Association between quantitative varicella-zoster virus antibody levels and zoster reactivation in HIV-infected persons

Background: Varicella-zoster virus (VZV) reactivation is common but difficult to predict in HIV-infected persons. Objective: Since qualitative VZV antibodies can determine past VZV disease or vaccination, we evaluated whether quantitative VZV antibody levels over time can predict future zoster. Study design: US Military HIV Natural History (NHS) participants with a zoster diagnosis at least 5years after HIV diagnosis (n=100) were included. Zoster-negative controls (n=200) were matched by age, race, gender, and CD4 count at HIV diagnosis. Repository plasma specimens collected at baseline and prior to zoster diagnosis were evaluated using a quantitative anti-VZV ELISA assay. Differences in quantitative VZV levels were analyzed by Wilcoxon Mann-Whitney and Fisher's exact tests. Results: Median CD4 count at HIV diagnosis was similar for cases and controls (535 [IQR 384-666] vs. 523 [IQR 377-690] cells/μL; p=0.940), but lower for cases at zoster diagnosis (436 [IQR 277-631] vs. 527 [IQR 367-744] cells/μL; p=0.007). Antiretroviral therapy (ART) use prior to zoster diagnosis was lower for cases (52.0%) compared to controls (64.5%; p=0.025). Cases had similar mean VZV antibody levels prior to zoster diagnosis compared to controls [2.25±0.85 vs. 2.44±0.96 index value/optical density (OD) ratio; p=0.151] with no difference in the change in antibody levels over time (0.08±0.71 vs. 0.01±0.94 index value/OD per year; p=0.276). Conclusion: Quantitative VZV antibody levels are stable in HIV-infected persons and do not predict zoster reactivation. Low CD4 count and lack of ART use appear to be better predictors of future zoster diagnosis.