Shen Mingwang, Xiao Yanni, Rong Libin, Meyers Lauren Ancel, Bellan Steven E
School of Mathematics and Statistics, Xi'an Jiaotong University, Xi'an 710049, People's Republic of China.
Department of Integrative Biology, The University of Texas at Austin, Austin, TX 78712, USA.
Proc Biol Sci. 2017 Jun 28;284(1857). doi: 10.1098/rspb.2017.0525.
Early initiation of antiretroviral therapy (ART) reduces the risk of drug-sensitive HIV transmission but may increase the transmission of drug-resistant HIV. We used a mathematical model to estimate the long-term population-level benefits of ART and determine the scenarios under which earlier ART (treatment at 1 year post-infection, on average) could decrease simultaneously both total and drug-resistant HIV incidence (new infections). We constructed an infection-age-structured mathematical model that tracked the transmission rates over the course of infection and modelled the patients' life expectancy as a function of ART initiation timing. We fitted this model to the annual AIDS incidence and death data directly, and to resistance data and demographic data indirectly among men who have sex with men (MSM) in San Francisco. Using counterfactual scenarios, we assessed the impact on total and drug-resistant HIV incidence of ART initiation timing, frequency of acquired drug resistance, and second-line drug effectiveness (defined as the combination of resistance monitoring, biomedical drug efficacy and adherence). Earlier ART initiation could decrease the number of both total and drug-resistant HIV incidence when second-line drug effectiveness is sufficiently high (greater than 80%), but increase the proportion of new infections that are drug resistant. Thus, resistance may paradoxically appear to be increasing while actually decreasing.
早期开始抗逆转录病毒疗法（ART）可降低对药物敏感的HIV传播风险，但可能会增加耐药HIV的传播。我们使用数学模型来估计ART的长期人群水平效益，并确定在哪些情况下更早开始ART（平均在感染后1年进行治疗）可同时降低总的和耐药HIV的发病率（新感染病例）。我们构建了一个感染年龄结构的数学模型，该模型追踪感染过程中的传播率，并将患者的预期寿命建模为ART开始时间的函数。我们将此模型直接拟合到旧金山男男性行为者（MSM）的年度艾滋病发病率和死亡数据，并间接拟合到耐药数据和人口统计数据。使用反事实情景，我们评估了ART开始时间、获得性耐药频率和二线药物有效性（定义为耐药监测、生物医学药物疗效和依从性的综合）对总的和耐药HIV发病率的影响。当二线药物有效性足够高（大于80%）时，更早开始ART可降低总的和耐药HIV的发病数量，但会增加耐药新感染病例的比例。因此，耐药情况可能看似在增加，而实际上却在减少。
