Accelerated HBV Vaccination Schedule in Drug Users
Accelerated HBV Vaccination Schedule in Drug Users
The follow-up rates at each time point for 707 HBV susceptible drug users was 92% (650) at 6 months, 81% (576) at 12 months, 73% (519) at 18 months, and 67% (473) at 24 months. Baseline characteristics for this study population, stratified by the 2 vaccination schedules, were described in detail in our earlier study. These 707 participants contributed approximately 1166 person-years from the time of their enrollment. We show the outcomes for the our study population in Figure 1. A large proportion of participants did not develop the desired anti-HBs antibody level at 12-month follow-up (57% and 47%), and these nonresponders had the highest incidence of HBV infection (1 and 6 cases) in accelerated and standard schedule groups, respectively.
(Enlarge Image)
Figure 1.
Outcomes stratified by vaccination schedules: Long-Term Effectiveness of Accelerated Hepatitis B Vaccination Schedule.
Note. HBs = hepatitis B; HBV = hepatitis B virus. Data on antibody loss were not available for 14 (9%) drug users in the accelerated schedule group and 23 (13%) drug users in the standard schedule group.
Of the 339 drug users who developed an adequate seroprotective response after completion of 3 vaccine doses and were free of infection at 6 months, a total of 41 lost detectable anti-HBs antibodies, including 23 in the accelerated group and 18 in the standard group (Figure 2). The cumulative incidence of antibody loss for the entire subgroup was 20 cases per 100 drug users (cumulative incidence of antibody persistence was 80%). We could not identify any statistically significant difference for anti-HBs antibody loss between accelerated and standard vaccine schedules (22 vs 18 cases per 100 drug users, respectively; likelihood ratio test: P = .223). The geometric mean titers (GMT) were 116, 105, 58, 67, and 70 milli-international units per milliliter for the accelerated schedule and 128, 64, 185, 159 and 150 milli-international units per milliliter for the standard schedule at 2, 6, 12, 18, and 24 months, respectively. We found no significant difference between the incidence density for anti-HBs antibody loss for the accelerated and standard schedules (186 and 127 cases per 1000 person-years, respectively).
(Enlarge Image)
Figure 2.
Kaplan-Meier failure curves, stratified by vaccination schedules, for (a) hepatitis B virus (HBV) infection and (b) antibody to hepatitis B surface antigen (anti-HBs) loss: Long-Term Effectiveness of Accelerated Hepatitis B Vaccination Schedule.
Note. The sample sizes were n = 707 HBV-susceptible drug users in part a and n = 339 vaccine responders at 12 months in part b. P values were determined by Breslow–Gehan–Wilcoxon test of homogeneity.
The effects of various exposures on incidence rate of antibody loss are demonstrated in Table 1. None of the exposures listed in the Table 1 significantly predicted antibody loss, except for age. Drug users who were aged 40 years or older at enrollment had a 57% decreased incidence of antibody loss compared with those younger than 40 years (P < .05).
During the 2-year follow-up period, we detected HBV infection in 10 drug users who had completed their vaccination doses, thus giving a cumulative incidence of 2 cases per 100 drug users. Of these 10 infection cases, 8 had received vaccination according to the standard schedule compared with 2 cases who received it according to the accelerated schedule (cumulative incidence of 3 cases vs 1 case per 100 drug users, respectively). This was a statistically significant difference in the incidence of HBV infection between the 2 vaccination schedules (likelihood ratio test χ = 4; P < .05). The incidence density for the accelerated vaccination schedule (3 cases per 1000 person-years) was significantly lower than that for the standard schedule (14 cases per 1000 person-years). Incidence densities stratified for various exposures of interest are shown in Table 2. None of the exposures listed in Table 2 significantly predicted acquisition of HBV infection, except for HCV seropositivity at enrollment. Having HCV at enrollment increased the risk for acquiring HBV infection during the follow-up (adjusted risk ratio = 6.54; 95% CI = 1.49, 28.76; P = .013). Although not statistically significant, the risk for HBV infection increased by 60% for participants who did not develop protective anti-HBs level at 12 months. Similarly, the risk of HBV infection was increased by 80% when participants were vaccinated using the standard schedule compared with the accelerated schedule. Kaplan-Meier failure curves demonstrated the significant difference in cumulative incidence rate for HBV infection for the 2 vaccination schedules (P < .05 for Breslow–Gehan–Wilcoxon test; Figure 2).
A detailed description for 10 HBV infected drug users including age, gender, vaccination schedule, anti-HBc test results, and anti-HBs status at 12 months is provided in Table 3. The majority of these users were male (80%), aged 40 years or older (70%), had 12 month anti-HBs levels less than 10 milli-international units per milliliter (70%), received vaccination according to the standard schedule (80%), and acquired HBV infection by 6 months of enrollment (60%). HBsAg was detected in 2 cases, with both the vaccination groups having 1 case each. No chronic infection was identified in either of the vaccination schedule groups over the 2-year period.
