AIDS Research Center, VA Palo Alto Health Care System, Palo Alto, California 94304, USA.
J Med Virol. 2010 May;82(5):791-8. doi: 10.1002/jmv.21679.
Many hepatitis C virus (HCV)-infected patients are also infected with HIV, and undergo antiretroviral (ARV) treatment for their human immunodeficiency virus (HIV) infection. Due to changes in HIV burden and immunologic status, HIV ARV treatment may have indirect effects on the HCV population, which could impact the effectiveness of subsequent HCV protease inhibitor (PI) treatment. The genetic variability of the protease-encoding HCV NS3 gene was evaluated in 10 co-infected patients initiating ARVs (both before and after ARV initiation), and compared to the genetic variability in 10 patients on stable ARV therapy. After RT-PCR of plasma-derived HCV RNA, a mean of 20 clones per patient time-point were sequenced and analyzed for changes in the HCV quasispecies population. No significant differences in sequence diversity or complexity at the nucleic acid or amino acid levels were seen at baseline between groups or between the two time points in either group. HCV protease diversity in the pre- and post-ARV treatment samples was not significantly different than samples from patients on stable ARV therapy. There was no significant development of amino acid substitutions known to confer HCV PI resistance in either group. Initiation of ARV for HIV infection does not significantly alter the genetic diversity or complexity of the HCV NS3 gene or result in increased number of HCV PI-associated amino acid changes. These results suggest ARV treatment for HIV would not affect the efficacy of HCV PI treatment.
许多丙型肝炎病毒（HCV）感染的患者同时也感染了人类免疫缺陷病毒（HIV），并接受抗逆转录病毒（ARV）治疗以控制其 HIV 感染。由于 HIV 负担和免疫状态的变化，HIV ARV 治疗可能对 HCV 人群产生间接影响，从而影响随后的 HCV 蛋白酶抑制剂（PI）治疗的效果。在开始接受 ARV 治疗的 10 例合并感染患者（在开始 ARV 治疗之前和之后）中，评估了编码 HCV NS3 基因的蛋白酶的遗传变异性，并与 10 例接受稳定 ARV 治疗的患者的遗传变异性进行了比较。对源自血浆的 HCV RNA 进行 RT-PCR 后，对每个患者时间点的平均 20 个克隆进行测序，并分析 HCV 准种群体的变化。在基线时，各组之间或两组内的任何时间点在核酸或氨基酸水平上均未观察到序列多样性或复杂性的显著差异。在 ARV 治疗前和治疗后的样本中，HCV 蛋白酶的多样性与接受稳定 ARV 治疗的患者的样本没有显著差异。两组中均未发现明显导致 HCV PI 耐药的氨基酸取代。启动针对 HIV 感染的 ARV 治疗不会显著改变 HCV NS3 基因的遗传多样性或复杂性，也不会导致 HCV PI 相关氨基酸变化的数量增加。这些结果表明，针对 HIV 的 ARV 治疗不会影响 HCV PI 治疗的疗效。
