Association Between Human Immunodeficiency Virus Viremia and Compromised Neutralization of Severe Acute Respiratory Syndrome Coronavirus 2 Beta Variant

Abstract

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may be associated with worse clinical outcomes in people with human immunodeficiency virus (HIV) (PWH). We report anti-SARS-CoV-2 antibody responses in patients hospitalized with coronavirus disease 2019 in Durban, South Africa, during the second SARS-CoV-2 infection wave dominated by the Beta (B.1.351) variant.

Methods: Thirty-four participants with confirmed SARS-CoV-2 infection were followed up with weekly blood sampling to examine antibody levels and neutralization potency against SARS-CoV-2 variants. Participants included 18 PWH, of whom 11 were HIV viremic.

Results: SARS-CoV-2-specific antibody concentrations were generally lower in viremic PWH than in virologically suppressed PWH and HIV-negative participants, and neutralization of the Beta variant was 4.9-fold lower in viremic PWH. Most HIV-negative participants and antiretroviral therapy-suppressed PWH also neutralized the Delta (B.1.617.2) variant, whereas the majority of viremic PWH did not. CD4 cell counts <500/μL were associated with lower frequencies of immunoglobulin G and A seroconversion. In addition, there was a high correlation between a surrogate virus neutralization test and live virus neutralization against ancestral SARS-CoV-2 virus in both PWH and HIV-negative individuals, but correlation decreased for the Beta variant neutralization in PWH.

Conclusions: HIV viremia was associated with reduced Beta variant neutralization. This highlights the importance of HIV suppression in maintaining an effective SARS-CoV-2 neutralization response.

Keywords: Beta variant; COVID-19; HIV; SARS-CoV-2; antibodies; antiretroviral therapy; neutralization.

Figure 1.

Effect of human immunodeficiency virus (HIV) status and suppression on severe acute respiratory syndrome coronavirus 2 anti-spike receptor-binding domain (RBD) antibodies. Anti-RBD antibody concentrations and surrogate virus neutralization test (sVNT) values in study participants with coronavirus disease 2019 (COVID-19), including HIV-negative individuals (first column) and virologically suppressed (second column) and viremic (third column) people with HIV. Individual participants’ data points are shown. Linear trends in pooled data are shown as transparent ribbons; 95% confidence intervals, as thick dotted lines. For immunoglobulin (Ig) G and IgA, baseline cutoffs, indicated by horizontal thin dotted lines, were defined as means plus 3 standard deviations of prepandemic control plasma concentrations (IgG, 1160 ng/mL; IgA, 283 ng/mL). For sVNT, the manufacturer’s recommended cutoff of 30% is shown. COVID-19 was diagnosed by means of reverse-transcription quantitative polymerase chain reaction. A–C, IgG and IgA concentrations and percentage of surrogate virus neutralization over time. D–F, Maximum IgG and IgA concentrations and sVNT titers per participant. Error bars show means and standard deviations. *P = .03 (Kruskal-Wallis test). Abbreviations: Neg, HIV negative; Sup, HIV suppressed; Vir, HIV viremic. G–I, Proportions of participants who seroconverted at any point for IgG, IgA, or sVNT, defined as having a sample above the cutoff, shown in color.

Figure 2.

Effect of human immunodeficiency virus (HIV) status and suppression on antibody neutralization capacity. A, Neutralization of wave-concordant Beta virus and cross-neutralization of ancestral D614G and Delta virus by plasma samples from HIV-negative individuals and HIV-suppressed people with HIV (PWH). Friedman’s test was used to compare matched participant data across the different variants. *P = .03; ***P < .001. Abbreviation: FRNT₅₀, 50% focus reduction neutralization titer. B, Neutralization of D614G, Beta, and Delta viruses by plasma samples from viremic PWH. C–E, Neutralization titers of plasma samples from HIV-negative participants (Neg) and HIV-suppressed PWH (Sup) compared with viremic PWH (Vir) for ancestral D614G, Beta, and Delta viruses. Error bars show geometric means and geometric standard deviations. Dotted lines in A­–E show the minimum tested dilution of 1:20 for the neutralization assay. *P = .0499; Mann-Whitney test was used to compare patient groups. F–H, Fractions of HIV-negative individuals and HIV-suppressed and viremic PWH who had detectable neutralization (above limit of quantification) of ancestral D614G, Beta, and Delta viruses. The fraction of viremic PWH able to neutralize was lower but with borderline significance (P = .0499; Fisher exact test).

Figure 3.

Comparison of surrogate virus neutralization test (sVNT) with live virus neutralization assays (VNAs). A, First infection wave samples from participants enrolled in 2020 tested against D614G virus. B, C, Samples from participants enrolled in the Beta infection wave in early 2021, tested against D614G (B) and Beta (C) viruses. Squares represent human immunodeficiency virus (HIV)–negative individuals; circles, people with HIV (PWH); solid curve, sigmoidal 4-parameter curve fitted to all samples; dashed curves, separate models for HIV-negative and PWH groups; dotted lines, positive/negative cutoff of 30% for sVNT as recommended by the manufacturer and minimum tested dilution of 1:20 for neutralization assay. Abbreviation: FRNT₅₀, 50% focus reduction neutralization titer.