Background

Many mathematical models have investigated the population-level impact of expanding antiretroviral therapy (ART), using different assumptions about HIV disease progression on ART and among ART dropouts. We evaluated the influence of these assumptions on model projections of the number of infections and deaths prevented by expanded ART.

Methods

A new dynamic model of HIV transmission among men who have sex with men (MSM) was developed, which incorporated each of four alternative assumptions about disease progression used in previous models: (A) ART slows disease progression; (B) ART halts disease progression; (C) ART reverses disease progression by increasing CD4 count; (D) ART reverses disease progression, but disease progresses rapidly once treatment is stopped. The model was independently calibrated to HIV prevalence and ART coverage data from the United States under each progression assumption in turn. New HIV infections and HIV-related deaths averted over 10 years were compared for fixed ART coverage increases.

Results

Little absolute difference (<7 percentage points (pp)) in HIV infections averted over 10 years was seen between progression assumptions for the same increases in ART coverage (varied between 33% and 90%) if ART dropouts reinitiated ART at the same rate as ART-naïve MSM. Larger differences in the predicted fraction of HIV-related deaths averted were observed (up to 15pp). However, if ART dropouts could only reinitiate ART at CD4<200 cells/μl, assumption C predicted substantially larger fractions of HIV infections and deaths averted than other assumptions (up to 20pp and 37pp larger, respectively).

Conclusion

Different disease progression assumptions on and post-ART interruption did not affect the fraction of HIV infections averted with expanded ART, unless ART dropouts only re-initiated ART at low CD4 counts. Different disease progression assumptions had a larger influence on the fraction of HIV-related deaths averted with expanded ART.

中文翻译：

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在开始或停止治疗后关于HIV疾病进展的模型假设对扩大抗逆转录病毒疗法避免的感染和死亡估计的影响

背景

许多数学模型使用关于HIV疾病进展对ART以及ART辍学者的不同假设，研究了扩大抗逆转录病毒疗法（ART）的人口水平影响。我们评估了这些假设对扩大抗逆转录病毒疗法预防感染和死亡人数的模型预测的影响。

方法

建立了一种新的艾滋病病毒在男男性行为者之间传播的动态模型（MSM），该模型结合了先前模型中使用的关于疾病进展的四个备选假设中的每一个：（B）ART阻止疾病进展；（C）ART通过增加CD4计数来逆转疾病进展；（D）ART逆转疾病进展，但是一旦停止治疗，疾病会迅速进展。在每个进展假设下，根据美国的HIV流行率和ART覆盖率数据对模型进行了独立校准。比较了10年内避免的新的HIV感染和与HIV相关的死亡，以固定的ART覆盖率增加。

结果

如果ART辍学率以与ART覆盖率相同的比率重新开始，那么在ART覆盖率相同增长（介于33​​％和90％之间）的进展假设之间，在10年内避免的HIV感染中几乎没有绝对差异（<7个百分点（pp））。天真无味的MSM。观察到与艾滋病毒相关的死亡的预测比例所避免的较大差异（最高15pp）。但是，如果ART辍学只能以CD4 <200细胞/μl的速度重新启动ART，则假设C预测的HIV感染和死亡比例要比其他假设大得多（分别高达20pp和37pp）。

结论

除非抗病毒治疗仅在低CD4计数下重新开始抗病毒治疗，否则在抗病毒治疗和抗病毒治疗后不同的疾病进展假设下，均不会影响HIV感染因扩大抗病毒治疗而减少的比例。不同的疾病进展假设对扩大抗逆转录病毒疗法避免的艾滋病毒相关死亡比例影响更大。