Data from: Early antiretroviral therapy and potent second-line drugs could decrease HIV incidence of drug resistance

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 modeled 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 the second-line drug effectiveness is sufficiently high ($>$80\%), but increase the proportion of new infections that are drug resistant. Thus, resistance may paradoxically appear to be increasing while actually decreasing.抗逆转录病毒疗法（antiretroviral therapy, ART）早期启动可降低药物敏感性人类免疫缺陷病毒（human immunodeficiency virus, HIV）传播风险，但可能增加耐药HIV的传播概率。本研究借助数学模型评估了ART在人群层面的长期获益，并明确了在何种场景下，早期启动ART（平均于感染后1年启动治疗）可同时降低总HIV新发感染与耐药HIV新发感染的病例数。本研究构建了以感染时长为结构维度的数学模型，追踪感染全程中的传播速率，并将患者预期寿命建模为ART启动时机的函数。本研究将该模型直接拟合至旧金山男男性行为者（men who have sex with men, MSM）的年度艾滋病（acquired immunodeficiency syndrome, AIDS）新发感染与死亡数据，并间接拟合其耐药数据与人口统计学数据。通过构建反事实情景，本研究评估了ART启动时机、获得性耐药发生频率以及二线药物有效性（定义为耐药监测、生物医学药物疗效与依从性的综合指标）对总HIV新发感染与耐药HIV新发感染病例数的影响。当二线药物有效性足够高（>80%）时，更早启动ART可同时降低总HIV新发感染与耐药HIV新发感染的病例数，但会升高新发感染中耐药毒株所占的比例。因此，耐药性可能会呈现出看似上升实则下降的矛盾现象。