Post-Mrna Vaccination SARS-CoV-2 IGG Concentrations and Surrogate Virus Neutralization Response Compared by HIV Status and Type of Vaccine: A Matched Case-Control Observational Study

Abstract

Background: Limited data is available on whether there are differences in the humoral response to mRNA SARS-CoV-2 vaccination by HIV status. We compared surrogate virus neutralization tests (sVNT) and anti-receptor-binding-domain (RBD) IgG concentrations by HIV status, as well as if responses differed by mRNA vaccine type. Methods: Remnant serum samples were collected during the month of May 2021 from all people living with HIV (PLWH) undergoing outpatient laboratory testing in a U.S. municipal health-care system. Samples from 100 PLWH were then matched on the same number of days following second mRNA vaccination, age (+/- 5 years), birth sex, and type of mRNA vaccine to samples from 100 adults receiving care for chronic conditions at the same hospital. Antibody responses were measured using a previously validated sVNT and anti-RBD IgG, with non-response defined as the limit of detection at <10 reciprocal titer and <10 relative fluorescent units respectively. Responses were compared by HIV status using mixed-effects models. Findings: In each matched group there were 13 women; 25 received the mRNA-1273 vaccine and 75 received the BNT162b2 vaccine. There were 2.43-fold higher odds of sVNT non-response among PLWH [95% confidence interval (CI)=1.09-5.39]. Although few individuals did not mount an anti-RBD IgG response (12 among PLWH vs. 5; p=0.08), continuous anti-RBD concentrations were 43% lower among PLWH (GMR 0.57; 95% CI=0.36-0.88). After adjusting for age, sex, and days post-second-vaccination, receipt of the BNT162b2 vs. mRNA-1273 vaccine was associated with 77% lower sVNT titers, each 100-cell increase in CD4+ T-cell count was associated with 22% higher titers (GMR 1.22; 95% CI=1.09-1.37), while unsuppressed RNA>200 copies/mL was associated with 89% lower titers (GMR 0.11; 95% CI=0.01-0.84). Interpretation: PLWH had lower than expected response to mRNA SARS-CoV-2 vaccines, particularly among those with low CD4+ T-cell counts, unsuppressed HIV RNA, and those who received the BNT162b2 vaccine. Funding: This research was supported by U.S. National Institute of Allergy and Infectious Diseases (NIAID) R01AI158013 (M.A.S. and M.G.), and U.S. NIAID P30AI027763 (M.G.) Declaration of Interest: DVG reports personal fees from Gilead Sciences outside the submitted work. All other authors declare no competing interests. Ethical Approval: As only remnant samples were used, the University of California, San Francisco IRB did not require informed consent for study participation. The UCSF IRB # is 20-30387.