Allen Kahtonna, Mesner Octavio, Ganesan Anuradha, O'Bryan Thomas A, Deiss Robert G, Agan Brian K, Okulicz Jason F
Infectious Disease Clinical Research Program, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
Infectious Disease Service, San Antonio Military Medical Center, Fort Sam Houston, TX, USA.
BMC Infect Dis. 2015 May 1;15:203. doi: 10.1186/s12879-015-0937-5.
Hepatitis B virus (HBV) vaccine antibody response has been associated with reduced risk of AIDS or death. However, it is unknown whether HBV vaccine responsiveness is associated with improved immune reconstitution during treatment with combination antiretroviral therapy (cART). We evaluated the relationship between HBV vaccine response status and CD4 reconstitution on cART in the U.S Military HIV Natural History Study.
Participants with viral load <400 copies/mL within 1 year on initial cART and documented HBV vaccination and surface antibody (anti-HBs) prior to cART were included. Participants were characterized as HBV vaccine responders (anti-HBs ≥10 IU/L) or non-responders (<10 IU/L) and further divided into 2 groups based on vaccine administration before or after HIV diagnosis. Linear mixed regression was used to model CD4 reconstitution during the first year of cART.
Of the 307 and 169 participants vaccinated before or after HIV diagnosis, HBV vaccine response occurred in 288 (94%) and 74 (44%), respectively. For those vaccinated before HIV diagnosis, CD4 counts increased by a median 190 [IQR 99-310] cells/mm(3) for responders and 186 [IQR 116-366] cells/mm(3) for non-responders during the first year (P = 0.684). Participants vaccinated after HIV diagnosis had median increases of 185 [IQR 76-270] and 143 [IQR 47-238] cells/mm(3) for responders and non-responders, respectively (P = 0.134). In contrast to those with CD4 > 350 cells/mm(3) at cART initiation, participants with CD4 < 200 and 200-350 cells/mm(3) had significantly reduced CD4 gains in both groups by longitudinal mixed models, but there was no difference in CD4 recovery according to HBV vaccine seroresponse.
Although HBV vaccine responsiveness is associated with a reduction in HIV disease progression, HBV vaccine responders do not achieve greater CD4 gains during the first year of cART. Additional clinical markers are needed to predict the magnitude of post-cART immune recovery.
乙肝病毒(HBV)疫苗抗体反应与艾滋病风险降低或死亡风险降低有关。然而,目前尚不清楚HBV疫苗反应性是否与联合抗逆转录病毒疗法(cART)治疗期间免疫重建改善有关。我们在美国军事HIV自然史研究中评估了HBV疫苗反应状态与cART治疗期间CD4重建之间的关系。
纳入在初始cART治疗1年内病毒载量<400拷贝/mL且有cART治疗前HBV疫苗接种及表面抗体(抗-HBs)记录的参与者。参与者被分为HBV疫苗反应者(抗-HBs≥10 IU/L)或无反应者(<10 IU/L),并根据HIV诊断前后的疫苗接种情况进一步分为两组。采用线性混合回归模型对cART治疗第一年期间的CD4重建进行建模。
在HIV诊断前或诊断后接种疫苗的307名和169名参与者中,HBV疫苗反应分别发生在288名(94%)和74名(44%)参与者中。对于HIV诊断前接种疫苗的参与者,第一年期间反应者的CD4计数中位数增加了190[四分位间距99 - 310]个细胞/mm³,无反应者增加了186[四分位间距116 - 366]个细胞/mm³(P = 0.684)。HIV诊断后接种疫苗的参与者中,反应者和无反应者的CD4计数中位数分别增加了185[四分位间距76 - 270]和143[四分位间距47 - 238]个细胞/mm³(P = 0.134)。与cART治疗开始时CD4>350个细胞/mm³的参与者相比,CD4<200和200 - 350个细胞/mm³的参与者在两组中通过纵向混合模型的CD4增加量均显著降低,但根据HBV疫苗血清反应的CD4恢复情况没有差异。
虽然HBV疫苗反应性与HIV疾病进展的降低有关,但HBV疫苗反应者在cART治疗的第一年期间CD4增加量并未更大。需要额外的临床标志物来预测cART治疗后免疫恢复的程度。