Accelerated HBV Vaccination Schedule in Drug Users
Accelerated HBV Vaccination Schedule in Drug Users
Important conclusions can be drawn from our study, which was aimed at comparing the long-term effectiveness of accelerated and standard hepatitis B vaccine schedules in drug users. Compared with a standard vaccination schedule, drug users in an accelerated schedule had improved adherence and a significantly lower incidence of HBV infection, despite no significant difference in the rates of anti-HBs antibody loss during the 2-year follow-up.
Compared with the general population, which has excellent response rates to HBV vaccinations, drug users have suboptimal antibody response. The incidence of antibody loss during the follow-up period was not significantly different between the 2 vaccination schedules. To our knowledge, ours was the first study to examine the rate of antibody loss for a follow-up period of 2 years following HBV vaccination by an accelerated schedule. Therefore, we did not have comparative rates of antibody loss for this schedule from the literature. Loss of seroprotective antibody levels was not significantly associated with any host characteristics, except for age. Drug users aged 40 years or older were significantly less likely to lose seroprotection following HBV vaccination compared with younger vaccinated drug users. This was in contrast to a decreased seroprotection achievement by older drug users, as reported by previous studies. Thus, it could be speculated that although achieving seroprotection is difficult with increasing age, seroprotection was probably long term when achieved at an older age and less likely to be lost because of immune maturity. Increasing age is an important factor in immune response to HBV vaccination and should be examined further.
We observed a significantly lower incidence of HBV infection rates in the group that received vaccines per the accelerated schedule compared with the standard schedule. This might be explained by the fact that most of the drug users in the standard vaccination schedule were identified as infected at the 6-month follow-up visit, when they had not yet completed their third vaccine dose and developed a seroprotective immune response. The long time required for completion of vaccine doses according to the standard schedule that led to a delayed seroprotective immune response, coupled with continued exposure to HBV infection because of their high-risk behavior, made the accelerated vaccination schedule an ideal choice for vaccinating the drug-using population.
The Breslow-Wilcoxon-Gehan test demonstrated a statistically significant difference in the HBV infection rate between the 2 vaccination schedules (P = .043), but the Cox proportional hazards regression analysis did not show a significant difference in this risk (adjusted P = .053). The Cox proportional hazards regression model might be lacking in adequate power to adjust for various confounders, because only 10 drug users developed HBV infection over the entire study period. As per our clinical trial reports, IDUs were more likely to benefit from the accelerated schedules, but we did not observe any difference with respect to drug use factors. Similarly, no host factors were significantly associated with acquiring HBV infection, except for being HCV positive at the time of enrollment. Other studies also documented that HCV infection at enrollment might be a risk factor for lack of seroconversion following hepatitis B vaccination. This might be explained by the fact that the participant might have high-risk behaviors for acquiring HBV and HCV infections, or a compromised immune status because of HCV infection that makes them more vulnerable to developing HBV infection. We could not explore this association further because of the secondary nature of this study. Therefore, we recommend future studies to examine this. Another limitation of our study was the loss to follow-up of drug users who might have lost their seroprotection or developed HBV infection. Unfortunately, this is an unavoidable limitation for any study that examines drug users. However, there were no differences in loss to follow-up rates between the 2 vaccination schedule groups, thus minimizing a potential bias.
Compared with the general population, overall anti-HBs antibody response rate was low; however, there was adequate seroprotective response in vaccinated drug users. We observed no significant difference in terms of antibody loss between the 2 schedules, but there was significantly higher incidence of HBV infection rate in the standard vaccination group. We observed no chronic HBV carriers in either of the vaccination schedule groups. Because this is a hard-to-reach population with documented low follow-up rates and adherence to vaccination schedules, an accelerated schedule might be more beneficial in this population. An accelerated schedule might help prevent HBV infections by completing 3 doses of vaccination earlier, unlike the standard schedule, in which an adequate seroprotective immune response might not be achieved until 6 months. A shorter schedule would also ensure better compliance rates in this difficult to follow-up population. In addition, if the participants are available at 6 months follow-up, a booster dose might be given at 6 months if a waning immune response is observed. An accelerated HB vaccination schedule was recommended in alcoholic patients and hemodialysis patients. An accelerated vaccination schedule in drug users would be one of the steps to decrease HBV infection and transmission in this high-risk population, who are still reported to have the highest rates of HBV infection despite availability of an effective vaccine. Because drug users do not have normal immune response to HBV vaccine, more immunogenic vaccines are needed. Addition of vaccine adjuvants, such as the immunostimulatory DNA sequence, might be one of the possible mechanisms to increase the immunogenicity of HBV vaccines and thus reduce the number of required doses. A recent review demonstrated that 1018 immunostimulatory DNA sequence plus recombinant HBsAg was safe and successful in the vaccine-hyporesponsive population. Another possible solution to increase the response rates and antibody titers in drug users could be the administration of 4 intramuscular or intradermal HBV vaccine double doses at 0, 1, 2, and 6 months, a strategy similar to that reported in HIV-infected adults. These methods should be further evaluated in the drug-using population.
An accelerated HBV vaccination schedule might be more preferable than a standard vaccination schedule in preventing HBV infections in drug users. Because compliance of a longer time period and continued high-risk behavior during that time were the 2 disadvantages involved with the standard vaccination schedule, we recommend the accelerated vaccination schedule as a potential solution in the drug-using population. Our study should be repeated in different cohorts to validate our findings and establish the role of an accelerated schedule in hepatitis B vaccination guidelines for this high-risk population.
