Immunogenicity of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection and Ad26.CoV2.S Vaccination in People Living With Human Immunodeficiency Virus (HIV)

Abstract

Background: People living with HIV (PLWH) have been reported to have a higher risk of more severe COVID-19 disease and death. We assessed the ability of the Ad26.CoV2.S vaccine to elicit neutralizing activity against the Delta variant in PLWH relative to HIV-negative individuals. We also examined effects of HIV status and suppression on Delta neutralization response in SARS-CoV-2-infected unvaccinated participants.

Methods: We enrolled participants who were vaccinated through the SISONKE South African clinical trial of the Ad26.CoV2.S vaccine in healthcare workers (HCWs). PLWH in this group had well-controlled HIV infection. We also enrolled unvaccinated participants previously infected with SARS-CoV-2. Neutralization capacity was assessed by a live virus neutralization assay of the Delta variant.

Results: Most Ad26.CoV2.S vaccinated HCWs were previously infected with SARS-CoV-2. In this group, Delta variant neutralization was 9-fold higher compared with the infected-only group and 26-fold higher relative to the vaccinated-only group. No decrease in Delta variant neutralization was observed in PLWH relative to HIV-negative participants. In contrast, SARS-CoV-2-infected, unvaccinated PLWH showed 7-fold lower neutralization and a higher frequency of nonresponders, with the highest frequency of nonresponders in people with HIV viremia. Vaccinated-only participants showed low neutralization capacity.

Conclusions: The neutralization response of the Delta variant following Ad26.CoV2.S vaccination in PLWH with well-controlled HIV was not inferior to HIV-negative participants, irrespective of past SARS-CoV-2 infection. In SARS-CoV-2-infected and nonvaccinated participants, HIV infection reduced the neutralization response to SARS-CoV-2, with the strongest reduction in HIV viremic individuals.

Keywords: Ad26.CoV2.S vaccines; HIV viremia; SARS-CoV-2; immunogenicity; neutralization.

Figure 1.

Effect of previous SARS-CoV-2 exposure on neutralization capacity elicited by Ad26.CoV2.S. Violin plots of neutralization capacity of Delta variant as FRNT₅₀ in SARS-CoV-2-infected unvaccinated, infected and vaccinated, vaccinated only, and pre-pandemic participants. PLWH are represented by orange points and HIV-negative participants by green points. Horizontal lines represent GMT. Participant numbers per category were n=62 (34 PLWH, 28 HIV) for infected unvaccinated, n=67 (18 PLWH, 49 HIV—) for infected vaccinated, and n=32 (8 PLWH, 24 HIV—) for vaccinated only. P values are as follows: ** <.01, **** <.0001 as determined by the Kruskal-Wallis test with Dunn multiple hypothesis correction. The dashed horizontal line denotes most concentrated plasma tested. Abbreviations: FRNT₅₀, focus reduction neutralization test (50 is the plasma dilution giving 50% neutralization); GMT, geometric mean titer; HIV, human immunodeficiency virus; Infect., infected; PLWH, people living with HIV; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; unvacc., unvaccinated; Vacc., vaccinated.

Figure 2.

Effect of HIV status on neutralization capacity elicited by Ad26.CoV2.S. (A-C) Neutralization capacity as FRNT₅₀ for Delta variant neutralization in SARS-CoV-2-infected unvaccinated (A), infected and vaccinated (B), and vaccinated only (C) participants. Solid horizontal lines represent GMT and dashed horizontal lines represent most concentrated plasma used. (D-F) frequency of participants with no detectable Delta variant neutralization (nonresponders) in SARS-CoV-2-infected unvaccinated (D), infected and vaccinated (f), and vaccinated-only (F participants. P values are as follows: * <.05, ** <.01, *** <.001, as determined for panels A-C by the Mann-Whitney U test and for panels D-F by Fisher's exact test. Abbreviations: Freq., frequency; FRNT₅₀, focus reduction neutralization test (50 is the plasma dilution giving 50% neutralization); GMT, geometric mean titer; HIV, human immunodeficiency virus; PLWH, people living with HIV; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; unvacc., unvaccinated.

Figure 3.

Effect of HIV viremia on neutralization capacity in infected unvaccinated participants. (A) Neutralization capacity as FRNT₅₀ for Delta variant neutralization in SARS-CoV-2—infected unvaccinated HIV viremic (n=10) versus infected unvaccinated HIV-suppressed (n=24) participants. The dashed horizontal line represents most concentrated plasma used. (B) Frequency of nonresponders in panel A. P values are as follows: P = .13 for (A) by the Mann-Whitney Utest and P = .0088 for (B) by Fisher's exact test. Abbreviations: Freq., frequency; FRNT₅₀, focus reduction neutralization test (50 is the plasma dilution giving 50% neutralization); HIV, human immunodeficiency virus; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; Supp., suppressed; Vir., viremic.

Figure 4.

Correlation between CD4 count and neutralization capacity. Pearson correlation of PRNT50 versus CD4 count in infected unvaccinated (A), infected and vaccinated (B), and vaccinated-only (C) participants. Solid lines represent linear regression and upper and lower lines represent 95% confidence intervals. r is the Pearson correlation coefficient. Green points are HIV-negative participants, purple points are PLWH with suppressed HIV viremia, and blue points are HIV viremic PLWH. Abbreviations: FRNT₅₀, focus reduction neutralization test; HIV, human immunodeficiency virus; PLWH, people living with HIV; supp., suppressed; vir., viremic.