Poor initial CD4+ recovery with antiretroviral therapy prolongs immune depletion and increases risk for AIDS and non-AIDS diseases.
Poor initial CD4+ recovery with antiretroviral therapy prolongs immune depletion and increases risk for AIDS and non-AIDS diseases.
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DOI：
10.1097/qai.0b013e31817bebb3
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发表时间：
2008-08-15
期刊：
影响因子：
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通讯作者：
Terry Beirn Community Programs for Clinical Research on AIDS (CPCRA)
中科院分区：
文献类型：
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作者：
Baker JV;Peng G;Rapkin J;Krason D;Reilly C;Cavert WP;Abrams DI;MacArthur RD;Henry K;Neaton JD;Terry Beirn Community Programs for Clinical Research on AIDS (CPCRA)
低CD4+会增加艾滋病和非艾滋病相关发病率和死亡率的风险。在最初的抗逆转录病毒治疗(ART)后早期，CD4+恢复的幅度在免疫衰竭的最终持续时间中是重要的。我们在8个月的初始ART中检测了850名参与艾滋病灵活初始逆转录病毒抑制疗法(即达到HIV RNA水平400拷贝/毫升)的艾滋病临床研究社区项目参与者的CD4+恢复情况，并在中位数5年随访中用COX回归分析确定了艾滋病、非艾滋病疾病(非艾滋病癌症和心血管疾病、终末期肾脏疾病和肝脏疾病)或死亡的风险。治疗前平均CD_4~+为221Cells/μL；18%(n=149)在有效ART治疗8个月后CD_4~+恢复较差(<；50个/μL)，导致5年内CD_4~+降低。年龄较大(风险比1.34/10岁，P=0.003)和筛查HIV RNA较低(风险比每对数10拷贝/毫升高0.65，P=0.001)，但没有筛查CD_4+，与CD_4+恢复较差有关。在有效的抗逆转录病毒治疗8个月后，30名患者经历了艾滋病、非艾滋病或死亡的综合结果，其中CD_4+恢复较差的参与者(比率=5.8百人年)和恢复良好的患者中的74人(≥50细胞/μL；比率=2.7百人年)(调整后的危险比=2.24P<；0.001)。当以较高的CD4+细胞计数开始抗逆转录病毒治疗时，与较差的CD4+恢复相关的综合结果的风险降低(P<；0.01)。免疫恢复受损，尽管抗逆转录病毒疗法有效，但会导致在低CD4+状态下停留更长的时间，从而增加一系列与艾滋病毒相关的发病率和死亡率的风险。
Low CD4+ increases risk for both AIDS- and non–AIDS-related morbidity and mortality. The magnitude of CD4+ recovery early after initial antiretroviral therapy (ART) is important in the ultimate duration of immune depletion. We examined CD4+ recovery among 850 participants in the Community Program for Clinical Research on AIDS Flexible Initial Retrovirus Suppressive Therapies study with virologic suppression (ie, achieved an HIV RNA level <400 copies/mL) with 8 months of initial ART and determined subsequent risk for AIDS, non-AIDS diseases (non-AIDS cancers and cardiovascular, end-stage renal, and liver diseases), or death using Cox regression during a median 5-year follow-up. Mean pretreatment CD4+ was 221 cells/μL; 18% (n = 149) had a poor CD4+ recovery (<50 cells/μL) after 8 months of effective ART, resulting in lower CD4+ over 5 years. Older age (hazard ratio 1.34/10 yrs, P = 0.003) and lower screening HIV RNA (hazard ratio 0.65 per log10 copies/mL higher, P = 0.001), but not screening CD4+, were associated with a poor CD4+ recovery. After 8 months of effective ART, 30 patients experienced the composite outcome of AIDS, non-AIDS, or death among participants with a poor CD4+ recovery (rate = 5.8/100 person-years) and 74 patients among those with an adequate recovery (≥50 cells/μL; rate = 2.7/100 personyears) (adjusted hazard ratio = 2.24, P < 0.001). The risk of this composite outcome associated with a poor CD4+ recovery declined when ART was initiated at higher CD4+ counts (P < 0.01). Impaired immune recovery, despite effective ART, results in longer time spent at low CD4+, thereby increasing risk for a broad category of HIV-related morbidity and mortality conditions.