Seremba Emmanuel, Ssempijja Victor, Kalibbala Sarah, Gray Ronald H, Wawer Maria J, Nalugoda Fred, Casper Corey, Phipps Warren, Ocama Ponsiano, Serwadda David, Thomas David L, Reynolds Steven J
aSchool of Medicine, Makerere University College of Health Sciences, Kampala, Uganda bClinical Research Directorate/Clinical Monitoring Research Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA cRakai Health Sciences Program, Kalisizo, Uganda dJohns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA eFred Hutchinson Cancer Research Center and University of Washington, Seattle, Washington, USA fSchool of Public Health, Makerere University College of Health Sciences, Kampala, Uganda gJohns Hopkins University School of Medicine, Baltimore hDivision of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
AIDS. 2017 Mar 27;31(6):781-786. doi: 10.1097/QAD.0000000000001399.
Antiretroviral therapy (ART) may interfere with replication of hepatitis B virus (HBV), raising the hypothesis that HBV infection might be prevented by ART. We investigated the incidence and risk factors associated with HBV among HIV-infected adults in Rakai, Uganda.
We screened stored sera from 944 HIV-infected adults enrolled in the Rakai Community Cohort Study between September 2003 and March 2015 for evidence of HBV exposure. Serum from participants who tested anti-hepatitis B core-negative (497) at baseline were tested over 3-7 consecutive survey rounds for incident HBV. Poisson incidence methods were used to estimate incidence of HBV with 95% confidence intervals (CIs), whereas Cox proportional regression methods were used to estimate hazard ratios (HRs).
Thirty-nine HBV infections occurred over 3342 person-years, incidence 1.17/100 person-years. HBV incidence was significantly lower with ART use: 0.49/100 person-years with ART and 2.3/100 person-years without ART [adjusted HR (aHR) 0.25, 95% CI 0.1-0.5, P < 0.001], and with lamivudine (3TC) use: 0.58/100 person-years) with 3TC and 2.25/100 person-years without 3TC (aHR 0.32, 95% CI 0.1-0.7, P = < 0.007). No new HBV infections occurred among those on tenofovir-based ART. HBV incidence also decreased with HIV RNA suppression: 0.6/100 person-years with 400 copies/ml or less and 4.0/100 person-years with more than 400 copies/ml (aHR, 6.4, 95% CI 2.2-19.0, P < 0.001); and with age: 15-29 years versus 40-50 years (aHR 3.2, 95% CI 1.2-9.0); 30-39 years versus 40-50 years (aHR 2.1, 95% CI 0.9-5.3).
HBV continues to be acquired in adulthood among HIV-positive Ugandans and HBV incidence is dramatically reduced with HBV-active ART. In addition to widespread vaccination, initiation of ART may prevent HBV acquisition among HIV-positive adults in sub-Saharan Africa.
抗逆转录病毒疗法(ART)可能会干扰乙型肝炎病毒(HBV)的复制,由此提出ART可能预防HBV感染的假说。我们调查了乌干达拉凯地区HIV感染成人中HBV的发病率及相关危险因素。
我们对944名于2003年9月至2015年3月参加拉凯社区队列研究的HIV感染成人的储存血清进行筛查,以寻找HBV暴露的证据。对基线时抗乙肝核心抗体检测为阴性(497例)的参与者的血清,在连续3 - 7轮调查中检测新发HBV感染情况。采用泊松发病率方法估计HBV发病率及95%置信区间(CI),采用Cox比例回归方法估计风险比(HR)。
在3342人年中发生了39例HBV感染,发病率为1.17/100人年。使用ART时HBV发病率显著降低:使用ART时为0.49/100人年,未使用ART时为2.3/100人年[调整后HR(aHR)0.25,95%CI 0.1 - 0.5,P<0.001];使用拉米夫定(3TC)时:使用3TC时为0.58/100人年,未使用3TC时为2.25/100人年(aHR 0.32,95%CI 0.1 - 0.7,P =<0.007)。在基于替诺福韦的ART治疗者中未发生新的HBV感染。HBV发病率也随着HIV RNA抑制而降低:HIV RNA低于400拷贝/ml时为0.6/100人年,高于400拷贝/ml时为4.0/100人年(aHR 6.4,95%CI 2.2 - 19.0,P<0.001);随着年龄降低:15 - 29岁与40 - 50岁相比(aHR 3.2,95%CI 1.2 - 9.0);30 - 39岁与40 - 50岁相比(aHR 2.1,95%CI 0.9 - 5.3)。
在乌干达HIV阳性的成年人中,成年期仍会感染HBV,而使用抗HBV活性的ART可显著降低HBV发病率。除广泛接种疫苗外,启动ART可能预防撒哈拉以南非洲HIV阳性成年人感染HBV。