人类免疫缺陷病毒感染/艾滋病患者抗反转录病毒治疗后的低病毒血症对治疗效果的影响

Impact of low level viremia on the antiviral effect of human immunodeficiency virus/acquired immunodeficiency syndrome patients received anti-retroviral therapy

目的探讨人类免疫缺陷病毒(human immunodeficiency virus,HIV)感染/艾滋病患者接受抗反转录病毒治疗(anti-retroviral therapy,ART)后发生低病毒血症(low level viremia,LLV)对其治疗预后的影响。方法纳入2015年1月至12月在广州医科大学附属市八医院感染门诊接受ART≥1年且存在LLV的HIV感染/艾滋病患者(LLV组),根据性别、年龄、传播途径1∶1匹配血浆HIV-1 RNA<50拷贝/mL的患者为对照组(抑制组)。根据病毒载量将LLV组分成3个亚组,其中LLV-1亚组指HIV-1 RNA为50~200拷贝/mL,LLV-2亚组指HIV-1 RNA为201~400拷贝/mL,LLV-3亚组指HIV-1 RNA为401~1000拷贝/mL。分析LLV对后续3年抗病毒治疗应答的影响。统计学分析采用威尔科克森符号秩检验、Kruskal-Wallis检验和χ^(2)检验。结果LLV组共纳入137例患者,其中男111例,女26例,年龄为(39.5±13.5)岁。同时抑制组纳入137例患者。LLV-1、LLV-2和LLV-3亚组分别为93、25和19例。LLV组和抑制组ART前CD4^(+)T淋巴细胞计数与CD4^(+)T淋巴细胞计数/CD8^(+)T淋巴细胞计数比值差异均无统计学意义(均P>0.05)。随访3年,LLV组累计发生病毒学失败患者比例[7.3%(10/137)]高于抑制组[1.5%(2/137)],差异有统计学意义(χ^(2)=5.578,P=0.018);LLV-1、LLV-2和LLV-3亚组分别有8例(8.6%)、2例(8.0%)和0例发生病毒学失败,各亚组病毒学失败发生率差异无统计学意义(P>0.05)。LLV组和抑制组在随访1、2、3年时的CD4^(+)T淋巴细胞计数差异均无统计学意义(均P>0.05),LLV组在随访1、2、3年时的CD4^(+)T淋巴细胞计数/CD8^(+)T淋巴细胞计数比值均低于抑制组,差异均有统计学意义(Z=-3.183、-2.094、-2.312,均P<0.05)。LLV-1、LLV-2和LLV-3亚组的CD4^(+)T淋巴细胞计数/CD8^(+)T淋巴细胞计数比值在随访1、2、3年时的差异均无统计学意义(均P>0.05)。结论ART超过1年存在LLV的HIV感染者/艾滋病患者更易发生病毒学失败,且免疫功能恢复减慢,提示需对其尽早给予干预。

Objective To investigate the impact of low level viremia(LLV)on the prognosis of human immunodeficiency virus(HIV)/acquired immunodeficiency syndrome(AIDS)patients received anti-retroviral therapy(ART).Methods From January to December 2015,the HIV/AIDS patients with LLV received ART over one year were recruited in Guangzhou Eighth People′s Hospital,Guangzhou Medical University(LLV group).Patients with viral load(VL)less than 50 copies/mL were matched at ratio of 1∶1 according to gender,age and the transmission route were included in the control group(suppression group).The LLV group was divided into three subgroups according to VL(LLV-1 subgroup was 50-200 copies/mL,LLV-2 subgroup was 201-400 copies/mL,and LLV-3 subgroup was 401-1000 copies/mL).The influence of LLV on the antiviral response during the following three years was investigated.The Wilcoxon signed rank test,Kruskal-Wallis test and chi-square test were used for statistical analysis.Results One hundred and thirty-seven patients were enrolled in the LLV group,of whom 111 were males and 26 were females,with age of(39.5±13.5)years old.At the same time,137 patients were included in the suppression group.There were 93 cases in LLV-1 subgroup,25 cases in LLV-2 subgroup and 19 cases in LLV-3 subgroup.There were no significant differences in the CD4^(+)T lymphocyte counts and CD4^(+)/CD8^(+)T lymphocyte counts ratios between LLV group and suppression group before ART(both P>0.05).During the three-year follow-up,the cumulative number of viral failures in LLV group(7.3%(10/137))was significantly higher than that in the suppression group(1.5%(2/137))(χ^(2)=5.578,P=0.018).Virological failure occurred in eight patients(8.6%)in the LLV-1 subgroup,two patients(8.0%)in the LLV-2 subgroup,and no patients in the LLV-3 subgroup.There was no statistical significance in the incidence of virological failure among all the subgroups(P>0.05).At one,two,three years follow-up,the CD4^(+)T lymphocyte counts increased in both LLV group and suppression group without statistical differences(all P>0.05),and the CD4^(+)/CD8^(+)T lymphocyte counts ratios in each LLV group were lower than that in the suppression group(Z=-3.183,-2.094 and-2.312,respectively,all P<0.05).At one,two,three years follow-up,There were no significant differences in CD4^(+)/CD8^(+)T lymphocyte counts ratios among the LLV-1,LLV-2 and LLV-3 subgroups(all P>0.05).Conclusion HIV/AIDS patients with LLV having received ART over one year are more likely to develop virological failure and delay the recovery of immune function,which requires early relevant interventions.