Hepatitis B vaccine antibody response and the risk of clinical AIDS or death.

Michael L Landrum,Brian K Agan,Anuradha Ganesan,Katherine Huppler Hullsiek,Jason F Okulicz,Tahaniyat Lalani,Nancy F Crum-Cianflone,Amy C Weintrob,Robert J O'Connell,Helen M Chun,Elvin Hsing Geng

doi:10.1371/journal.pone.0033488

Michael L Landrum, Brian K Agan + Show 9 more

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https://doi.org/10.1371/journal.pone.0033488

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Abstract

BackgroundWhether seroresponse to a vaccine such as hepatitis B virus (HBV) vaccine can provide a measure of the functional immune status of HIV-infected persons is unknown.This study evaluated the relationship between HBV vaccine seroresponses and progression to clinical AIDS or death.Methods and FindingsFrom a large HIV cohort, we evaluated those who received HBV vaccine only after HIV diagnosis and had anti-HBs determination 1–12 months after the last vaccine dose. Non-response and positive response were defined as anti-HBs <10 and ≥10 IU/L, respectively. Participants were followed from date of last vaccination to clinical AIDS, death, or last visit. Univariate and multivariable risk of progression to clinical AIDS or death were evaluated with Cox regression models. A total of 795 participants vaccinated from 1986–2010 were included, of which 41% were responders. During 3,872 person-years of observation, 122 AIDS or death events occurred (53% after 1995). Twenty-two percent of non-responders experienced clinical AIDS or death compared with 5% of responders (p<0.001). Non-response to HBV vaccine was associated with a greater than 2-fold increased risk of clinical AIDS or death (HR 2.47; 95% CI, 1.38–4.43) compared with a positive response, after adjusting for CD4 count, HIV viral load, HAART use, and delayed type hypersensitivity skin test responses (an in vivo marker of cell-mediated immunity). This association remained evident among those with CD4 count ≥500 cells/mm3 (HR 3.40; 95% CI, 1.39–8.32).ConclusionsHBV vaccine responses may have utility in assessing functional immune status and risk stratificating HIV-infected individuals, including those with CD4 count ≥500 cells/mm3.

Highlights

Infection with HIV-1 is unsparing, resulting in perturbations in nearly every immune cell type and immune response
In the SILCAAT and ESPRIT clinical trials, which evaluated the use of interleukin-2 (IL-2) in subjects receiving highly active antiretroviral therapy (HAART), having a higher CD4 cell count as the result of IL-2 treatment did not correspond to a lower risk of experiencing opportunistic disease or death from any cause, suggesting that a greater number of CD4 lymphocytes did not necessarily equate with reconstitution of immune function [4]
Univariate and multivariate risk of clinical acquired immune definiciency syndrome (AIDS) or death In univariate analysis, those with non-response to hepatitis B virus (HBV) vaccine had a 4-fold increased risk of AIDS or death following the last dose of vaccine compared with those who did respond (HR 4.01; 95% confidence intervals (CI) 2.37–6.80) (Table 4)

Summary

Introduction

Infection with HIV-1 is unsparing, resulting in perturbations in nearly every immune cell type and immune response. CD4 cell count and plasma HIV viral load (VL) are commonly used to assess HIV disease stage [1,2,3], they may not provide a complete measure of the functional immunological status of an HIV-infected person, despite receipt of therapy. Other parameters reflective of immune function, such as responses to vaccines, may serve as important immunological tools to identify subsets of HIV-infected subjects who manifest functional impairment in the immune system, despite high CD4 cell counts or low VL before or after receipt of HAART. Whether seroresponse to a vaccine such as hepatitis B virus (HBV) vaccine can provide a measure of the functional immune status of HIV-infected persons is unknown.This study evaluated the relationship between HBV vaccine seroresponses and progression to clinical AIDS or death

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