Cori Anne, Ayles Helen, Beyers Nulda, Schaap Ab, Floyd Sian, Sabapathy Kalpana, Eaton Jeffrey W, Hauck Katharina, Smith Peter, Griffith Sam, Moore Ayana, Donnell Deborah, Vermund Sten H, Fidler Sarah, Hayes Richard, Fraser Christophe
MRC Centre for Outbreak Analysis and Modelling, Department of Infectious Disease Epidemiology, Imperial College London, London, United Kingdom.
ZAMBART, University of Zambia, School of Medicine, Ridgeway Campus, Lusaka, Zambia ; Department of Clinical Research, London School of Hygiene and Tropical Medicine, London, United Kingdom.
PLoS One. 2014 Jan 15;9(1):e84511. doi: 10.1371/journal.pone.0084511. eCollection 2014.
The HPTN 052 trial confirmed that antiretroviral therapy (ART) can nearly eliminate HIV transmission from successfully treated HIV-infected individuals within couples. Here, we present the mathematical modeling used to inform the design and monitoring of a new trial aiming to test whether widespread provision of ART is feasible and can substantially reduce population-level HIV incidence.
The HPTN 071 (PopART) trial is a three-arm cluster-randomized trial of 21 large population clusters in Zambia and South Africa, starting in 2013. A combination prevention package including home-based voluntary testing and counseling, and ART for HIV positive individuals, will be delivered in arms A and B, with ART offered universally in arm A and according to national guidelines in arm B. Arm C will be the control arm. The primary endpoint is the cumulative three-year HIV incidence. We developed a mathematical model of heterosexual HIV transmission, informed by recent data on HIV-1 natural history. We focused on realistically modeling the intervention package. Parameters were calibrated to data previously collected in these communities and national surveillance data. We predict that, if targets are reached, HIV incidence over three years will drop by >60% in arm A and >25% in arm B, relative to arm C. The considerable uncertainty in the predicted reduction in incidence justifies the need for a trial. The main drivers of this uncertainty are possible community-level behavioral changes associated with the intervention, uptake of testing and treatment, as well as ART retention and adherence.
The HPTN 071 (PopART) trial intervention could reduce HIV population-level incidence by >60% over three years. This intervention could serve as a paradigm for national or supra-national implementation. Our analysis highlights the role mathematical modeling can play in trial development and monitoring, and more widely in evaluating the impact of treatment as prevention.
HPTN 052试验证实，抗逆转录病毒疗法（ART）几乎可以消除夫妻中成功接受治疗的HIV感染者的HIV传播。在此，我们介绍用于指导一项新试验的设计和监测的数学模型，该试验旨在测试广泛提供ART是否可行，以及是否能大幅降低人群层面的HIV发病率。
HPTN 071（PopART）试验是一项三臂整群随机试验，于2013年在赞比亚和南非的21个大型人群群组中开展。A组和B组将实施包括家庭自愿检测咨询以及为HIV阳性个体提供ART的综合预防方案，A组普遍提供ART，B组则根据国家指南提供。C组为对照组。主要终点是三年累计HIV发病率。我们基于近期关于HIV-1自然史的数据，开发了一个异性间HIV传播的数学模型。我们着重对干预方案进行实际建模。参数根据此前在这些社区收集的数据以及国家监测数据进行校准。我们预测，如果达到目标，相对于C组，A组三年的HIV发病率将下降超过60%，B组将下降超过25%。预测发病率下降幅度存在相当大的不确定性，这证明有必要进行一项试验。这种不确定性的主要驱动因素包括与干预相关的可能的社区层面行为变化、检测和治疗的接受情况，以及ART的留存率和依从性。
HPTN 071（PopART）试验干预措施可在三年内将人群层面的HIV发病率降低超过60%。该干预措施可作为国家或超国家层面实施的范例。我们的分析突出了数学模型在试验开发和监测中以及在更广泛地评估治疗即预防的影响方面所能发挥的作用。
