibody response; and SARS-CoV-2 neutralization titers against ancestral, Delta, and Omicron BA1 viral variants. They assessed cellular immune response as interferon-gamma (IFNg) release after SARS-CoV-2 peptide stimulation.
In all study participants the AGEhIV team compared humoral and cellular immune responses between people with and without HIV grouped by prior SARS-CoV-2 infection. They also compared a subgroup of 40 people with HIV and 40 controls with no prior SARS-CoV-2 infection who got two doses of the Pfizer, Moderna, or AstraZeneca vaccine. Everyone with HIV in this subgroup had an HIV load below 50 copies. The researchers stratified them into four groups of 10 people each based on lowest-ever CD4 count then matched this HIV subgroup to 40 people without HIV by age, sex, and vaccine type.
The 195 people with HIV had a median age of 63.3 years, similar to the control group's 61.6 years (P = 0.145). Large majorities in the HIV and control groups were Caucasian (97.4% and 96.4%). The HIV group had a higher proportion of men (94.4% vs 85.8%, P = 0.003) and higher proportions with 1 or 2 comorbidities (49.2% vs 31.7%) and 3 or more comorbidities (10.3% vs 5.7%) (P < 0.001).
Median current CD4 count was high in the HIV group but still significantly lower than in HIV-negative controls (640 vs 810, P < 0.001). Median current CD4/CD8-cell ratio was also significantly lower in the HIV group (0.86 vs 1.87, P < 0.001). A median 22.6 years had elapsed since HIV diagnosis, and median lowest-ever CD4 count was 180. All but 2 of these 195 people with HIV had an undetectable viral load.
About two thirds in the HIV-positive and negative groups got the Pfizer vaccine, while most of the rest got the AstraZeneca shot. Median days between the last vaccine dose and the postvaccination sample were similar in the HIV and control groups-64 and 70 days (P = 0.262). In both groups 10% had SARS-CoV-2 infection before the prevaccination sample and 4% in each group between the pre- and postvaccination samples.
Pre- and postvaccination anti-S IgG levels proved similar in people with and without HIV regardless of whether they had prior SARS-CoV-2 infection. Post-vaccination anti-S IgG titers were higher in people who got an mRNA vaccine (Pfizer or Moderna) than in those who got the AstraZeneca or Johnson & Johnson vaccines.
Multivariable linear regression analysis linked current CD4/CD8 ratio below 1.0 to a weaker anti-S IgG response in both the HIV group and HIV-negative controls. This analysis also tied more days between the last vaccine dose and sampling for this study to lower anti-S IgG. Factors favoring a higher anti-S IgG response in this analysis were using an mRNA vaccine versus a vector-based vaccine, having prior SARS-CoV-2 infection, and female gender. There was a trend toward a better antibody response in people with versus without HIV infection (coefficient +0.07, 95% confidence interval [CI] -0.03 to +0.17, P = 0.190).
Neutralization of ancestral, Delta, and Omicron BA1 variants differed hardly at all between people with and without HIV. For the ancestral viral variant, multivariable linear regression determined that being younger than 60 versus 70 or older and getting the Moderna versus the Pfizer vaccine favored higher neutralization levels. This analysis linked two factors to lower neutralizing antibody levels-more days between the last vaccine dose and sampling, and current CD4/CD8 ratio below 1.0. For Delta variant SARS-CoV-2, getting the Moderna shot rather than the Pfizer product favored higher neutralization levels.
Cellular immune responses to SARS-CoV-2 before and after vaccination were higher in HIV-positive participants without prior SARS-CoV-2 than in HIV-negative controls without prior infection. Pre- and postvaccination cellular immune responses were similar in people with and without HIV who had prior COVID. Postvaccination cellular responses did not differ substantially between mRNA and vector-based vaccines.
Multivariable analysis confirmed an association between HIV infection (versus no HIV) and a better IFNg release postvaccination cellular immune response (coefficient +0.63, 95% CI +0.34 to +0.93, P < 0.001). SARS-CoV-2 infection before vaccination also conferred a better cellular immune response (coefficient +30.49, 95% CI +14.04 to +46.88, P < 0.001). More days between the last vaccination dose and sampling was associated with a lower cellular response (coefficient -0.10, 95% CI -0.18 to -0.01, P = 0.021). And current CD4/CD8 ratio below 1.0 was associated with a diminished cellular response in people with HIV.
The AGEhIV investigators concluded that antibody-driven immune responses after vaccination are similar in older people "with well-controlled HIV and highly comparable controls." Compared with HIV-negative controls, the HIV group had higher cellular immune responses before and after SARS-CoV-2 infection.
1. Verburgh ML, van Pul L, Grobben M, et al. Older people with well-controlled HIV have similar antibody and higher T-cell responses after vaccination against SARS-CoV-2 compared to demographically and lifestyle-comparable peo