Cumulative Viral Load and Virologic Decay Patterns after Antiretroviral Therapy in HIV-Infected Subjects Influence CD4 Recovery and AIDS
Cumulative Viral Load and Virologic Decay Patterns after Antiretroviral Therapy in HIV-Infected Subjects Influence CD4 Recovery and AIDS
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DOI：
10.1371/journal.pone.0017956
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发表时间：
2011-05-20
期刊：
影响因子：
3.7
通讯作者：
Kulkarni, Hemant
中科院分区：
文献类型：
--
作者：
Marconi, Vincent C.;Grandits, Greg;Kulkarni, Hemant
背景：病毒载量(VL)衰减和累积VL对高效抗逆转录病毒治疗(HAART)后CD4恢复和艾滋病的影响尚不清楚。方法和结果：在美军HIV自然史研究中，对2,278名开始HAART的患者估计了三个病毒学动力学参数(第一年和总指数VL衰减常数和第一年VL斜率)和累积VL。使用线性和非线性广义估计方程模型计算CD4和VL轨迹。多变量泊松和线性回归模型被用来确定VL参数与CD4恢复之间的相关性，并根据已知与免疫恢复相关的因素进行了调整。累积VL高于样本中位数与艾滋病风险增加独立相关(相对危险度2.38，95%可信区间1.56-3.62，p<；0.001)。在VL抑制的患者中，第一年VL下降和斜率是CD_4早期恢复(p=0.001)和总体增加(p<；0.05)的独立预测因素。尽管VL受到抑制，但总体上，与其他受试者相比，在HAART的第一年和整个治疗期间，VL缓慢衰退的受试者获得的CD4细胞较少(133vs.195.4个细胞/亩L；p=0.001)，即使在调整了潜在的混杂因素后也是如此。结论：在一个免费获得医疗保健的队列中，与HAART期间艾滋病和CD4恢复的既定预测因素无关，VL的累积和病毒学衰退模式与艾滋病和CD4重建的不同方面有关。
Background: The impact of viral load (VL) decay and cumulative VL on CD4 recovery and AIDS after highly-active antiretroviral therapy (HAART) is unknown.Methods and Findings: Three virologic kinetic parameters (first year and overall exponential VL decay constants, and first year VL slope) and cumulative VL during HAART were estimated for 2,278 patients who initiated HAART in the U. S. Military HIV Natural History Study. CD4 and VL trajectories were computed using linear and nonlinear Generalized Estimating Equations models. Multivariate Poisson and linear regression models were used to determine associations of VL parameters with CD4 recovery, adjusted for factors known to correlate with immune recovery. Cumulative VL higher than the sample median was independently associated with an increased risk of AIDS (relative risk 2.38, 95% confidence interval 1.56-3.62, p < 0.001). Among patients with VL suppression, first year VL decay and slope were independent predictors of early CD4 recovery (p = 0.001) and overall gain (p < 0.05). Despite VL suppression, those with slow decay during the first year of HAART as well as during the entire therapy period (overall), in general, gained less CD4 cells compared to the other subjects (133 vs. 195.4 cells/mu L; p = 0.001) even after adjusting for potential confounders.Conclusions: In a cohort with free access to healthcare, independent of established predictors of AIDS and CD4 recovery during HAART, cumulative VL and virologic decay patterns were associated with AIDS and distinct aspects of CD4 reconstitution.