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男男性行为者中的检测与治疗覆盖率及HIV毒力演变

Test-and-treat coverage and HIV virulence evolution among men who have sex with men.

作者信息

Stansfield Sarah E, Herbeck Joshua T, Gottlieb Geoffrey S, Abernethy Neil F, Murphy James T, Mittler John E, Goodreau Steven M

机构信息

Department of Biomedical Informatics and Medical Education, University of Washington, Seattle, WA 98195, USA.

Department of Global Health, University of Washington, Seattle, WA 98195, USA.

出版信息

Virus Evol. 2021 Feb 10;7(1):veab011. doi: 10.1093/ve/veab011. eCollection 2021 Jan.

Abstract

HIV set point viral load (SPVL), the viral load established shortly after initial infection, is a proxy for HIV virulence: higher SPVLs lead to higher risk of transmission and faster disease progression. Three models of test-and-treat scenarios, mainly in heterosexual populations, found that increasing treatment coverage selected for more virulent viruses. We modeled virulence evolution in a population of men who have sex with men (MSM) with increasing test-and-treat coverage. We extended a stochastic, dynamic network model (EvoNetHIV). We varied relationship patterns (MSM vs. heterosexual), HIV transmission models (increasing vs. plateauing probability of transmission at very high viral loads), and treatment roll-out (with explicit testing or fixed intervals between infection and treatment). In scenarios most similar to previous models (longer relational durations and the plateauing transmission function), we replicated trends previously found: increasing treatment coverage led to increased virulence (0.12 log increase in mean population SPVL between 20% and 100% treatment coverage). In scenarios reflecting MSM behavioral data using the increasing transmission function, increasing treatment coverage selected for viruses with virulence (0.16 log decrease in mean population SPVL between 20% and 100% treatment coverage). These findings emphasize the impact of sexual network conditions and transmission function details on predicted epidemiological and evolutionary outcomes. Varying these features creates very different evolutionary environments, which in turn lead to opposite effects in mean population SPVL evolution. Our results suggest that, under some realistic conditions, effective test-and-treat strategies may face the previously reported tradeoff in which increasing coverage leads to evolution of greater virulence. This suggests instead that a virtuous cycle of increasing treatment coverage and diminishing virulence is possible.

摘要

HIV设定点病毒载量(SPVL)是初次感染后不久确立的病毒载量,可作为HIV毒力的替代指标:较高的SPVL会导致更高的传播风险和更快的疾病进展。三种主要针对异性恋人群的检测与治疗方案模型发现,扩大治疗覆盖范围会筛选出毒性更强的病毒。我们对男男性行为者(MSM)群体中随着检测与治疗覆盖范围扩大的毒力进化进行了建模。我们扩展了一个随机动态网络模型(EvoNetHIV)。我们改变了关系模式(男男性行为者与异性恋)、HIV传播模型(在病毒载量非常高时传播概率增加或趋于平稳)以及治疗推广方式(有明确检测或感染与治疗之间固定间隔)。在与之前模型最相似的情景中(关系持续时间更长和平稳传播函数),我们重现了之前发现的趋势:扩大治疗覆盖范围会导致毒力增加(治疗覆盖范围从20%提高到100%时,平均群体SPVL增加0.12个对数)。在使用增加传播函数反映男男性行为者行为数据的情景中,扩大治疗覆盖范围筛选出了毒力较低的病毒(治疗覆盖范围从20%提高到100%时,平均群体SPVL减少0.16个对数)。这些发现强调了性网络状况和传播函数细节对预测的流行病学和进化结果的影响。改变这些特征会创造出非常不同的进化环境,进而在平均群体SPVL进化中产生相反的效果。我们的结果表明,在某些现实条件下,有效的检测与治疗策略可能会面临之前报道的权衡,即扩大覆盖范围会导致更强毒力的进化。相反,这表明扩大治疗覆盖范围和降低毒力的良性循环是可能的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/859e/7893213/ed26c246383c/veab011f1.jpg

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