Institute of Infection and Global Health, University of Liverpool, United Kingdom.
Department of Medicine, Kwame Nkrumah University of Science and Technology Komfo Anokye Teaching Hospital, Kumasi, Ghana.
Clin Infect Dis. 2015 Sep 15;61(6):883-91. doi: 10.1093/cid/civ421. Epub 2015 May 28.
Antiretroviral treatment (ART) programs in sub-Saharan Africa have for many years included lamivudine as the sole hepatitis B virus (HBV) inhibitor. Long-term outcomes and the effects of introducing tenofovir as part of ART in these populations have not been characterized.
The study comprised a cross-sectional analysis of 106 human immunodeficiency virus (HIV)/HBV-coinfected subjects maintained on lamivudine, as well as a prospective analysis of 76 lamivudine-experienced subjects who introduced tenofovir. Patients underwent assessment of liver fibrosis by transient elastography (TE) and testing to characterize HIV type 1 (HIV-1) and HBV replication.
After a median of 45 months of lamivudine treatment, HIV-1 RNA and HBV DNA were detectable in 35 of 106 (33.0%) and 54 of 106 (50.9%) subjects, respectively, with corresponding drug resistance rates of 17 of 106 (16.0%) and 31 of 106 (29.2%), respectively. Median TE values were 5.7 kPa (interquartile range, 4.7-7.2 kPa) and independently associated with HBV DNA load, aspartate aminotransferase levels, and platelet counts; 13 of 106 (12.3%) subjects had TE measurements >9.4 kPa. Twelve months after the first assessment, and a median of 7.8 months after introducing tenofovir, HBV DNA levels declined by a mean of 1.5 log10 IU/mL (P < .001). TE values changed by a mean of -0.2 kPa (P = .097), and declined significantly in subjects who had pretenofovir HBV DNA levels >2000 IU/mL (mean, -0.8 kPa; P = .048) or TE values >7.6 kPa (mean, -1.2 kPa; P = .021). HIV-1 RNA detection rates remained unchanged.
A proportion of HIV/HBV-coinfected patients on long-term lamivudine-containing ART had poor HIV and HBV suppression, drug resistance, and TE values indicative of advanced liver fibrosis. Tenofovir improved HBV control and reduced liver stiffness in subjects with high HBV DNA load and TE values.
撒哈拉以南非洲的抗逆转录病毒治疗 (ART) 项目多年来一直将拉米夫定为唯一的乙型肝炎病毒 (HBV) 抑制剂。在这些人群中，长期结局以及将替诺福韦作为 ART 的一部分引入的效果尚未得到描述。
本研究包括对 106 名接受拉米夫定治疗的人类免疫缺陷病毒 (HIV)/HBV 合并感染患者进行的横断面分析，以及对 76 名接受拉米夫定治疗的经验丰富的患者进行的前瞻性分析。患者接受瞬时弹性成像 (TE) 评估肝纤维化，并进行检测以确定 HIV-1 类型 (HIV-1) 和 HBV 复制。
在中位数为 45 个月的拉米夫定治疗后，106 名患者中的 35 名 (33.0%) 和 106 名中的 54 名 (50.9%) 分别可检测到 HIV-1 RNA 和 HBV DNA，相应的耐药率分别为 106 名中的 17 名 (16.0%) 和 106 名中的 31 名 (29.2%)。中位数 TE 值为 5.7 kPa(四分位距，4.7-7.2 kPa)，与 HBV DNA 载量、天冬氨酸氨基转移酶水平和血小板计数独立相关；106 名患者中有 13 名 (12.3%) 的 TE 测量值>9.4 kPa。首次评估后 12 个月，中位数在引入替诺福韦后 7.8 个月，HBV DNA 水平下降了平均 1.5 log10 IU/mL(P<0.001)。TE 值平均下降 0.2 kPa(P=0.097)，在替诺福韦前 HBV DNA 水平>2000 IU/mL(平均，-0.8 kPa；P=0.048)或 TE 值>7.6 kPa(平均，-1.2 kPa；P=0.021)的患者中显著下降。HIV-1 RNA 检出率保持不变。
长期接受含拉米夫定的 ART 治疗的 HIV/HBV 合并感染患者中，一部分患者 HIV 和 HBV 抑制效果不佳、耐药、TE 值提示存在晚期肝纤维化。替诺福韦改善了高 HBV DNA 载量和 TE 值患者的 HBV 控制并降低了肝硬度。
