To date, few studies have been published on the immune response to the BNT162b2 vaccine in people with HIV (PWH) [1–3]. In an ongoing prospective open-label clinical trial, we have evaluated antibody response to the BNT162b2 vaccine in 90 individuals with HIV infection on antiretroviral therapy (ART), and 90 HIV-negative controls.
PWH at least 18 years of age were enrolled at Karolinska University Hospital, Stockholm, Sweden, as part of a larger prospective BNT162b2 (Comirnaty; Pfizer/BioNTech, Germany/EU) vaccination trial, as previously described . Here, we present detailed subgroup analyses of PWH, stratified by CD4+ T-cell counts or HIV viral load at baseline. The two vaccine doses were administered 3 weeks apart, and blood samples were collected at baseline (day 0), day 21, and day 35.
The trial was registered at clinicaltrials.gov (no. 2021-000175-37). Ethical approval was obtained from the Swedish Ethical Review Authority (ID 2021-00451). SARS-CoV-2 spike IgG assay was performed in serum (Elecsys Anti-SARS-CoV-2 S; Roche Diagnostics International Ltd, Switzerland). Dilution of serum up to 1/100 was done when needed, allowing measurement of IgG levels up to 25 000 U/ml, in contrast to using standard upper limit level of 250 U/ml. CD4+ and CD8+ T-cell counts, and HIV viral load were determined by flow cytometry and Cobas Amplicor (Roche Molecular Systems Inc., USA), respectively. Statistical analyses were performed in JMP version 15 (SAS) and Prism version 9 (Graphpad).
We included 90 PWH and 90 controls in the study (supplemental Table 1, https://links.lww.com/QAD/C411). Eight PWH were excluded from the final analysis; one opted out from the study at an early stage and seven were seropositive for SARS-CoV-2 spike IgG at baseline. Four controls were excluded from analysis; two were seropositive at baseline and two tested positive for SARS-CoV-2 after the first dose of vaccine and did not receive a second dose. Day 35 data were missing from three PWH and four controls.
At baseline, all patients were on ART (on average 10.8 years) and 80% of patients were treated with integrase inhibitors. CD4+ T-cell count was 565 (280–723) cells/μl and 86% of PWH had HIV RNA less than 50 copies/ml. Forty (49%) patients had CD4+ T-cell nadir at less than 200 cells/μl. There were no significant differences in age, BMI or comorbidities between the PWH and control group.
There was no difference in the proportion of patients experiencing typical local and systemic vaccine reactions between PWH and the healthy controls . Severe adverse events (SAEs) were observed in two PWH, of whom one with vasovagal reaction was possibly linked to the vaccine.
At day 35 after vaccination, the seroconversion rate in PWH was 98.7% (78/79), and 100% (n = 82) in controls. However, PWH developed lower SARS-CoV-2 spike IgG levels than controls (P = 0.0012) (Fig. 1a), with 1613 (897–2643) U/ml for PWH vs. 2192 (1398–3651) U/ml for controls. Only one patient did not seroconvert, a 69-year-old individual with an autoimmune disease, without immunosuppressive treatment. One 34-year-old patient with no comorbidities seroconverted at day 35 with very low titers. Both had low CD4+ T-cell counts, of 90 (14%) and 40 (4%) cells/μl, respectively. PWH with viral load more than 50 copies/ml at baseline developed lower IgG levels than patients with viral load less than 50 copies/ml (Supplemental Fig. 1, https://links.lww.com/QAD/C412). In contrast, spike IgG levels were not significantly different between groups when the cohort was stratified based on the baseline CD4+ cell counts (Fig. 1b), nadir CD4+ T-cell counts, duration of ART, comorbidities, BMI, or CD4+/CD8+ ratio.
At baseline, 10 (13%) patients had detectable HIV RNA (range 56–18 000 copies/ml). At day 21, only six (7.8%) and at day 35 only three (4%) had viral load above 50 copies/ml (range 53–175 and 57–17100 copies/ml, respectively). The HIV viremia in two of the individuals with detectable HIV RNA at day 35 could be explained with poor ART adherence, thus leaving only one patient with potential vaccine-related HIV RNA blip.
We found a high rate of seroconversion in PWH following two doses of the BNT162b2 vaccine, regardless of CD4+ T-cell count. We observed good safety and lack of vaccine-induced HIV RNA blips. Still, we found that PWH developed significantly lower levels of SARS-CoV-2 spike IgG than controls 2 weeks after the second dose. In addition, we present that patients with baseline viral load more than 50 copies/ml had lower levels of spike IgG.
Although PWH undergoing ART generally have restored CD4+ T-cell numbers, they may not have full immune reconstitution despite long-term effective ART. One of the poor vaccine responders who seroconverted with very low spike IgG titers was recently diagnosed with HIV with 3 months of ART. Vaccine-induced immune activation may in theory promote HIV viral transcription from latency, thus affecting the viral reservoir . Nevertheless, we did not find blips following the vaccination in our cohort.
To our knowledge, this is the first study linking lower anti spike antibody levels to individuals with HIV viremia, which may mirror poorer adherence or shorter time on ART. Our results regarding seroconversion and levels of serum spike IgG corroborate with the findings of Levy et al.. A recent study modeling the decay of the neutralization titer over the first 250 days after immunization predicted a significant loss in protection from SARS-CoV-2 infection . As PWH had lower spike IgG levels compared with controls, it is important to follow this cohort to assess the need for eventual booster doses.
The limitation of our study may be skewed inclusion of individuals with an increased risk for severe COVID-19. Therefore, the study cohort does not reflect our general patient population in terms of age and comorbidities.
In conclusion, the SARS-COV-2 mRNA vaccine generally elicited a robust antibody response in PWH and should be encouraged in all PWH regardless of immune status. The finding of lower IgG levels in PWH warrant further study of the IgG levels over time in PWH, especially in individuals with HIV viremia before vaccination, to assess the kinetics of humoral response.
The COVAXID study group author contributors: Peter Bergman (Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden and Department of Laboratory Medicine, Clinical Microbiology, Karolinska Institutet, Stockholm, Sweden), Ola Blennow (Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden, Department of Transplantation, Karolinska University Hospital, Stockholm, Sweden and Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden), Lotta Hansson (Department of Hematology, Karolinska University Hospital, Stockholm, Sweden and Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden), Stephan Mielke [Department of Laboratory Medicine, Biomolecular and Cellular Medicine, Karolinska Institutet, Stockholm, Sweden and Department of Cellular Therapy and Allogeneic Stem Cell Transplantation (CAST), Karolinska University Hospital Huddinge, Stockholm, Sweden], Puran Chen (Department of Medicine Huddinge, Center for Infectious Medicine, Karolinska Institutet, Stockholm, Sweden), Marcus Buggert (Department of Medicine Huddinge, Center for Infectious Medicine, Karolinska Institutet, Stockholm, Sweden), Hans-Gustaf Ljunggren (Department of Medicine Huddinge, Center for Infectious Medicine, Karolinska Institutet, Stockholm, Sweden), Per Ljungman [Department of Cellular Therapy and Allogeneic Stem Cell Transplantation (CAST), Karolinska University Hospital Huddinge, Stockholm, Sweden and Department of Medicine Huddinge, Hematology, Karolinska Institutet, Stockholm].
Conflicts of interest
There are no conflicts of interest.
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