Cumulative Viral Load and Virologic Decay Patterns after Antiretroviral Therapy in HIV-Infected Subjects Influence CD4 Recovery and AIDS

BackgroundThe impact of viral load (VL) decay and cumulative VL on CD4 recovery and AIDS after highly-active antiretroviral therapy (HAART) is unknown. Methods and FindingsThree 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 ConclusionsIn 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.

背景：高效抗反转录病毒治疗（highly-active antiretroviral therapy, HAART）后，病毒载量（viral load, VL）衰变与累积病毒载量对CD4细胞恢复及艾滋病（AIDS）发生的影响尚不明确。方法与结果：美国军事HIV自然史研究纳入2278例启动HAART治疗的患者，对其3项病毒动力学参数（治疗首年及总体的VL指数衰变常数、首年VL变化斜率）及HAART治疗期间的累积VL进行估算。采用线性与非线性广义估计方程（Generalized Estimating Equations）模型计算CD4细胞及VL的变化轨迹；通过多变量泊松回归与线性回归模型，在校正已知与免疫恢复相关的混杂因素后，分析VL参数与CD4细胞恢复的相关性。结果显示，高于样本中位数的累积VL与艾滋病发病风险升高独立相关（相对风险2.38，95%置信区间1.56~3.62，p）。结论：在可免费获取医疗服务的队列中，在排除已明确的HAART治疗期间艾滋病及CD4细胞恢复预测因素的影响后，累积VL与病毒学衰变模式与艾滋病发生及CD4细胞重建的特定方面存在关联。