HIV病毒控制者的乙肝疫苗反应性及临床结局
Hepatitis B vaccine responsiveness and clinical outcomes in HIV controllers.
作者信息
Okulicz Jason F, Mesner Octavio, Ganesan Anuradha, O'Bryan Thomas A, Deiss Robert G, Agan Brian K
机构信息
Infectious Disease Clinical Research Program, Uniformed Services University of the Health Sciences, Bethesda, Maryland, United States of America; Infectious Disease Service, San Antonio Military Medical Center, San Antonio, Texas, United States of America.
Infectious Disease Clinical Research Program, Uniformed Services University of the Health Sciences, Bethesda, Maryland, United States of America.
出版信息
PLoS One. 2014 Aug 21;9(8):e105591. doi: 10.1371/journal.pone.0105591. eCollection 2014.
BACKGROUND
Hepatitis B virus (HBV) vaccine responsiveness is associated with reduced risk of AIDS or death in HIV-infected individuals. Although HIV controllers (HIC) typically have favorable immunologic and clinical characteristics compared to non-controllers, vaccine responsiveness has not been studied.
METHODS AND FINDINGS
In the U.S. Military HIV Natural History Study, HBV vaccine response was defined as antibody to hepatitis B surface antigen (anti-HBs) ≥ 10 IU/L after last vaccination. For determination of vaccine responsiveness, HIC (n = 44) and treatment-naïve non-controllers (n = 476) were not on highly active antiretroviral therapy (HAART) when vaccinated while treated non-controllers (n = 284) received all HBV vaccine doses during viral load (VL)-suppressive HAART. Progression to AIDS or death was also compared for all HIC (n = 143) and non-controllers (n = 1566) with documented anti-HBs regardless of the timing of HBV vaccination. Positive vaccine responses were more common in HIC (65.9%) compared to HAART-naïve non-controllers (36.6%; P<0.001), but similar to non-controllers on HAART (59.9%; P = 0.549). Factors associated with vaccine response for HIC compared to HAART-naïve non-controllers include HIC status (OR 2.65, 95% CI 1.23-5.89; P = 0.014), CD4 count at last vaccination (OR 1.28, 1.15-1.45 for every 100 cells/uL; P<0.001), and number of vaccine doses administered (OR 0.56, 0.35-0.88; P = 0.011). When HIC were compared to non-controllers on HAART, only CD4 count at last vaccination was significant (OR 1.23, 1.1-1.38 for every 100 cells/uL; P<0.001). The rate of AIDS or death per 100 person/years for HIC compared to non-controllers was 0.14 (95% CI 0-0.76) versus 0.98 (95% CI 0.74-1.28) for vaccine responders and 0 (95% CI 0-2.22) versus 4.11 (95% CI 3.38-4.96) for non-responders, respectively.
CONCLUSIONS
HIC have improved HBV vaccine responsiveness compared to treatment-naïve non-controllers, but similar to those on VL-suppressive HAART. Progression to AIDS or death can be predicted by HBV vaccine responder status for non-controllers, however these events are rarely observed in HIC.
背景
乙型肝炎病毒（HBV）疫苗反应性与HIV感染者患艾滋病或死亡风险降低相关。尽管与非病毒控制者相比，HIV病毒控制者（HIC）通常具有良好的免疫和临床特征，但尚未对疫苗反应性进行研究。
方法与结果
在美国军事HIV自然史研究中，HBV疫苗反应定义为最后一次接种疫苗后乙型肝炎表面抗原抗体（抗-HBs）≥10 IU/L。为确定疫苗反应性，HIC（n = 44）和未接受过治疗的非病毒控制者（n = 476）在接种疫苗时未接受高效抗逆转录病毒治疗（HAART），而接受治疗的非病毒控制者（n = 284）在病毒载量（VL）抑制性HAART期间接种了所有HBV疫苗剂量。还比较了所有有抗-HBs记录的HIC（n = 143）和非病毒控制者（n = 1566）发生艾滋病或死亡的情况，无论HBV疫苗接种时间如何。与未接受过HAART的非病毒控制者相比，HIC的疫苗阳性反应更常见（65.9%），而未接受过HAART的非病毒控制者为36.6%（P<0.001），但与接受HAART的非病毒控制者相似（59.9%；P = 0.549）。与未接受过HAART的非病毒控制者相比，与HIC疫苗反应相关的因素包括HIC状态（比值比[OR] 2.65，95%置信区间[CI] 1.23 - 5.89；P = 0.014）、最后一次接种疫苗时的CD4细胞计数（每100个细胞/微升的OR为1.28，1.15 - 1.45；P<0.001）以及接种疫苗的剂量数（OR 0.56，0.35 - 0.88；P = 0.011）。当将HIC与接受HAART的非病毒控制者进行比较时，仅最后一次接种疫苗时的CD4细胞计数有显著差异（每100个细胞/微升的OR为1.23，1.1 - 1.38；P<0.001）。与非病毒控制者相比，HIC每100人年的艾滋病或死亡率，疫苗反应者为0.14（95% CI 0 - 0.76），而非反应者为0（95% CI 0 - 2.22）；非病毒控制者的疫苗反应者为0.98（95% CI 0.74 - 1.28），非反应者为4.11（95% CI 3.38 - 4.96）。
结论
与未接受过治疗的非病毒控制者相比，HIC的HBV疫苗反应性有所改善，但与接受VL抑制性HAART的患者相似。对于非病毒控制者，HBV疫苗反应者状态可预测艾滋病或死亡的进展，然而在HIC中很少观察到这些事件。
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