Thornhill John, Inshaw Jamie, Kaleebu Pontiano, Cooper David, Ramjee Gita, Schechter Mauro, Tambussi Giuseppe, Fox Julie, Samuel Miriam, Miro Jose M, Weber Jonathan, Porter Kholoud, Fidler Sarah
*Department of Medicine, Imperial College, London, United Kingdom; †Medical Research Council Clinical Trials Unit, University College London, London, United Kingdom; ‡Medical Research Council/Uganda Virus Research Institute Research Unit on AIDS, Entebbe, Uganda; §Kirby Institute University of New South Wales and Centre for Applied Medical Research, St Vincent's Hospital, Sydney, Australia; ‖HIV Prevention Unit, Medical Research Council, Durban, South Africa; ¶Projeto Praça Onze, Hospital Escola Sao Francisco de Assis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil; #Division of Infectious Diseases, Ospedale San Raffaele, Milan, Italy; **Department of HIV, Faculty of Medicine, Guys and St Thomas' NHS Trust/Kings College London, United Kingdom; and ††Hospital Clinic - IDIBAPS, University of Barcelona, Barcelona, Spain.
J Acquir Immune Defic Syndr. 2016 Sep 1;73(1):69-73. doi: 10.1097/QAI.0000000000001013.
Total CD4 T-cell counts predict HIV disease progression but do not necessarily reflect normalization of immune function. CD4/CD8 ratio is a marker of immune dysfunction, a prognostic indicator for non-AIDS mortality, and reflects viral reservoir size. Despite antiretroviral therapy (ART), recovery of CD4/CD8 ratio in chronic HIV infection is incomplete; we hypothesize enhanced CD4/CD8 ratio recovery with earlier treatment initiation in recently infected individuals.
CD4 count and CD4/CD8 ratio were analyzed using data from 2 cohorts: SPARTAC trial and the UK HIV Seroconverters Cohort where primary HIV infection (PHI) was defined as within 6 months from estimated date of infection. Using time-to-event methods and Cox proportional hazard models, we examined the effect of CD4/CD8 ratio at seroconversion on disease progression (CD4 <350 cells per cubic millimeter/ART initiation) and factors associated with time from ART initiation to CD4/CD8 normalization (ratio >1.0).
Of 573 seroconverters, 482 (84%) had abnormal CD4/CD8 ratios at HIV seroconversion. Individuals with higher CD4/CD8 ratio at seroconversion were significantly less likely to reach the disease progression endpoint [adjusted hazard ratio (aHR) (95% CI) = 0.52 (0.32 to 0.82), P = 0.005]. The longer the interval between seroconversion and ART initiation [HR (95% CI) = 0.98 per month increase (0.97, 0.99), P < 0.001], the less likely the CD4/CD8 ratio normalization. ART initiation within 6 months from seroconversion was significantly more likely to normalize [HR (95% CI) = 2.47 (1.67 to 3.67), P < 0.001] than those initiating later.
Most individuals presenting in PHI have abnormal CD4/CD8 ratios. The sooner the ART is initiated in PHI, the greater the probability of achieving normal CD4/CD8 ratio.
总CD4 T细胞计数可预测HIV疾病进展，但不一定反映免疫功能的正常化。CD4/CD8比值是免疫功能障碍的标志物、非艾滋病死亡率的预后指标，且反映病毒储存库大小。尽管有抗逆转录病毒疗法（ART），慢性HIV感染中CD4/CD8比值的恢复并不完全；我们假设在近期感染个体中更早开始治疗可增强CD4/CD8比值的恢复。
使用来自2个队列的数据分析CD4计数和CD4/CD8比值：SPARTAC试验和英国HIV血清转化者队列，其中原发性HIV感染（PHI）定义为距估计感染日期6个月内。使用事件发生时间方法和Cox比例风险模型，我们研究了血清转化时CD4/CD8比值对疾病进展（CD4<350个细胞/立方毫米/开始ART）的影响以及与从开始ART到CD4/CD8正常化（比值>1.0）的时间相关的因素。
在573名血清转化者中，482名（84%）在HIV血清转化时CD4/CD8比值异常。血清转化时CD4/CD8比值较高的个体达到疾病进展终点的可能性显著降低[调整后风险比（aHR）（95%CI）=0.52（0.32至0.82），P=0.005]。血清转化与开始ART之间的间隔时间越长[HR（95%CI）=每月增加0.98（0.97，0.99），P<0.001]，CD4/CD8比值正常化的可能性越小。血清转化后6个月内开始ART比之后开始ART更有可能实现正常化[HR（95%CI）=2.47（1.67至3.67），P<0.001]。
大多数表现为原发性HIV感染的个体CD4/CD8比值异常。原发性HIV感染中开始ART越早，实现CD4/CD8比值正常的可能性越大。
