南部非洲的 HIV-HBV 合并感染以及拉米夫定与替诺福韦为基础的 cART 对 HBV 结局的影响。
HIV-HBV coinfection in Southern Africa and the effect of lamivudine- versus tenofovir-containing cART on HBV outcomes.
机构信息
*Department of Global Health, Academic Medical Center of the University of Amsterdam, Amsterdam, The Netherlands; †PharmAccess Foundation, Amsterdam, The Netherlands; ‡Amsterdam Institute for Global Health and Development, Amsterdam, The Netherlands; §Department of Blood-Borne Infections, Sanquin, Amsterdam, The Netherlands; ‖Department of Medical Microbiology, Academic Medical Center of the University of Amsterdam, Amsterdam, The Netherlands; ¶Department of Molecular Medicine and Hematology, University of the Witwatersrand, Johannesburg, South Africa; #Lancet Laboratories, Johannesburg, South Africa; **Lusaka Trust Hospital, Lusaka, Zambia; ††Clinical HIV Research Unit, University of the Witwatersrand, Johannesburg, South Africa; ‡‡Muelmed Hospital, Pretoria, South Africa; and §§Department of Internal Medicine and Infectious Diseases, University Medical Center Utrecht, Utrecht, The Netherlands.
出版信息
J Acquir Immune Defic Syndr. 2013 Oct 1;64(2):174-82. doi: 10.1097/QAI.0b013e3182a60f7d.
BACKGROUND
This study assessed HIV-hepatitis B virus (HBV) coinfection in southern Africa in terms of prevalence, viral characteristics, occult HBV, and the effect of lamivudine- versus tenofovir-containing first-line combination antiretroviral treatment (cART) on HBV-related outcomes.
METHODS
A multicenter prospective cohort of HIV-infected adults in Zambia and South Africa who initiated cART. Outcomes by month 12 on cART were immunological recovery, hepatitis B surface antigen (HBsAg) loss, viral suppression, and drug resistance. We used descriptive statistics, logistic regression, and linear mixed models.
RESULTS
Of the 1087 participants, 92 were HBsAg seropositive, yielding a sample-weighted prevalence of 7.4% (95% confidence interval: 5.6 to 9.2), with 76% genotype HBV-A1. The estimated CD4 recovery on cART was similar between HIV monoinfection and HIV-HBV coinfection groups and between lamivudine- and tenofovir-treated participants. HBsAg loss was documented in 20% (4/20) of lamivudine-treated and 18% (3/17) of tenofovir-treated participants (P = 0.305). Viral suppression (HBV-DNA < 20 IU/mL) was achieved in 61.5% (16/26) of lamivudine-treated and 71.4% (15/21) of tenofovir-treated participants (P = 0.477). HBV pol sequencing demonstrated M204I (n = 3) and N236T (n = 1) resistance-associated mutations in 4 of 8 (50%) lamivudine-treated participants and none in tenofovir-treated participants. Occult HBV infection was present in 13.3% before cART, but by month 12, HBV-DNA was below the limit of detection (<15 IU/mL) in 90.5% (19/21) of lamivudine-treated and 100% (18/18) of tenofovir-treated participants (P = 0.179).
CONCLUSIONS
Tenofovir-containing first-line cART is preferred for HIV-HBV coinfection in Africa because of a superior resistance profile relative to lamivudine monotherapy. Extended follow-up will be needed to determine long-term complications of occult HBV coinfection. Improved access to HBsAg screening and tenofovir is needed.
背景
本研究评估了南部非洲的 HIV-乙型肝炎病毒（HBV）合并感染，包括流行率、病毒特征、隐匿性 HBV 以及拉米夫定和替诺福韦为基础的一线抗逆转录病毒治疗（cART）对 HBV 相关结局的影响。
方法
这是一项在赞比亚和南非进行的多中心前瞻性 HIV 感染成年患者队列研究，他们开始接受 cART。cART 治疗 12 个月时的结局包括免疫恢复、乙型肝炎表面抗原（HBsAg）丢失、病毒抑制和耐药性。我们使用描述性统计、逻辑回归和线性混合模型。
结果
在 1087 名参与者中，92 名 HBsAg 阳性，经样本加权后，HBV 感染的总体流行率为 7.4%（95%置信区间：5.6 至 9.2），其中 76%为基因型 HBV-A1。在 HIV 单感染和 HIV-HBV 合并感染组以及拉米夫定和替诺福韦治疗组之间，cART 时的 CD4 恢复估计值相似。在拉米夫定治疗的 20%（4/20）和替诺福韦治疗的 18%（3/17）参与者中观察到 HBsAg 丢失（P=0.305）。在拉米夫定治疗的 61.5%（16/26）和替诺福韦治疗的 71.4%（15/21）参与者中实现了病毒抑制（HBV-DNA <20 IU/mL）（P=0.477）。HBV pol 测序显示，在 4 例（50%）拉米夫定治疗的参与者中存在 M204I（n=3）和 N236T（n=1）耐药相关突变，而替诺福韦治疗的参与者中未发现耐药相关突变。在 cART 前，隐匿性 HBV 感染的比例为 13.3%，但在 12 个月时，拉米夫定治疗的 90.5%（19/21）和替诺福韦治疗的 100%（18/18）参与者的 HBV-DNA 低于检测下限（<15 IU/mL）（P=0.179）。
结论
替诺福韦为基础的一线 cART 是非洲 HIV-HBV 合并感染的首选治疗方法，因为与拉米夫定单药治疗相比，其耐药谱更优。需要进一步的随访来确定隐匿性 HBV 合并感染的长期并发症。需要改善 HBsAg 筛查和替诺福韦的可及性。
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