Institute for Global Health, University College London, London, United Kingdom.
MRC Clinical Trials Unit, University College London, London, United Kingdom.
J Acquir Immune Defic Syndr. 2021 Jan 1;86(1):98-103. doi: 10.1097/QAI.0000000000002517.
WHO treatment guidelines recommend tenofovir plus lamivudine or emtricitabine as the nucleoside reverse transcriptase inhibitor backbone in first-line regimens for HIV-infected adults. Lamivudine alone is not recommended, because of the risk of hepatitis B virus (HBV) resistance. We studied HBV responses in a large cohort of co-infected patients in a resource-limited setting.
Clinical centers in Uganda and Zimbabwe.
DART was a randomized trial of monitoring practices in HIV-infected adults starting antiretroviral therapy. Baseline samples were tested retrospectively for HBV serological markers and HBV DNA. Longitudinal HBV DNA testing at 48 weeks and the last available sample before HBV-relevant modification of antiretroviral therapy was performed on patients with detectable HBV DNA at baseline.
Two hundred twenty-four hepatitis B surface antigen-positive patients were followed for up to 4.8 years. Of the drugs with anti-HBV activity, 166 were prescribed lamivudine-tenofovir and 58 lamivudine alone. Ninety-eight percent (96/98) patients with baseline HBV DNA <6 log10 IU/mL achieved viral suppression at 48 weeks (HBV DNA <48 IU/mL), regardless of regimen, compared with 50%(26/52) for HBV DNA >6 log10 IU/mL. Of the 83 patients suppressed at 48 weeks and with follow-up data, only 7(8%) experienced viral rebound (range 200-3460 IU/mL). Of the 20 patients not suppressed at 48 weeks and with follow-up data, HBV DNA levels generally declined with lamivudine-tenofovir, but increased with lamivudine alone. Alanine transaminase flares were not observed in any patient who experienced viral rebound.
The suppressive effect of lamivudine alone was highly durable (up to 5 years) in HIV-HBV co-infected patients with baseline HBV DNA <6 log10 IU/mL. It may be feasible to develop stratified approaches using lamivudine as the only drug with anti-HBV activity.
世界卫生组织（WHO）治疗指南建议将替诺福韦加拉米夫定或恩曲他滨作为核苷逆转录酶抑制剂骨干用于治疗感染艾滋病毒的成人一线方案。由于乙型肝炎病毒（HBV）耐药的风险，不建议单独使用拉米夫定。我们在资源有限的环境中对大量合并感染患者进行了 HBV 反应研究。
乌干达和津巴布韦的临床中心。
DART 是一项评估 HIV 感染成人开始抗逆转录病毒治疗时监测实践的随机试验。对基线样本进行了回顾性 HBV 血清学标志物和 HBV DNA 检测。在基线时可检测到 HBV DNA 的患者中，在 48 周和最后一次可获得的 HBV 相关抗逆转录病毒治疗修改前的样本中进行了纵向 HBV DNA 检测。
224 例乙型肝炎表面抗原阳性患者接受了长达 4.8 年的随访。在具有抗 HBV 活性的药物中，166 例患者接受了拉米夫定-替诺福韦治疗，58 例患者单独接受了拉米夫定治疗。基线 HBV DNA<6 log10 IU/mL 的 98%（96/98）患者在 48 周时达到病毒抑制（HBV DNA<48 IU/mL），无论方案如何，与 HBV DNA>6 log10 IU/mL 的患者相比，这一比例为 50%（26/52）。在 48 周时被抑制且有随访数据的 83 例患者中，只有 7 例（8%）发生病毒反弹（范围为 200-3460 IU/mL）。在 20 例 48 周时未被抑制且有随访数据的患者中，HBV DNA 水平通常随着拉米夫定-替诺福韦的使用而下降，但随着拉米夫定的单独使用而增加。在发生病毒反弹的任何患者中均未观察到丙氨酸氨基转移酶爆发。
在基线 HBV DNA<6 log10 IU/mL 的 HIV-HBV 合并感染患者中，拉米夫定单独使用的抑制作用具有高度的持久性（长达 5 年）。使用拉米夫定作为唯一具有抗 HBV 活性的药物开发分层方法可能是可行的。
