| Objective:The international society recommends that HIV infected patients without HBV infection should get vaccinated.But no such research had been carried out in Chinese PLWH.We aimed to investigate the long-term effectiveness of neonatal vaccination against hepatitis B in HIV infected patients.Meanwhile,to explore the efficacy and safety of routine HBV vaccine in Chinese PLWH and possibly find some clues about the optimal vaccination schedules for this population.Methods:18-25-year-old HIV infected patients from the 12th 5-year-plan of National Science and Technology Major Project were included,all born after the implementation of routine HBV vaccine for infants.Positive rates of HBsAg,HBcAb and HBsAb in this population were cross-sectionally researched and compared with those in age-matched healthy people.Furthermore,HIV infected patients with consistent viral suppression and well-reconstituted immune state(CD4+counts>350/?L)were screened for HBV and HCV infection.Those negative for HBsAg,HBsAb,HBeAg,HBeAb,HBcAb and HCV antibodies were vaccinated with 20?g of recombinant HBV vaccine at 0,1,6 months.HBsAb titers were measured at month 3 and 9.Blood samples were also collected at month 0(before vaccination),3 and 9 and PBMCs were subtracted for further analysis.Flow cytometry was used to detect change of T lymphocyte subsets and cytokine secretion specific for HBsAg stimulation was detected through ELISpot.Results:1.The number of participants enrolled was 171.The average positive rates of HBsAg,HBcAb were 4.1%(95%CI:1-7.1%)and 14.6%(95%CI:9.3-20.0%),respectively.59 patients were positive for HBsAb,resulting in a positive rate of 34.5%(95%CI:27.3-41.7%).Compared with age-matched healthy population,no significant difference was found.2.i)Till May 2019,a total of 14 eligible patients finished 2 doses of HBV vaccine.8(57.1%)patients developed anti-HBs titers above 10 mIU/mL,6 of whom were hyper-responsive defined as HBsAb>100 mIU/mL L.It turned out that elder patients(r=-0.700,P=0.005)and those more profoundly immune activated(r=-0.609,p=0.021)were harder to develop HBV antibodies after vaccination.No severe adverse events were reported.No viral rebound or decrease of CD4+ counts were detected in all patients.ii)In responders,the CD4+and CD8+cell subsets displayed more mature profiles after vaccination,i.e.the proportion of naive cells decreased and that of TEM increased significantly.Meanwhile,the non-responders only showed alike trend but no significant results were found.Despite vaccination with T-cell dependent immunogens,the proportion of activation subsets marked as CD38+ cells decreased compared with baseline in both groups.After 24 hours of stimulation of rHBsAg(5?g/mL),CD4+Tcm subsets of the responders expanded significantly while CD4+TEM subsets shrunk.Similar trend was observed in CD8+T cell subsets except that only change of CD8+Tcm reached significance.On the other hand,non-responders displayed no substantial change.iii)After vaccination,enhancement of IFN-y and TNF-a secretion specific to HBsAg stimulation was detected in neither group.Longer follow-up may be needed to detect the development of specific cell-mediated immune response.Conclusions:1.The long-term efficacy of neonatal vaccination against HBV seems not compromised in HIV patients with infection duration around 1 year.2.For HIV infected patients with sustained viral suppression and well-reconstituted immune state,HBV vaccine is safe and rather effective to elicit protective immune response. |
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