Early Seroreversion After 2 Doses of Hepatitis A Vaccination in Human Immunodeficiency Virus–Positive Patients: Incidence and Associated Factors

Abstract

Serological responses (Seroresponse) and durability of hepatitis A virus (HAV) vaccination are reduced among human immunodeficiency virus (HIV)‐positive patients. Incidence of and associated factors with early seroreversion (loss of seroresponse) among HIV‐positive patients who have achieved seroresponses after two doses of HAV vaccination remain unclear. In this multicenter study, we followed HIV‐positive adults who had mounted seroresponses after completing two doses of HAV vaccination during a recent outbreak of acute hepatitis A between 2015 and 2017, a 1:4 case‐control study was conducted to identify factors associated with seroreversion. Case patients were those with seroreversion, and controls were those with similar follow‐up durations who were able to maintain seroresponses. During the study period, 49 of the 1,256 patients (3.9%) seroreverted after a median follow‐up of 611 days. In a case‐control study, seroreversion was more likely to occur in patients with a higher weight (adjusted odds ratio [aOR], 1.703; 95% confidence interval [CI], 1.292‐2.323, per 10‐kg increment) and HIV viremia at the time of vaccination (aOR, 2.922; 95% CI, 1.067‐7.924), whereas positive seroresponse at 6 months of HAV vaccination and higher CD4 lymphocyte counts at vaccination were inversely associated with early seroreversion with an aOR of 0.059 (95% CI, 0.020‐0.154) and 0.837 (95% CI, 0.704‐0.979, per 100‐cell/mm3 increment), respectively, in multivariable analyses. Conclusion: During an outbreak setting, early seroreversion following two‐dose HAV vaccination occurred in 3.9% of HIV‐positive patients. Lower and delayed seroresponses to HAV vaccination, a higher weight, and HIV viremia and lower CD4 lymphocyte counts at the time of HAV vaccination were associated with early seroreversion. Regular monitoring of seroresponse and booster vaccination might be warranted, especially in HIV‐positive adults with predictors of early seroreversion.

Reply

“…We thank Almasi‐Hashiana et al for their interest in and constructive comments on our study investigating the factors associated with seroreversion of anti–hepatitis A antibodies among human immunodeficiency virus (HIV)‐positive patients who had completed two doses of hepatitis A vaccination with documented serconversion . In an infectious disease outbreak, the risk of exposure to the infectious agent may evolve with time and location .…”

“…In the study, (1) we used individual 1:4 matching. After taking into account the matched variables in a conditional logistic regression model, we identify similar factors that were associated with early seroreversion after hepatitis A virus (HAV) vaccination, though with a weaker association (Table ).…”

Letter to the Editor: Methodological Issues Regarding the Matching in Matched Case‐Control Study

“…There are some concerns regarding matching in the Huang et al study. Firstly, in their study, the authors have not clearly specified which protocol they used to match cases and control (it seems that individual matching was done).…”

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We read with interest a recently published study by Huang et al (1) They conducted a case-control study including 49 seroreverters cases (as case group) and 196 nonseroreverters cases (as control) to identify associated factors of seroreversion and followed human immunodeficiency virus-positive adults who had mounted seroresponses after completing two doses of hepatitis A virus (HAV) vaccination during a recent outbreak of acute hepatitis A. The control group was matched with cases in terms of the month of first dose of HAV vaccination (±3 months), duration of follow-up (±3 months), and their hospitals.In observational studies, matching helps the researcher to control the confounding variables and ensures that groups are identical (or nearly so) with respect to the distribution of potentially confounding factors.

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“…To increase precision in a confounder-adjusted estimate, the matched factors should be included in the appropriate statistical models. (2)(3)(4) There are some concerns regarding matching in the Huang et al (1) study. Firstly, in their study, the authors have not clearly specified which protocol they used to match cases and control (it seems that individual matching was done).…”