Rodger Alison J, Sabin Caroline A
aResearch Department of Infection and Population Health, University College LondonbDepartment of Infectious Diseases, Royal Free London NHS Foundation Trust, London, UK.
Curr Opin HIV AIDS. 2016 Sep;11(5):487-491. doi: 10.1097/COH.0000000000000307.
Until recently, conflicting data led to discrepancies in guideline recommendation on 'when to start' antiretroviral therapy (ART) in asymptomatic HIV infection. This review focuses on evidence underpinning guidelines over the past decade and recent randomized clinical trial data in this area, which definitively informed the debate.
In 2015, the landmark START trial demonstrated clear clinical benefit in terms of a reduction in serious AIDS and non-AIDS-related events and death from any cause in HIV-positive individuals randomized to start ART with a CD4 count more than 500 cells/μl compared with deferring starting until CD4 count declined to 350 cells/μl. Further, randomized clinical trial data were also available from the Temprano trial in Côte D'Ivoire which also demonstrated a reduced risk of death associated with earlier ART initiation.
Following the results of the START trial, guidelines that had previously set CD4 thresholds for treatment initiation were universally changed. This is likely to reduce mortality in people living with HIV who are diagnosed early and have immediate access to ART. However, unless HIV testing rates and ART coverage are increased globally, raising the threshold for initiation of ART in clinical guidelines may be of limited benefit in reducing mortality in HIV.
直到最近,相互矛盾的数据导致在无症状HIV感染中启动抗逆转录病毒疗法(ART)的指南推荐存在差异。本综述聚焦于过去十年间支撑指南的证据以及该领域近期的随机临床试验数据,这些数据为相关辩论提供了明确依据。
2015年,具有里程碑意义的START试验表明,与推迟至CD4细胞计数降至350个/μl才开始治疗相比,随机分配接受ART治疗且CD4细胞计数超过500个/μl的HIV阳性个体,在减少严重艾滋病及非艾滋病相关事件以及任何原因导致的死亡方面具有明显的临床益处。此外,来自科特迪瓦的Temprano试验也有随机临床试验数据,该试验同样表明早期启动ART可降低死亡风险。
根据START试验的结果,此前设定治疗起始CD4阈值的指南已普遍更改。这可能会降低早期诊断并能立即获得ART治疗的HIV感染者的死亡率。然而,除非全球范围内提高HIV检测率和ART覆盖率,否则在临床指南中提高ART起始阈值对降低HIV死亡率的益处可能有限。