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Abstract：
To determine the time to CD4 : CD8 ratio normalization among Canadian adults living with HIV in the modern ART era. To identify characteristics associated with ratio normalization.
Retrospective analysis of the Canadian Observational Cohort (CANOC), an interprovincial cohort of ART-naive adults living with HIV, recruited from 11 treatment centres across Canada. We studied participants initiating ART between 1 January 2011 and 31 December 2016 with baseline CD4 : CD8 ratio <1.0 and ≥2 follow-up measurements. Normalization was defined as two consecutive CD4 : CD8 ratios ≥1.0. Kaplan-Meier estimates and log-rank tests described time to normalization. Univariable and multivariable proportional hazards (PH) models identified factors associated with ratio normalization.
Among 3218 participants, 909 (28%) normalized during a median 2.6 years of follow-up. Participants with higher baseline CD4+ T-cell count were more likely to achieve normalization; the probability of normalization by 5 years was 0.68 (95% CI 0.62-0.74) for those with baseline CD4+ T-cell count >500 cells/mm3 compared with 0.16 (95% CI 0.11-0.21) for those with ≤200 cells/mm3 (P < 0.0001). In a multivariable PH model, baseline CD4+ T-cell count was associated with a higher likelihood of achieving ratio normalization (adjusted HR = 1.5, 95% CI 1.5-1.6 per 100 cells/mm3, P < 0.0001). After adjusting for baseline characteristics, time-dependent ART class was not associated with ratio normalization.
Early ART initiation, at higher baseline CD4+ T-cell counts, has the greatest impact on CD4 : CD8 ratio normalization. Our study supports current treatment guidelines recommending immediate ART start, with no difference in ratio normalization observed based on ART class used.
Retrospective analysis of the Canadian Observational Cohort (CANOC), an interprovincial cohort of ART-naive adults living with HIV, recruited from 11 treatment centres across Canada. We studied participants initiating ART between 1 January 2011 and 31 December 2016 with baseline CD4 : CD8 ratio <1.0 and ≥2 follow-up measurements. Normalization was defined as two consecutive CD4 : CD8 ratios ≥1.0. Kaplan-Meier estimates and log-rank tests described time to normalization. Univariable and multivariable proportional hazards (PH) models identified factors associated with ratio normalization.
Among 3218 participants, 909 (28%) normalized during a median 2.6 years of follow-up. Participants with higher baseline CD4+ T-cell count were more likely to achieve normalization; the probability of normalization by 5 years was 0.68 (95% CI 0.62-0.74) for those with baseline CD4+ T-cell count >500 cells/mm3 compared with 0.16 (95% CI 0.11-0.21) for those with ≤200 cells/mm3 (P < 0.0001). In a multivariable PH model, baseline CD4+ T-cell count was associated with a higher likelihood of achieving ratio normalization (adjusted HR = 1.5, 95% CI 1.5-1.6 per 100 cells/mm3, P < 0.0001). After adjusting for baseline characteristics, time-dependent ART class was not associated with ratio normalization.
Early ART initiation, at higher baseline CD4+ T-cell counts, has the greatest impact on CD4 : CD8 ratio normalization. Our study supports current treatment guidelines recommending immediate ART start, with no difference in ratio normalization observed based on ART class used.
摘要：
确定在现代ART时代，加拿大成年人感染HIV的CD4：CD8比值正常化的时间。识别与比率归一化相关的特征。
加拿大观察队列（CANOC）的回顾性分析，一个跨省队列的抗逆转录病毒成人感染艾滋病毒，从加拿大的11个治疗中心招募。我们研究了在2011年1月1日至2016年12月31日之间开始ART的参与者，基线CD4：CD8比率<1.0和≥2次随访测量。标准化定义为两个连续的CD4：CD8比率≥1.0。Kaplan-Meier估计和对数秩检验描述了归一化时间。单变量和多变量比例风险（PH）模型确定了与比率归一化相关的因素。
在3218名参与者中，909（28%）在中位2.6年的随访期间恢复正常。基线CD4+T细胞计数较高的参与者更有可能实现正常化；基线CD4+T细胞计数>500细胞/mm3的参与者5年正常化的概率为0.68（95％CI0.62-0.74），而≤200细胞/mm3的参与者为0.16（95％CI0.11-0.21）（P<0.0001）。在多变量PH模型中，基线CD4+T细胞计数与实现比值正常化的可能性较高相关(校正后HR=1.5,95%CI1.5-1.6/100细胞/mm3,P<0.0001).调整基线特性后，时间依赖性ART类别与比率正常化无关.
早期ART启动，在较高的基线CD4+T细胞计数，对CD4：CD8比值正常化的影响最大。我们的研究支持目前的治疗指南，建议立即开始ART，根据使用的ART类别观察到的比率归一化没有差异。
加拿大观察队列（CANOC）的回顾性分析，一个跨省队列的抗逆转录病毒成人感染艾滋病毒，从加拿大的11个治疗中心招募。我们研究了在2011年1月1日至2016年12月31日之间开始ART的参与者，基线CD4：CD8比率<1.0和≥2次随访测量。标准化定义为两个连续的CD4：CD8比率≥1.0。Kaplan-Meier估计和对数秩检验描述了归一化时间。单变量和多变量比例风险（PH）模型确定了与比率归一化相关的因素。
在3218名参与者中，909（28%）在中位2.6年的随访期间恢复正常。基线CD4+T细胞计数较高的参与者更有可能实现正常化；基线CD4+T细胞计数>500细胞/mm3的参与者5年正常化的概率为0.68（95％CI0.62-0.74），而≤200细胞/mm3的参与者为0.16（95％CI0.11-0.21）（P<0.0001）。在多变量PH模型中，基线CD4+T细胞计数与实现比值正常化的可能性较高相关(校正后HR=1.5,95%CI1.5-1.6/100细胞/mm3,P<0.0001).调整基线特性后，时间依赖性ART类别与比率正常化无关.
早期ART启动，在较高的基线CD4+T细胞计数，对CD4：CD8比值正常化的影响最大。我们的研究支持目前的治疗指南，建议立即开始ART，根据使用的ART类别观察到的比率归一化没有差异。
