Assessing the Response to Hepatitis B Immunizations in HIV-Positive Adults: Results from the 550 Clinic cohort study Camila Calderon 1, Anupama Raghuram 1, Timothy Weimken 1, Robert Kelley 1, Paula Peyrani 1, Diana Otero 1,Julio Ramirez 1 1 Division of Infectious Diseases, University of Louisville, Louisville, KY ABSTRACT REFERENCES RESULTS, CONTINUED Background: HIV and hepatitis B (HBV) coinfection often leads to increased risk of chronic complication, rendering screening and prevention of HBV essential. In this study, we analyzed the rates of seroconversion after HBV vaccination series and possible predictors of response to immunization. Methods: This was a retrospective, observational study of HIV patients followed at the University of Louisville 550 Clinic from January 2000 to December Demographic data, CD4 count and HIV viral load (VL) at the time of initial vaccination series, total number of vaccine doses received and post-vaccination titers were documented. The response to the initial and re-vaccination series (anti-HBs titer ≥ 10 IU/L), was analyzed by using Chi-squared or Fisher’s exact test. Results: A total of 235 patients were included in the analysis; 68% received HBV vaccination. From the 102 patients with post-vaccination antibody titers, 50.9% responded to immunization. Eighty-six percent of the non-responders were revaccinated. Post-revaccination titers were available for 8 patients, 7/8 responded. Median CD4 counts were higher and VL lower in responders; these correlations were not statistically significant. Female gender, age >40 and receipt of ≥ 3 doses of HBV vaccine were inversely associated with response to immunization (p=0.04, p=0.01 and p<0.0001, respectively). Conclusions: The rate of seroconversion following HBV immunization in our HIV study population was 50.9%, a considerably lower response than observed in immunocompetent patients (95%). Recommendations for HBV vaccination and assessment of response in HIV patients are not well defined in the literature. Enhanced post-vaccination titer surveillance, utilization of high-dose vaccine and aggressive revaccination may be required in this population. Additional, prospective trials are needed to determine novel approaches to HBV immunization in HIV positive patients. INTRODUCTION Study design and population: This was a retrospective, observational study of HIV patients followed at the University of Louisville 550 Clinic from January 2000 to December The 550 clinic (formerly WINGS) has been serving HIV positive patients for the past 15 years and currently has over 1,600 patients enrolled in care. Study variables: Demographic data, CD4 count and HIV viral load (VL) at the time of initial vaccination series, total number of vaccine doses received and post-vaccination titers were documented. Statistical analysis: The response to the initial and re-vaccination series (anti-HBs titer ≥ 10 IU/L), was analyzed by using Chi-squared or Fisher’s exact test. RESULTS A total of 235 patients were included in the initial analysis. The distribution of responders and non- responders in our population is shown in figure 1. Baseline patient demographics, risk factors for HIV, median CD4 count, median VL and median age of responders and non- responders to HBV immunization are shown in table 1. Selected demographic characteristics of responders and non-responders to HBV vaccination are shown in figure 2. Of the risk factors analyzed, age > 40 and female sex were significantly associated with a lack of response to vaccination (p= 0.01 and p=0.04, respectively). The relationship between immune status, age and number of doses of HBV vaccine in responders and non- responders to HBV immunization are shown in figure 3. Eighty- seven percent of patients received 3 or more standard doses of HBV vaccine. This factor was significantly associated with unresponsiveness to immunization (p<0.0001). The average CD4 was higher and VL lower in the group of responders compared to non- responders, although these correlations were not statistically significant. Figure 1: Flow chart of responders and non- responders to HBV immunization Table 1: Demographic characteristics of HIV population- responders and non- responders to HBV immunization Figure 2: Relationships between immune status, age and number of doses of HBV vaccine received in responders and non- responders to HBV immunization Figure 2: Selected demographic characteristics of responders and non- responders to HBV immunization. CONCLUSIONS  The rate of seroconversion following HBV immunization in our HIV population was 50.9%, considerably lower than that reported in immunocompetent patients (95%). 1  Males responded better to HBV immunization in our study, contrary to what has been described in other publications. The mechanism of gender response to HBV immunization remains poorly understood.  Subjects younger than 40 years of age responded better to HBV immunization in our population, as has been previously described in the literature. 11  Receipt of 3 or more doses of HBV immunization was linked to lack of response to HBV vaccination. This finding could indicate that non- responders will remain so despite repeated efforts to immunize them. Our current use of standard dose HBV vaccination may have implications in the vaccine response in our population.  Enhanced post- vaccination surveillance, aggressive re-vaccination and utilization of high dose vaccine may be required in this population.  Additional, larger prospective trials are needed to determine novel approaches to HBV immunization in HIV positive patients. 1. Strategies to increase responsiveness to hepatitis B vaccination in adults with HIV-1. Whitaker et al. Lancet Infect Dis 2012; 12: A Randomized Controlled Study of Accelerated Versus Standard Hepatitis B Vaccination in HIV-Positive Patients. Vries- Sluijs et al. JID 2011;203:984–91 3. Efficacy of Double-Dose Hepatitis B Rescue Vaccination in HIV-Infected Patients. Psevdos et al. AIDS Patient Care and STDs Volume 24, Number 7, High rates of serological response to a modified hepatitis B vaccination schedule in HIV- infected adults subjects. Potsch et al. Vaccine 28 (2010) 1447– Serologic response to hepatitis B vaccine with high dose and increasing number of injections in HIV infected adult patients. Cruciani et al. Vaccine 27 (2009) 17–22 6.A Prospective Open Study of the Efficacy of High-Dose Recombinant Hepatitis B Rechallenge Vaccination in HIV-Infected Patients. Vries-Sluijs et al. JID 2008; 197:292– 4 7.Randomized trial of recombinant hepatitis B vaccine in HIV-infected adult patients comparing a standard dose to a double dose. Fonseca et al. Vaccine 23 (2005) 2902– Impact of a new vaccine clinic on hepatitis B vaccine completion and immunological response rates in an HIV-positive cohort. Rock et al. Journal of Infection and Public Health (2013) 6, 173—178 9.Vaccination against hepatitis B with 4-double doses increases response rates and antibodies titers in HIV-infected adults. Potsch et al. Vaccine 30 (2012) 5973– Long-term response rates of successful hepatitis B vaccination in HIV-infected patients. Lopes et al. Vaccine 31 (2013) 1040– Assessing the immunological response to hepatitis B vaccination in HIV-infected patients in clinical practice. Mena et al. Vaccine 30 (2012) 3703–3709. HIV and hepatitis B (HBV) co-infection often leads to an increased risk of chronic infection, end- stage liver disease and hepatocellular carcinoma. HIV infected patients are, in addition, less likely to clear acute HBV infection. The similar routes of transmission for both infections have rendered screening and prevention of HBV a cornerstone of the routine medical management of HIV positive populations. The response to routine, standard dose HBV immunization schedules has been notoriously lower in HIV positive patients compared to their immunocompetent counterparts. 3,5,11 Recommendations for HBV vaccination, assessment of response and revaccinations in this population are not well defined in the literature. 1 The description of factors associated with enhanced response to HBV immunization in HIV positive patients has been an area of interest for researchers. Female gender, age 200 and well controlled VL have been linked to better response to HBV immunization in this population. 1,2,3,5,7,9,11 In our retrospective cohort study, we sought to analyze the rates of seroconversion after initial HBV vaccination series and possible predictors of response to immunization. MATERIALS AND METHODS