Results
The follow-up rates at each time point for 707 HBV susceptible drug users was 92% (650) at 6 months, 81% (576) at 12 months, 73% (519) at 18 months, and 67% (473) at 24 months. Baseline characteristics for this study population, stratified by the 2 vaccination schedules, were described in detail in our earlier study. These 707 participants contributed approximately 1166 person-years from the time of their enrollment. We show the outcomes for the our study population in Figure 1. A large proportion of participants did not develop the desired anti-HBs antibody level at 12-month follow-up (57% and 47%), and these nonresponders had the highest incidence of HBV infection (1 and 6 cases) in accelerated and standard schedule groups, respectively.
(Enlarge Image)
Figure 1.
Outcomes stratified by vaccination schedules: Long-Term Effectiveness of Accelerated Hepatitis B Vaccination Schedule.
Note. HBs = hepatitis B; HBV = hepatitis B virus. Data on antibody loss were not available for 14 (9%) drug users in the accelerated schedule group and 23 (13%) drug users in the standard schedule group.
Anti-hepatitis B Antibody Loss and Persistence
Of the 339 drug users who developed an adequate seroprotective response after completion of 3 vaccine doses and were free of infection at 6 months, a total of 41 lost detectable anti-HBs antibodies, including 23 in the accelerated group and 18 in the standard group (Figure 2). The cumulative incidence of antibody loss for the entire subgroup was 20 cases per 100 drug users (cumulative incidence of antibody persistence was 80%). We could not identify any statistically significant difference for anti-HBs antibody loss between accelerated and standard vaccine schedules (22 vs 18 cases per 100 drug users, respectively; likelihood ratio test: P = .223). The geometric mean titers (GMT) were 116, 105, 58, 67, and 70 milli-international units per milliliter for the accelerated schedule and 128, 64, 185, 159 and 150 milli-international units per milliliter for the standard schedule at 2, 6, 12, 18, and 24 months, respectively. We found no significant difference between the incidence density for anti-HBs antibody loss for the accelerated and standard schedules (186 and 127 cases per 1000 person-years, respectively).
(Enlarge Image)
Figure 2.
Kaplan-Meier failure curves, stratified by vaccination schedules, for (a) hepatitis B virus (HBV) infection and (b) antibody to hepatitis B surface antigen (anti-HBs) loss: Long-Term Effectiveness of Accelerated Hepatitis B Vaccination Schedule.
Note. The sample sizes were n = 707 HBV-susceptible drug users in part a and n = 339 vaccine responders at 12 months in part b. P values were determined by Breslow–Gehan–Wilcoxon test of homogeneity.
The effects of various exposures on incidence rate of antibody loss are demonstrated in Table 1. None of the exposures listed in the Table 1 significantly predicted antibody loss, except for age. Drug users who were aged 40 years or older at enrollment had a 57% decreased incidence of antibody loss compared with those younger than 40 years (P < .05).
Hepatitis B Virus Infection
During the 2-year follow-up period, we detected HBV infection in 10 drug users who had completed their vaccination doses, thus giving a cumulative incidence of 2 cases per 100 drug users. Of these 10 infection cases, 8 had received vaccination according to the standard schedule compared with 2 cases who received it according to the accelerated schedule (cumulative incidence of 3 cases vs 1 case per 100 drug users, respectively). This was a statistically significant difference in the incidence of HBV infection between the 2 vaccination schedules (likelihood ratio test χ = 4; P < .05). The incidence density for the accelerated vaccination schedule (3 cases per 1000 person-years) was significantly lower than that for the standard schedule (14 cases per 1000 person-years). Incidence densities stratified for various exposures of interest are shown in Table 2. None of the exposures listed in Table 2 significantly predicted acquisition of HBV infection, except for HCV seropositivity at enrollment. Having HCV at enrollment increased the risk for acquiring HBV infection during the follow-up (adjusted risk ratio = 6.54; 95% CI = 1.49, 28.76; P = .013). Although not statistically significant, the risk for HBV infection increased by 60% for participants who did not develop protective anti-HBs level at 12 months. Similarly, the risk of HBV infection was increased by 80% when participants were vaccinated using the standard schedule compared with the accelerated schedule. Kaplan-Meier failure curves demonstrated the significant difference in cumulative incidence rate for HBV infection for the 2 vaccination schedules (P < .05 for Breslow–Gehan–Wilcoxon test; Figure 2).
A detailed description for 10 HBV infected drug users including age, gender, vaccination schedule, anti-HBc test results, and anti-HBs status at 12 months is provided in Table 3. The majority of these users were male (80%), aged 40 years or older (70%), had 12 month anti-HBs levels less than 10 milli-international units per milliliter (70%), received vaccination according to the standard schedule (80%), and acquired HBV infection by 6 months of enrollment (60%). HBsAg was detected in 2 cases, with both the vaccination groups having 1 case each. No chronic infection was identified in either of the vaccination schedule groups over the 2-year period.