Discussion
Important conclusions can be drawn from our study, which was aimed at comparing the long-term effectiveness of accelerated and standard hepatitis B vaccine schedules in drug users. Compared with a standard vaccination schedule, drug users in an accelerated schedule had improved adherence and a significantly lower incidence of HBV infection, despite no significant difference in the rates of anti-HBs antibody loss during the 2-year follow-up.
Compared with the general population, which has excellent response rates to HBV vaccinations, drug users have suboptimal antibody response. The incidence of antibody loss during the follow-up period was not significantly different between the 2 vaccination schedules. To our knowledge, ours was the first study to examine the rate of antibody loss for a follow-up period of 2 years following HBV vaccination by an accelerated schedule. Therefore, we did not have comparative rates of antibody loss for this schedule from the literature. Loss of seroprotective antibody levels was not significantly associated with any host characteristics, except for age. Drug users aged 40 years or older were significantly less likely to lose seroprotection following HBV vaccination compared with younger vaccinated drug users. This was in contrast to a decreased seroprotection achievement by older drug users, as reported by previous studies. Thus, it could be speculated that although achieving seroprotection is difficult with increasing age, seroprotection was probably long term when achieved at an older age and less likely to be lost because of immune maturity. Increasing age is an important factor in immune response to HBV vaccination and should be examined further.
We observed a significantly lower incidence of HBV infection rates in the group that received vaccines per the accelerated schedule compared with the standard schedule. This might be explained by the fact that most of the drug users in the standard vaccination schedule were identified as infected at the 6-month follow-up visit, when they had not yet completed their third vaccine dose and developed a seroprotective immune response. The long time required for completion of vaccine doses according to the standard schedule that led to a delayed seroprotective immune response, coupled with continued exposure to HBV infection because of their high-risk behavior, made the accelerated vaccination schedule an ideal choice for vaccinating the drug-using population.
Limitations
The Breslow-Wilcoxon-Gehan test demonstrated a statistically significant difference in the HBV infection rate between the 2 vaccination schedules (P = .043), but the Cox proportional hazards regression analysis did not show a significant difference in this risk (adjusted P = .053). The Cox proportional hazards regression model might be lacking in adequate power to adjust for various confounders, because only 10 drug users developed HBV infection over the entire study period. As per our clinical trial reports, IDUs were more likely to benefit from the accelerated schedules, but we did not observe any difference with respect to drug use factors. Similarly, no host factors were significantly associated with acquiring HBV infection, except for being HCV positive at the time of enrollment. Other studies also documented that HCV infection at enrollment might be a risk factor for lack of seroconversion following hepatitis B vaccination. This might be explained by the fact that the participant might have high-risk behaviors for acquiring HBV and HCV infections, or a compromised immune status because of HCV infection that makes them more vulnerable to developing HBV infection. We could not explore this association further because of the secondary nature of this study. Therefore, we recommend future studies to examine this. Another limitation of our study was the loss to follow-up of drug users who might have lost their seroprotection or developed HBV infection. Unfortunately, this is an unavoidable limitation for any study that examines drug users. However, there were no differences in loss to follow-up rates between the 2 vaccination schedule groups, thus minimizing a potential bias.
Compared with the general population, overall anti-HBs antibody response rate was low; however, there was adequate seroprotective response in vaccinated drug users. We observed no significant difference in terms of antibody loss between the 2 schedules, but there was significantly higher incidence of HBV infection rate in the standard vaccination group. We observed no chronic HBV carriers in either of the vaccination schedule groups. Because this is a hard-to-reach population with documented low follow-up rates and adherence to vaccination schedules, an accelerated schedule might be more beneficial in this population. An accelerated schedule might help prevent HBV infections by completing 3 doses of vaccination earlier, unlike the standard schedule, in which an adequate seroprotective immune response might not be achieved until 6 months. A shorter schedule would also ensure better compliance rates in this difficult to follow-up population. In addition, if the participants are available at 6 months follow-up, a booster dose might be given at 6 months if a waning immune response is observed. An accelerated HB vaccination schedule was recommended in alcoholic patients and hemodialysis patients. An accelerated vaccination schedule in drug users would be one of the steps to decrease HBV infection and transmission in this high-risk population, who are still reported to have the highest rates of HBV infection despite availability of an effective vaccine. Because drug users do not have normal immune response to HBV vaccine, more immunogenic vaccines are needed. Addition of vaccine adjuvants, such as the immunostimulatory DNA sequence, might be one of the possible mechanisms to increase the immunogenicity of HBV vaccines and thus reduce the number of required doses. A recent review demonstrated that 1018 immunostimulatory DNA sequence plus recombinant HBsAg was safe and successful in the vaccine-hyporesponsive population. Another possible solution to increase the response rates and antibody titers in drug users could be the administration of 4 intramuscular or intradermal HBV vaccine double doses at 0, 1, 2, and 6 months, a strategy similar to that reported in HIV-infected adults. These methods should be further evaluated in the drug-using population.
Conclusions
An accelerated HBV vaccination schedule might be more preferable than a standard vaccination schedule in preventing HBV infections in drug users. Because compliance of a longer time period and continued high-risk behavior during that time were the 2 disadvantages involved with the standard vaccination schedule, we recommend the accelerated vaccination schedule as a potential solution in the drug-using population. Our study should be repeated in different cohorts to validate our findings and establish the role of an accelerated schedule in hepatitis B vaccination guidelines for this high-risk population.
