| Objective:Identify the virological and immunological response in HIV/HBV co-infected patients after long-time of combined antiretroviral therapy(cART)and explore the dynamics of humoral and cellular response in viral-suppressed HIV-infected patients who have been immunized with a 3-dose series of hepatitis B vaccine.Methods:HIV/HBV co-infected patients included in this study were screened from two established national multicenter cohorts.The changes of HIV RNA,HBV DNA,HBV RNA and T cell subsets were detected at baseline,96 weeks and 240 weeks after cART.32 HIV-infected patients(HIV RNA<200 copies/mL and CD4>350 cells/?L for at least 24 weeks)were enrolled from the clinic of infectious diseases in Peking Union Medical College Hospital.They are immunized with a 20 ?g HBV vaccine on a 0-,4-,24-week schedule.Clinical data and blood samples were collected at pre-vaccination,8 weeks after the second dose and 12-24 weeks after the last dose.Peripheral blood mononuclear cells were stimulated with recombinant HBV surface protein.IFN-r and TNF-a-secreting T cells were identified by ELISPOT assay.Results:1.A total of 132 HIV/HBV co-infected patients were included in this study.Among them,there were 100 HBeAg-negative individuals.At cART 96 and 240 weeks,the suppression rates of HBV DNA were 76.6%and 88.4%,respectively.The suppression rate of HBeAg positive patients was lower than that of HBeAg negative patients(27.8%vs 91.5%,66.7%vs 92.9%).2.Baseline HBV RNA levels were measured in 93 enrolled patients,of whom 67 were HBeAg negative and 26 were HBeAg positive.31 patients were positive for HBV RNA,and the median level was 4.87(4.19-6.1 1)lg copies/ml.Among the HBV RNA positive patients,20 were HBeAg positive,and the median HBV RNA level was 5.59(4.61-6.67)lg copies/ml.11 patients were HBeAg negative,and the median HBV RNA level was 4.19(2.70-4.65)lg copies/ml.There was positive correlation between baseline HBV RNA level and HBV DNA level(r=0.385,p=0.033)and strong correlation existed between baseline HBV RNA level and HBsAg(r=0.567,p=0.002).28 patients completed 138(54-240)weeks of the follow-up,and the median HBV RNA level was 3.57(0-6.26)lg copies/ml.HBV RNA levels gradually turned negative in seven patients during the follow-up period.HBV RNA was negative in 62 patients at enrolment.37 patients completed 276(48-336)weeks of follow-up,and HBV RNA was negative at the end of follow-up.3.All patients were followed up for 695.5 person-years,and no seroconversion of HBsAg was found.13(40.63%)HBeAg positive patients had seroconversion and HBeAb during follow-up.Further analysis of HBV RNA level in patients with HBeAg seroconversion showed that HBV RNA level before treatment was 4.48(0-6.55)lg copies/ml.During the 48(48-264)weeks follow-up,HBV RNA turned negative in 6 patients.4.The suppression rates of HIV RNA were 85.51%at 96 weeks and 95.65%at cART 240 weeks.The number of CD4 cells was 397(283-556)cells/?l and 424(323-609)cells/?l,respectively.The ratio of CD4/CD8 was 0.59(0.37-0.86)and 0.66(0.48-0.93),respectively.5.Thirty-two patients completed three doses of HBV vaccination.The titer of HBsAb was 157.87(18.13-802.73)IU/ml.HBsAb was found in all the patients who completed the three doses of vaccination,and the titer was 663.07(334.39-1000)IU/ml.6.16 patients were retested for HBsAb during the follow-up period of 13.5(12-17.3)months after vaccination and the median HBsAb titer was 256.15(84.04-542.48)IU/ml.The HBsAb titer of 2 patients decreased to 2.9 IU/ml and 3.62 IU/ml.7.Before vaccination,the numbers of IFN-r and TNF-? secreting cells were 30(7-73)SFC/105 PBMC,110(72-181)SFC/105 PBMC.The number of IFN-r secreting cells in two months after the second dose and in three to six months after the third dose were 53(14-129)SFC/105 PBMC,15(6-94)SFC/105 PBMC,respectively.The numbers of TNF-a secreting cells were 208(115-330)SFC/105 PBMC,180(78-250)SFC/105 PBMC,respectively.Conclusions:1.The positive rate of HBV RNA and HBV RNA level in HBeAg positive HIV/HBV co-infected patients before treatment were higher than that in HBeAg negative patients.During the long-term follow-up,the HBeAg positive HBV RNA was still at a high level.There was no correlation between baseline HBV RNA level and HBV DNA level.2.In the long-term treatment,the clearance rate of HBsAg in HIV/HBV co-infected patients was low while the suppression rate of HIV RNA and the growth of CD4 cells were ideal.3.HBsAb can be produced in HIV infected patients with stable treatment after vaccination with standard dose of HBV vaccine,but the decline rate of HBsAb is faster.4.The specific cellular immune response to HBsAg was not significantly enhanced in HIV infected patients after vaccination with HBV vaccine. |
PDF Full Text Request