Background: Outbreaks of hepatitis A virus (HAV) infection have reemerged among men who have sex with men (MSM) across the Asia-Pacific region, the United States, and several European countries since 2015. The suboptimal response to HAV vaccine among MSM living with HIV raises serious concerns about the personal-level and population-level effectiveness of HAV vaccination. We estimated the transmissibility of HAV during an hepatitis A outbreak among MSM living with HIV in Taiwan, 2015-2017, and measured the effectiveness of HAV vaccine in this population.
Methods: We developed a mathematical model of HAV transmission to estimate the basic reproductive number (R0) of HAV in this outbreak. A case of acute hepatitis A was defined as a documented positive anti-HAV IgM in an HIV-positive patient who presented with clinical symptoms, elevated aminotransferases, or jaundice. We conducted a 1:4 nested case-control study to assess the effectiveness of HAV vaccine in MSM living with HIV.
Results: Given 30% of HIV-positive patients having mild symptoms after acquiring acute hepatitis A, we estimated the R0 of HAV was as high as 6.37 in this outbreak. During study period (from June 1, 2015 to June 30, 2017), 55 cases of acute hepatitis A occurred among 1533 initially HAV seronegative HIV-positive patients. All case patients were MSM with a median age of 30 years and baseline CD4 count of 545 cells/µL, and 60% had recent syphilis within 6 months prior to the onset of acute hepatitis A. HAV vaccination protected recipients from acute hepatitis A (adjusted odds ratio, 0.03; 95% CI, 0.001-0.12), with an overall vaccine effectiveness of 97.4% (Table). The effectiveness of single dose and two doses of HAV vaccine was 96.1% and 99.7%, respectively. This high personal-level vaccine effectiveness in MSM living with HIV might explain the rapid control of this hepatitis A outbreak in Taiwan (Figure).
Conclusions: Our findings strongly support the implementation of HAV vaccination to control hepatitis A outbreak among MSM living with HIV.

 Univariable analysisMultivariable analysis
 Odds ratio (95% CI)P valueOdds ratio (95% CI)P value
At least one dose of HAV vaccination0.04 (0.01-0.13)<0.0010.03 (0.001-0.12)<0.001
Age, per 1-year increase1.53 (0.63-3.70)0.349  
HBsAg positivity1.28 (0.27-4.98)0.913  
Anti-HCV positivity2.03 (0.58-6.57)0.302  
Receiving cART at baseline1.19 (0.52-2.70)0.685  
CD4 count at baseline, per 1-cell/mm3 increase0.999 (0.998-1.001)0.316  
PVL at baseline, per 1-log10 copies/mL increase1.03 (0.88-1.21)0.710  
Syphilis during follow-up3.93 (2.04-7.60)<0.00113.52 (1.40-130.26)0.024
[Factors associated with acquiring acute hepatitis A]

Number of indigenous cases of acute hepatitis A reported to the Taiwan CDC during the outbreak.
[Number of indigenous cases of acute hepatitis A reported to the Taiwan CDC during the outbreak.]