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 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.抗逆转录病毒治疗（antiretroviral therapy, ART）的早期启动，可降低药物敏感性HIV传播风险，但可能会增加耐药HIV的传播概率。本研究采用数学模型，评估ART长期的人群层面获益，并明确在何种场景下，早期ART（即平均于感染后1年启动治疗）可同时降低总体HIV发病率与耐药HIV发病率（即新发感染数）。我们构建了感染年龄分层的数学模型，追踪感染全程中的传播速率，并将患者的预期寿命建模为ART启动时机的函数。我们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）的年度艾滋病发病率与死亡数据，并间接拟合其耐药数据与人口统计数据。通过构建反事实场景，我们评估了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用药依从性的综合指标）对总体HIV发病率与耐药HIV发病率的影响。当二线药物有效性足够高（大于80%）时，早期ART启动可同时降低总体HIV与耐药HIV的新发感染数，但会提升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。