Supervisors info:
Τουλούμη Παναγιώτα, Καθηγήτρια, Ιατρική, ΕΚΠΑ
Κουρκουντή Σοφία, Παθολόγος, Νοσοκομείο Α. Συγγρός
Βουρλή Γεωργία, Διδάκτωρ, Ιατρική, ΕΚΠΑ
Summary:
Background: Given the shared risk factors for transmission, co-infection of hepatitis B virus (HBV) with human immunodeficiency virus (HIV) is quite common, making liver-related diseases (mainly hepatocellular carcinoma and chronic hepatitis) important causes of morbidity and mortality in this group of patients. Ιn the era of the highly active antiretroviral therapy (HAART) immunization against HBV is highly recommended for all HIV-infected individuals without evidence of prior HBV infection or immunity. However, the classical schedule used in the general population has been shown to be insufficient in people living with HIV and several studies have been carried out, evaluating the immune response on alternative vaccination regimens and schedules.
Aims: Evaluation of a double dose (40mg) vaccination schedule against HBV in HIV positive patients who are under successful antiretroviral treatment with undeteactable viral load.
Methods: Data were drawn from a cohort study of HIV-infected individuals followed in the “Andras Sygros” hospital during 2012 to 2016. Inclusion criteria were: HIV-HCV coinfection and successful (undetectable viral load) highly active antiretroviral therapy (HAART). In total, 197 patients were vaccinated, 134 of them with the standard regimen (Engerix 20mcg on months 0, 1 ,6) and 63 with a double dose (HBVaxPro 40mcg on months 0, 1, 6). Anti-HBs antibody titer were measured at 1, 12 and 24 months. Immune response was defined as anti-HBs levels≧10 mIU/mL. Anti-HBs levels were log transformed for geometric mean titer (GMT) and compared between the two vaccination groups by Wilcoxon rank-sum tests. To investigate factors that could potentially affect immune response we applied multiple logistic regression. Non linear effects of age on immune response as well interactions between age and vaccine group were also investigated. All statistical analyses were conducted using STATA software version 11.
Results: The overall vaccine response at first month was 72% being 79.4% in the HBVaxPro group and 68.7% in the Engerix group (p=0.118). At 1 and 2 years after vaccination the corresponding percentages were 65.1% vs 53% (p = 0.110) and 47.6% vs 39.6% (p = 0.285). Anti-HBs levels were on average higher among responders receiving the double vaccine dose compared to those receiving the standard dose in all investigated time points. The adjusted for age OR of immune response was 2.2 (95% CI: 1.03- 4.6; p=0.041) in favor of double dose vaccination. Among all tested covariables (age, CD4 count, nadir CD4/history of opportunistic infection, CD4/CD8 ratio, base of HAART, BMI, smoking status, sex), age was the only one found to significantly correlate with immune response (OR= 0.958 per year, p=0.016).Further analysis revealed that the association of the odds of immune response with age was not linear and, in addition, a significant interaction between age and vaccine groups was found. The superiority of double dose vaccination compared to the standard dose decreased with age for up to 55 years, although the difference remained statistically significant up to this age, but there were no significant differences after the age of 55 years. A subgroup analysis including only patients younger than 55 years old (Ν=171) showed an overall OR of immune response when comparing double dose with standard dose of vaccination equal to 3.6 (95% CI: 1.45-9; p=0.006).
Conclusion:
A vaccination schedule with three doses of 40mcg HBVaxPRO seems to achieve better response rates and higher titer levels compared to classical one of 20mg among a population of HIV infected patients with undetectable HIV viral load. This regimen may be a favored alternate for the effective immunization of these patients.
Keywords:
HIV, HBV, Hepatitis B, Vaccination, Vaccine
