Long-term Effectiveness of Accelerated Hepatitis B Vaccination Schedule in Drug Users

Dimpy P. Shah, MD, PhD; Carolyn Z. Grimes, DrPH; Anh T. Nguyen, MD; Dejian Lai, PhD; Lu-Yu Hwang, MD


Am J Public Health. 2015;105(6):e36-e43. 

In This Article

Abstract and Introduction


Objectives We demonstrated the effectiveness of an accelerated hepatitis B vaccination schedule in drug users.

Methods We compared the long-term effectiveness of accelerated (0–1–2 months) and standard (0–1–6 months) hepatitis B vaccination schedules in preventing hepatitis B virus (HBV) infections and anti-hepatitis B (anti-HBs) antibody loss during 2-year follow-up in 707 drug users (HIV and HBV negative at enrollment and completed 3 vaccine doses) from February 2004 to October 2009.

Results Drug users in the accelerated schedule group had significantly lower HBV infection rates, but had a similar rate of anti-HBs antibody loss compared with the standard schedule group over 2 years of follow-up. No chronic HBV infections were observed. Hepatitis C positivity at enrollment and age younger than 40 years were independent risk factors for HBV infection and antibody loss, respectively.

Conclusions An accelerated vaccination schedule was more preferable than a standard vaccination schedule in preventing HBV infections in drug users. To overcome the disadvantages of a standard vaccination schedule, an accelerated vaccination schedule should be considered in drug users with low adherence. 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 drug users.


One of the most common blood-borne pathogens, hepatitis B virus (HBV), has been estimated to infect approximately 2 billion people worldwide, including 350 million who live with chronic infection.[1] From these chronic infections, approximately 15% to 40% will develop cirrhosis, liver failure, and hepatocellular carcinoma, which can lead to enormous medical expenses and loss of life.[2] These staggering numbers are reflected in the US national HBV statistics as well, with a reported prevalence of 704 000 chronic HBV infections and 4.6% exposure in the general noninstitutionalized population during 1999 to 2008.[3,4] Because of its asymptomatic progression and high infectious potential (50–100 times compared with HIV), HBV has a greater potential to spread in the population, especially in high-risk groups such as drug users.[5]

Hepatitis B vaccine has been proved to be highly immunogenic and effective in prevention of HBV infection in infants and healthy adults since its introduction in 1984. However, despite the availability of a highly efficacious vaccine, hepatitis B still remains highly prevalent in drug users. Impairment of inhibition regarding high-risk sexual behavior, sharing needles, shooting galleries, drug–sex exchanges, and the level of infection within the locality play an important role in increasing the risk of acquiring these infections in injecting and noninjecting drug users (IDUs and NIDUs).[6–8] Surprisingly, hepatitis-related awareness is low among HIV knowledgeable drug users.[9] A very high prevalence of HBV (64%) has been observed among IDUs compared with the general population.[10] With approximately 51 000 new cases of HBV infections per year, 16% are estimated to be IDUs, and unvaccinated IDUs have an incidence density ranging from 10 to 31 infections per 100 person-years.[11] Furthermore, an increasing trend of drug users who adopt noninjected routes of heroin administration has been observed in the United States and other countries since late 1980s.[12] NIDUs may consist of former injectors who may have already been infected with HIV/HCV or never injectors who may become exposed to HBV infection through unprotected sex through high-risk sex partners.[13] NIDUs may serve as a potential sexual transmission bridge between high prevalence IDUs to the low prevalence general population.[14] Although studies examining HBV infection in NIDUs are generally lacking, a study conducted in adult noninjecting heroin users in New York City (1996–2001) reported that 24% of never injectors and 49% of former injectors were infected with HBV.[13] Therefore, both IDUs and NIDUs are among the prioritized target population for immunization in the United States.

Low acceptance and adherence to the standard vaccination schedule (0, 1, 6 months) is one of the primary concerns in this unstable population. Drug users are a hard to reach and mobile population who often lack access to health care. They have multiple social, psychological, and medical needs that lead to frequent change of residence, imprisonment, or admission to a therapeutic community.[15,16] Other barriers to vaccine compliance include competing needs, poor relationships with health care providers, and lack of information or education.[17,18] In our recent hepatitis B vaccine intervention trial among not-in-treatment drug users, we identified that participants on an accelerated schedule (0, 1, 2 months) were significantly more likely to receive 3 doses of vaccine than those on the standard schedule (76% vs 66%, respectively; P < .05).[19] Moreover, these participants also had a greater anti-hepatitis B (anti-HBs; antibody to hepatitis B surface antigen) seroconversion compared with the standard schedule group at 6 months (70% vs 46%; P < .001).[20] With an earlier immune response and better adherence, the accelerated schedule seems more advantageous. Despite these encouraging results, the long-term effectiveness of this accelerated vaccination schedule remains unexamined. Because an anti-HBs level of more than 10 milli-international units per milliliter is needed to offer seroprotection against HBV, and because drug users develop a suboptimal immune response following hepatitis B vaccination (58%–77%),[21] it is imperative to examine the levels of antibody protection offered by an accelerated schedule beyond 12 months.[22]

Thus, we aimed to compare the long-term effectiveness of an accelerated vaccination schedule with a standard vaccination schedule in preventing HBV infections in cohort of 707 drug users, who were free of HIV and HBV infection at enrollment and had completed 3 doses of vaccination during our HBV vaccine intervention trial. Our secondary aim was to identify the risk factors associated with anti-HBs antibody loss and HBV infection, respectively.